By Matt Butler, Cameron Watson, Ally Rooney, Jia Song, Jamie Badenoch, Ben Cross, Danish Hafeez, Mao Fong Lim, Hamilton Morrin, Emma Rengasamy, Lucretia Thomas, Sylvia Ralovska, Ritika Sundaram, Sujoy Ray, Vanshika Singh, Isabella Conti, Samyak Pandey, Arina Tamborska, Stuti Chakraborty, Zain Hussain, Susannah Pick, Katie Pocock, Aman Saini, Stanimir Neroev, Ella Burchill, Christopher Lucas, Olivia Morrow, Earl Aniwattanapong, Dean Walton, Jonathan Rogers, Ivan Koychev, Mark Ellul, Tom Solomon, Tom Pollak, Benedict Michael and Tim Nicholson
Evidence on the neurological and neuropsychiatric manifestations and complications of COVID-19 infections is emerging and this is likely to accelerate as the pandemic develops and clinical syndromes are detected, characterised and their mechanisms investigated.
In this blog we will:
- Collate relevant publications in a database using specified search strategies (including preprint servers).
- Analyse the evolving evidence base to highlight the key papers.
- Provide weekly updates including a brief digest of new publications, every Tuesday.
We will add other reporting systems as and when they are developed.
Highlights for 28th April – 4th May
This week’s blog marks a full year since the first iteration of our blog, which was published back when the pandemic was in its earliest stages and the literature was relatively sparse. In the intervening year, we have expanded to a large team of international clinical neuroscience experts, from junior to senior levels, who all devote some of their free time each week to preparing and disseminating this blog. In publishing this blog each week, we’ve learnt a huge amount about the neurology and neuropsychiatry of covid-19, and we hope that some of what we have learnt has been transmitted to the wider scientific community.
To mark this occasion, we bring you some exciting news. Over the coming weeks, the blog will be migrated to a new platform on a shiny new website! We will continue to be affiliated with the Journal of Neurology, Neurosurgery & Psychiatry, who have been consistently supportive of this endeavour from the off. We would like to extend a particular thanks to the ongoing work of Caitlin Alder at the BMJ, who is responsible each week for ensuring that the information is uploaded to the site on time. Not an easy task!
Our reasons for moving to a new site are, principally, twofold: a) we have quite simply outgrown the capability of the blog platform, and the huge amount of information now contained in the blog is making it a little wobbly at times, and b) we would like to include new functionality, such as searchable tables which will allow those interested to more easy delve into the repository of papers which constitute this blog. Watch this space!
Thank you to everyone reading for your ongoing support. Please keep an eye out over the next few weeks for more announcements about the blog migration. Until then, we will continue to update this blog on a weekly basis.
This week we have summarised 71 papers on the neurology and neuropsychiatry of COVID-19.
Computerised CBT may be effective for neuropsychiatric symptoms in COVID-19
Randomised controlled trials (RCTs) of interventions for neuropsychiatric complications of COVID-19 are still rare. This week, Liu and colleagues report a multi-centre RCT of computerised cognitive-behavioural therapy (cCBT) for depressive and anxiety symptoms in patients with mild COVID-19 (n=126), versus treatment as usual (n=126). Participants were recruited from five isolation hospitals in China and had mild-to-moderate depressive or anxiety symptoms as defined by the Hamilton Depression Rating Scale (HAM-D) score ≥7 and/or the Hamilton Anxiety Scale (HAM-A) score ≥7. The intervention consisted of several modules, including a cognitive therapy module aiming to minimize patients’ negative thoughts about COVID-19, stress- and sleep-management training, relaxation / mental imagery training, mindfulness meditation, and counting meditation. Participants engaged in self-directed therapy for at least 10 minutes per day, for one week. The primary outcome showed statistically and clinically significant reductions in both HAM-D and HAM-A scores, with the effect persisting at one month followup. Reasons for a cautious interpretation include the lack of blinding, short duration of follow-up, higher drop-out than expected at the follow-up point, and scant information about the COVID-19 clinical status of patients. The effect sizes are also striking for such a short intervention; the reasons for this are not clear. However it is good to see trials beginning to emerge which address how we might treat common neuropsychiatric symptoms arising in patients who have COVID-19, rather than simply assuming existing treatments will ‘map over’ effectively. Many of these symptoms are of a sort which might respond effectively to CBT – for example depression, anxiety, PTSD, insomnia, and fatigue – and the study by Liu et al. provides some early evidence in favour of non-pharmacological management strategies, in some patients at least.
Finer-grained evidence on vaccine-associated cerebral venous sinus thrombosis
Many readers of this blog will be familiar with the association between some SARS-CoV-2 vaccines and the very rare side effect of cerebral venous sinus thrombosis (CVST). To date, these have mostly been associated with the Oxford-AstraZeneca vaccine, which the US health authorities decided not to authorise. In their JAMA article, See et al. analyse CVSTs following the single-dose Johnson & Johnson (AKA Janssen) vaccine which were reported by clinicians to the US Vaccine Adverse Event Reporting System (VAERS), which is akin to the Yellow Card reporting system in the United Kingdom. This paper is timely, given the decision in the US to temporarily suspend the Janssen vaccine due to concerns about CVSTs. In total, they confirmed 12 cases of CVST which arose in the context of millions of vaccinations. All of their patients were relatively young White women. All of those tested (n =11) were positive for the heparin-platelet factor 4 HIT antibody, which in most cases was associated with significant drops in platelet count. Given the urgent nature of this publication, follow-up time was relatively short, but nevertheless four patients had returned home, and two had been stepped down from intensive care (ICU). Two remained in ICU, and two died. This paper adds further evidence that CVSTs are a real, but extraordinarily rare, complication of some SARS-CoV-2 vaccines. Policy makers should factor this into account when making decisions on ongoing vaccination efforts, whilst bearing in mind the high levels of neurological and neuropsychiatric complications seen in covid-19 illness itself (including, albeit less commonly, in younger people).
Neuropsychiatric symptoms are common and persistent in survivors of COVID-19.
Finally and rather shamelessly, we highlight the first systematic review and meta-analysis of the prevalence of neuropsychiatric symptoms in survivors of COVID-19, which went up on MedRxiv yesterday and which happens to be from our own team. Badenoch et al. carefully analysed 51 studies reporting the prevalence of sixteen neuropsychiatric symptoms in patients with post-acute, or “Long” Covid. The pooled analyses revealed insomnia, fatigue, anxiety, cognitive impairment, and post-traumatic stress symptoms to be the most commonly reported by survivors of COVID-19. We found surprisingly little evidence in the pooled data to suggest that these symptoms lessen in frequency as time passes after recovery from acute COVID-19: comparisons of studies reporting short-term (<12 week) outcomes revealed few if any differences with studies reporting outcomes at 12 weeks or later. Similarly there was little evidence of a relationship between symptoms and severity of the acute COVID-19 illness. The lack of a signal of recovery over time, or a clear relationship with acute severity, may be due to the relatively early stage of the literature, with relatively short follow-up durations and few generalisable community samples yet available. Our results are however the first data synthesis of neuropsychiatric symptoms in the post-acute phase. These symptoms are common among survivors of COVID-19 and relatively persistent at least during the first six months after recovery from infection. Treatments such as CBT may be helpful in some cases, and the data may be of interest to clinical service providers planning for ‘Long Covid”.
Other news in brief
Coming soon: the latest from MedRxiv
Case report roundup
New-onset psychosis due to COVID-19: A clinical case report of a man in his fifties with no psychiatric history, who was admitted to hospital with COVID-19 in November 2020 and spent 8 days in the ICU. Following his discharge, he was unable to sleep, was increasingly agitated, developed paranoid delusions and tactile and auditory hallucinations. His anxiety levels remained high. The patient was admitted to a psychiatric ward, since he developed haematomas as a result of hitting his head off the walls. He was treated with antipsychotic medication (risperidone 2mg, later increased to 4mg; and benzodiazepines), with most of his psychotic symptoms improving within 2 weeks. The patient was discharged home 3 weeks after the admission. He continued to take risperidone (4mg) and remained under the care of early intervention services (EIS), whilst benzodiazepines were discontinued.
Click on links of study types or syndromes above to go straight to the relevant papers in the database below
PUBLISHED RESEARCH DATABASE
The papers are separated into research papers and reviews, listed by topic in order of date of publication. Click on the titles to access the papers. We have added brief summaries of the papers and those judged to be of particular importance are denoted with an orange diamonds (♦).
If you would like to make any comments or suggestions, or alert us to new papers, please email email@example.com
Due to the large number of papers we have collapsed the list into subsections: please click on the relevant headings to view the papers.
1. DATA PAPERS
Publication date / reference: 23/04/2021 Meije et al. Long-term outcomes of patients following hospitalization for COVID-19: a prospective observational study. Clin Microbiol Infect.
Summary: The authors of this observational study analysed the follow-up data obtained from the survivors of hospitalisation for COVID-19. A total of 302 patients had a follow up appointment at an outpatient facility (45 days after discharge), whilst 294 patients were contacted by telephone (after a median time follow-up of 7 months). Patients were divided into 3 groups: PaO2/FiO2 > 300; PaO2/FiO2 300-200; PaO2/FiO2 < 200. The results of the outpatient follow-up assessment showed that 78% of patients had COVID-19-related symptoms. Including: asthenia (53%), respiratory symptoms (56%) and residual pulmonary radiographic lesions (40%). PaO2/FiO2 < 200 was an independent predictor of persistent dyspnea, whilst PaO2/FiO2 > 300 correlated with resolution of chest radiographic lesions. Specific medical follow up was required by 50% of patients after the first consultation. The results from the telephone follow-up showed that 50% of patients presented COVID-19-related symptoms and 49% of patients were suffering from psychological disorders. 27% of patients had asthenia and 10% presented with dyspnea, independently of PaO2/FiO2 ratio. This study highlights the importance of long-term follow-up of COVID-19 patients, with particular attention to be drawn to patients with low PaO2/FiO2 ratio during acute illness.
Publication date / reference: 27/04/2021 Fan et al. Neurological diseases and risk of mortality in patients with COVID-19 and SARS: a territory-wide study in Hong Kong. J Neurol Neurosurg Psychiatry.
Summary: A territory-wide retrospective cohort study was performed using data from electronic database in Hong Kong (Clinical Data Analysis and Reporting System) that contains information about patients’ demographic, diagnoses, procedures and treatment, laboratory results and death. CDARS represents in-patient data of 80% – 90% of the 7.49 million population in Hong Kong.
The results showed that the three main predictors of mortality from COVID-19 are: advanced age, renal diseases and stroke. SARS mortality was also investigated, with the results demonstrating that advanced age and Parkinson’s Disease (PD) are the two outstanding predictors of mortality. Both SARS-CoV and SARS-CoV-2 induced significant inflammatory and immune responses, with worse outcomes noted in patients with neuroinflammation and chronic neurological conditions. The diagnosis and management of COVID-19 infected patients with neurological disabilities (especially those of advanced age) was delayed due to their inability to express their discomfort, thus leading to increased mortality.
The study concluded that patients with underlying neurological conditions, particularly PD and stroke, should be prioritised for vaccination to reduce the morbidity and mortality from both COVID-19 and SARS infections.
Publication date / reference: 27/04/2021 Dobre et al. Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study. Psychol Med.
Summary: This study aimed to assess clinical features and outcomes of 350 COVID-19 patients with previous psychiatric conditions across 22 wards, and measured the number of patients who were transferred to somatic care units, developed an acute confusional state and who died. The study found 7% of the patients were transferred to somatic care units which was predicted by severe respiratory symptoms. 15% developed acute confusion, which was negatively associated with smoking. 2% died, and in univariate analysis, mortality was predicted by age, an organic mental disorder, acute confusion, and severe respiratory symptoms. The authors highlighted a need for caution when treating COVID-19 patients with severe psychiatric disorders given their multiple somatic comorbidities and risk of confusion.
Publication date / reference: 03/05/2021 Bulbuloglu S, Altun Y., The effect of sniffing Turkish coffee on olfactory disorders in COVID-19 patients: An experimental clinical study
Summary: This study examined the effect of sniffing Turkish coffee on the COVID-19 patients’ sense of smell. A patient and disease information form was used to collect data, alongside the Connecticut Chemosensory Clinical Research Center (CCCRC) Test. The results have shown that 58.3% of patients had severe hyposmia; 25% of patients had moderate hyposmia and 16.7% of patients had anosmia prior to sniffing Turkish coffee. Following patients’ exposure to the smell of Turkish coffee, 13.3% of patients regained their ability to smell and 18.3% of patients had mild hyposmia. Further 45% of patients had moderate hyposmia; 6.7% had severe hyposmia; and 16.7% of patients had anosmia. No difference was observed in the control group between the two measurements. This study has indicated that COVID-19 patients regained some of their normal sense of smell for one hour, following sniffing Turkish coffee. Since Turkish coffee is fragrant, affordable and widely accessible, it could potentially be recommended for treatment of olfactory disorder in COVID-19 patients.
Publication date / reference: 29/04/2021. Eric Kelleher et al. Consultant psychiatrists’s experience of the impact of the COVID19 pandemic on mental health services in Ireland. Ir J Psychol Med
Summary: This study aimed to record experiences of Consultant Psychiatrists during lockdown, as well as their impression on the impact of lockdown on Mental Health Services. Data was collected through A questionnaire designed by the Royal College of Psychiatrists, and circulated to consultant members. This questionnaire assessed the impact of COVID19 in several areas: (1) delivery of clinical services (2) mental health act (MHA) provision (3) working day of Consultant Psychiatrists (4) availability of Information Technology (IT) equipment (5) well-being of consultants and (6) Personal Protective Equipment (PPE). The response rate was 32% (N=197/623), however not all respondents answered all questions. Overall, most consultants reported decreased referrals in the first month and an increase in the second month. Consultants also reported that their working day was affected, and IT equipment was inadequate. Overall, this study supports the need to increase funding in mental health services in Ireland.
Publication date / reference: 20/04/2021 Cao et al. Three-month outcomes of recovered COVID-19 patients: prospective observational study. Ther Adv Respir Dis.
Summary: In this prospective observational study with 81 participants with COVID-1, the authors followed up 62 individuals at 1 month and 61 at 3 months and found that at 3 months, chest CT abnormalities were present in one half of COVID-19 survivors and worse chest CT scores were independently associated with older age and steroid administration during hospitalization. Residual pulmonary function impairments were modest, whereas exercise capacity and SF-36 social functioning scores were significantly lower than the general population.
Publication date / reference: 08/04/21. Zifko et al. Covid-19: Involvement of the nervous system. Identifying neurological predictors defining the course of the disease. J Neurol Sci.
Summary: In a retrospective case-note review of 40 inpatients and 42 outpatients with Covid-19, the authors found high rates of fatigue, headache, loss of taste, and loss of smell. Dementia, hallucinations, and confusion indicated a poor prognosis.
Publication date / reference: 08/04/2021 Mahmud et al. Post-COVID-19 syndrome among symptomatic COVID-19 patients: A prospective cohort study in a tertiary care centre of Bangladesh. PLoS One.
Summary: This prospective cohort study was conducted to determine the prevalence and risk factors for post-COVID-19 syndrome amongst patients hospitalised for COVID-19 in Bangladesh (n=355). Of the patients followed up in this study, 46% developed post-COVID-19 symptoms including fatigue which was found in 70% of those with the syndrome. Factors that increased the risk of developing this syndrome included female sex (RR 1.2, 95% CI 1.0-1.19), respiratory distress (RR: 1.3, 95% CI: 1.4-1.56) and long duration of disease (RR: 1.09, 95% CI: 1.00-1.19).
Publication date / reference: 08/04/2021 Flores-Silva et al. Neurologic manifestations in hospitalized patients with COVID-19 in Mexico City. PLoS One.
Summary: The authors of this retrospective cohort study aimed to identify predictors of neurological symptoms in COVID-19 disease amongst hospital patients (n=1072). Standardised, structured interviews and physical examinations were used alongside laboratory testing to confirm neurological manifestations amongst the cohort. The predictors of neurological symptoms were found to be pre-existing neurological disease, age, headache at presentation and invasive ventilation.
Publication date / reference: 01/04/2021 Taquet et al. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry.
Summary: As well as the enormous sample size of this paper (more 80 million subjects with 236,379 COVID-19 survivors), what is particularly helpful is a comparison to influenza. Worryingly, in the six months following a COVID-19 diagnosis, about a third of survivors had a neurological or psychiatric disorder and hazard ratios were substantially higher than in influenza for most outcomes. The study replicates earlier findings of an increased risk of stroke (interestingly both ischaemic and haemorrhagic) as well as the more novel and concerning finding of an increased risk of incident dementia. Interestingly, the highest hazard ratio compared to influenza is for myoneural junction and muscle disease, but the specific nature and aetiology of this remains rather unclear.
Summary: The authors of this prospective cohort study aimed to identify the effect of SARS-CoV-2 on cranial nerves (n=356). 135 patients demonstrated cranial nerve involvement, with the facial nerve (30.8%) and olfactory (27.2%) being the most commonly affected. There were no statistically significant demographic differences between those who had cranial nerve involvement compared to those who did not. However, those with cranial nerve involvement had significantly more symptoms of sore throat (p<0.001), tiredness (p=0.005) and headache (p=0.008). This study has demonstrated that cranial nerve involvement in COVID-19 is extensive and involves more than simply taste and smell disturbances.
Publication date / reference:. Apr 2021. Yuksel et al. Neurological manifestations of COVID-19 in confirmed and probable cases: A descriptive study from a large tertiary care center. J Clin Neurosci.
Summary: The authors aimed to identify the most common neurological symptoms and findings of COVID-19 in hospitalized patients, investigate the relationship between these symptoms and clinical, radiological, and laboratory findings, and assess the impact of neurological manifestations on mortality. They studied 307 patients referred for neurology consultation. In this selected sample the authors reported that “the most prominent neurological manifestation in both confirmed and probable cases was altered mental status. Infarct was the most common neuroimaging finding. The mortality rate for confirmed and probable cases was similar. In the case of mental deterioration, the mortality rate was found to increase dramatically. Brain edema, hemorrhage, neurological comorbidity, the severity of lung involvement, and age were independent risk factors for mental deterioration.”
Publication date / reference: 10/3/2021 Sánchez-Morales et al. Neurological manifestations temporally associated with SARS-CoV-2 infection in pediatric patients in Mexico. Childs Nerv Syst.
Summary: This study aimed to describe the temporal association of specific acute neurological symptoms in (n=23) pediatric patients with (n=10) confirmed SARS-CoV-2 infection. The authors found that 50% were males aged 2-16 years old. 40% confirmed a close contact with a relative positive for SARS-CoV-2, while 60% had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. They concluded that neurological manifestations temporally associated with SARS-CoV-2 infection in the pediatric population even without respiratory symptoms. SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.
Publication date / reference: 17/03/2021 Salari et al. Seroprevalence of SARS-CoV-2 in Parkinson’s Disease Patients: A Case-Control Study. Mov Disord.
Summary: In this case-control study 90 patients with Parkinson’s disease and 97 controls from the Shohada‐e‐Tajrish University Hospital in Iran, all without symptoms for COVID-19 were tested for IgG antibodies for SARS-CoV-2 IgG. About 25.56% of patients with PD and 12.37% of controls tested positive for SARS-CoV-2 IgG antibody (p<0.05). There was no statistically significant difference in IgG ratio in PD patients and controls, who did not have a direct contact with SARS-CoV-2 positive individuals, however the authors stated that such existed between PD patients and controls with indirect contact. The mean total IgG ratio was 1.53 ± 3.36 for the PD group and and 0.80 ± 2.17 for the control group (p<0.01).
Publication date / reference: 04/03/2021 Abdalkader et al. Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. J Stroke Cerebrovasc Dis.
Summary: This multi-centre, retrospective, cross-sectional study aimed to review the clinical and radiological characteristics of cerebral venous sinus thrombosis associated with COVID-19. They identified seven patients for inclusion. 7/8 were female. They presented with non-specific symptoms such as headache, fever, gastrointestinal upset. 2/8 had focal neurology and 2/8 had impaired consciousness. 6/8 involved the superior sagittal or transverse sinus. 1/8 patients died.
Publication date / reference: 20/03/2021 Sun et al. Symptomatic features and prognosis of 932 hospitalized COVID-19 patients in Wuhan. J Dig Dis.
Summary: This retrospective cohort study aimed to explore detailed symptomatic features of COVID-19. The authors enrolled (n=932) hospitalized patients with COVID-19 in Wuhan, including 52 severe cases and 880 non-severe cases, and analyzed the symptomatic features. The most common symptoms were fever (60%), cough (50.8%), and fatigue (36.4%), followed by anorexia (21.8%) and dyspnea (19.2%). The median duration of fever was 7 days, which was characterized by persistent low fever. The median duration of cough was 17 days, characterized by dry cough without sputum. Most dyspnea occurred on the fourth day after illness onset, with a median duration of 16 days. The incidences of taste loss and olfactory disturbance were only 6.2% and 3.1%, respectively. After adjusting age and gender, multivariate regression analysis showed that fever lasting for more than 5 days, anorexia at onset, and modified Medical Research Council level above grade 2 when dyspnea occurred were symptomatic risk factors for severe COVID-19. Through follow-up, cough (6.2%), dyspnea (7.2%), fatigue (1.8%), olfactory and taste disorders (1.5%) were the significant remaining symptoms. They concluded that COVID-19 caused clusters of symptoms with multiple systems involved. Certain symptomatic characteristics have predictive value for severe COVID-19. Short-term follow-up showed that most patients had a good prognosis.
Publication date / reference: 01/03/2021. Boddington et al. Epidemiological and clinical characteristics of early COVID-19 cases, United Kingdom of Great Britain and Northern Ireland. Bull World Health Organ.
Summary: As part of the World Health Organisation (WHO) first few X enhanced surveillance protocol, this paper reports epidemiological and clinical characteristics of COVID-19 cases in the UK between 31 Jan 2020 – 9th April 2020 (N=381). From a neuropsychiatric point of view, the study reported that fatigue and muscle ache was one of the most frequent symptoms reported (70.9% & 50.9%). And almost half of those cases reported anosmia during their illness (48.5%). An additional interesting finding is that almost half of the cases were imported, with the majority having recent travel history from Italy (51.4%).
Publication date / reference: 26/02/21 Fleischer et al. Observational cohort study of neurological involvement among patients with SARS-CoV-2 infection. Ther Adv Neurol Disord
Summary: This is a prospective cross-sectional study which evaluated the phenomenology and potential pathophysiology of neurological manifestations in 102 PCR-confirmed COVID-19 patients. It was determined that 59.8% of patients had neurological manifestations. Of which, 24.5% were non-specific presentations including general weakness, cognitive decline or delirium. Unsurprisingly, mild derangement was commonly seen (mostly altered smell/ taste – 9.8%). Whereas severe neurological findings were detected in 23.5% – half of which included cerebral ischaemia. Concordant with other epidemiological reports, severe COVID-19 disease was more associated with neurological manifestations.
Publication date / reference: 12/3/21 He et al. neurological and psychiatric presentations associated with COVID-19. Eur Arch Psychiatry Clin Neurosci.
Summary: He et al aimed to identify the prevalence and biochemical correlates of neuropsychiatric presentations of COVID-19 (n=77). 50.6% (n=39) of patients admitted to hospital with COVID-19 during the study period presented with psychiatric symptoms; the most common of which was insomnia. Those with neurological presentations had significantly higher blood urea nitrogen, cystatin C and CRP levels. The authors suggest the findings may reflect a pro-inflammatory reaction to COVID-19 in the CNS thus accounting for these presentations.
Publication date / reference: 04/03/2021 Harrison et al., Associations between COVID-19 and 30-day thromboembolic events and mortality in people with dementia receiving antipsychotic medications. Pharmacol Res.
Summary: This retrospective cohort study aimed to characterise individuals with COVID-19 and dementia, and the use of antipsychotics in this population during the pandemic. The control group were historical controls from 2019. The main findings were presentations to healthcare decreased in the COVID-19 group compared to 2019, but the proportion receiving antipsychotics were higher in the COVID-19 2020 group compared to the 2019 controls.
Publication date / reference: 19/02/21. Dhillon et al. Neurological Disorders Associated With COVID-19 Hospital Admissions: Experience of a Single Tertiary Healthcare Center. Front Neurol.
Summary: In this study, 29 patients with identified neurological disorders associated with confirmed or probable SARS-CoV-2 infection were identified and included. With a mean age of 68.9 ± 13.5 (SD) and a 16:13 male:female ratio, eight patients required critical care admission, six of whom were mechanically ventilated. At presentation, symptoms included reduced consciousness, confusion, seizures, acute neurological deficits and the acute onset of movement disorders. 16 had a cerebrovascular event, seven had inflammatory, non-inflammatory and autoimmune encephalopathy, three had movement disorders and three experienced peripheral nervous system syndromes. Interestingly, of the peripheral nervous system disorders, one was diagnosed as Guillain-Barré syndrome, one with an atypical acute inflammatory demyelinating polyneuropathy and one with brachial plexopathy with bilateral hearing loss. The authors hereby presented a wide variety of neurological sequelae associated with COVID-19 and discussed potential mechanisms for the neurotropic effects of SARS-CoV-2.
Publication date / reference: 05/03/2021 Chachkhiani et al. Neurological Complications of COVID19 during March 2020 at LCMC Health University Medical Center: Dataset. Data Brief.
Summary: This is the published data set and proposal outline for a previously documented article by the same authors. The authors hope this will allow for larger data sets for neurological complications to be built to allow for meta-analysis.
Publication date / reference: 12/03/2021 Ermis et al. Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients. Neurol Res Pract.
Summary: This cross-sectional monocentric study aimed to investigate the spectrum of COVID-19 symptoms. The authors described the neurological manifestations and complications of (n=53) patients with SARS-CoV-2 infection who have been hospitalized between March and September 2020 at the RWTH University Hospital Aachen, Germany. They found coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. They obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. They concluded that results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.
Publication date / reference: 29/01/21. Le et al. Multinational Prevalence of Neurological Phenotypes in Patients Hospitalized with COVID-19. MedRxiv (not peer-reviewed)
Summary: This is a retrospective observational study of electronic health record data from 348 hospitals across 6 countries, which evaluated the frequency of ICD-19 coded neurological complications in patients admitted with COVID-19 (n=35,177). Neurological complications were included if they were not coded at admission but coded during hospital stay. The most common complications were disorders of consciousness (5.8%) and unspecified disorders of the brain (8.1%). Subgroup analysis of disease severity found that patients with more severe COVID-19 disease had a greatly increased risk of developing a neurological complication above those with less severe disease (e.g., altered consciousness relative risk increase of 22%; 37% increase in encephalitis and/or myelitis and 72%).
Publication date / reference: 01/03/2021. Sandoval et al. Neurologic Features Associated With SARS-CoV-2 Infection in Children: A Case Series Report. J Child Neurol.
Summary: In this single centered retrospective case series report, authors aimed to look at neurological manifestation of COVID-19 in children (age<18) (N=90). They reported 13 cases (14.4%) patients admitted with confirmed covid-19 had neurological symptoms. The symptoms were of a wide range: headache, muscle weakness, anosmia, ageusia, status epilepticus, Guillain-Barré syndrome, encephalopathy, demyelinating events. Due to the limitation in study design, the authors were unable to establish direct causality of neurological symptoms and COVID-19. It is worth noting that in the majority of the cases the neurological symptoms resolved as systemic presentation subsided.
Publication date / reference: 25/02/2021 Khedr et al. Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals. Neuroepidemiology.
Summary: This two-centre retrospective study evaluated neurological symptoms in COVID-19 inpatients (n=439). Neurological symptoms were identified in 222 patients and in 117 these were acute. Neurological complications identified were both pertaining to CNS and PNS. The most common was stroke (55;12.5%) and the majority of these were ischaemic in nature (42;9.6%). Other CNS complications included: encephalitis, seizures and MS relapses. In addition, the authors note PNS complications – 31 patients had anosmia and ageusia, 4 patients had GBS.
Publication date / reference: 23/02/2021 Travi et al. Neurological manifestations in patients hospitalized with COVID-19: a retrospective analysis from a large cohort in Northern Italy. Eur J Neurosci.
Summary: This single centre retrospective cohort study assessed 901 patients admitted to a single hospital with COVID-19. They found that 42.6% showed severe or critical disease with a mortality of 21.2%. At least one neurological symptom was observed in 30.2%. Patients who had respiratory symptoms had a higher mortality compared to those with purely neurological symptoms and confounding for risk factors and demographics, isolated neurological symptoms displayed a better survival. Individuals with stroke had the worst mortality.
Publication date / reference: 22/02/2021 García-Azorín et al. Neurological symptoms in Covid-19 patients in the emergency department. Brain Behav.
Summary: Retrospective case notes review of 576 hospitalised covid-19 patients. Neurological manifestations were common upon presentation to the emergency department;anosmia (25%), myalgia (24%), headache (23%), and altered mental status (17%). Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.
Publication date / reference: 19/2/21 Bitan et al. COVID-19 prevalence and mortality among schizophrenia patients: A large-scale retrospective cohort study. Schizophr Bull.
Summary: This retrospective study aimed to identify the morbidity and mortality of COVID-19 amongst 51,078 schizophrenia patients living in Israel. The patients were age and sex matched with controls in order to calculate the odds ratio’s associated with schizophrenia diagnosis; sociodemographic variables were controlled for. The authors found that patients with schizophrenia were 2.15 times more likely to be hospitalised with COVID-19 (95% CI 1.63-2.82, p<.0001). This group were 3.27 times more likely to die from COVID-19 when compared with controls (95% CI 1.39-7.68, p<.0001). Rates of comorbidities such as diabetes (OR 1.65), COPD (OR 2.32) and obesity (OR 1.68) were significantly higher in the schizophrenia group (p<.0001).
Publication date / reference: 15/02/2021. G O’Sullivan et al. Covid-19 presentation among symptomatic healthcare workers in Ireland. Occup Med (Lond).
Summary: This was a case-control study of healthcare workers (n = 306) who presented for a covid-19 swab due to possible symptoms. Of the 102 with covid-19, 35% had headache, 23% fatigue, 29% myalgia, and 4% had anosmia as part of their illness.
Publication date / reference: 13/02/21 Dravid et al. Neurological issues during severe COVID-19 in a tertiary level hospital in Western India. Neurosci Lett.
Summary: Encephalopathy (5.2 %) and new onset large vessel ischemic stroke (1.1%) were the most common secondary neurologic complications noted in this retrospective case note review study of 423 patients with severe COVID-19. The authors claim “the first report of the spectrum of neurological disorders observed in patients with severe COVID-19 from a resource limited setting like India”.
Publication date / reference: 11/02/2021 de Langavant et al. Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series. Rev Neurol (Paris).
Summary: This was a small (n = 26) single-site retrospective study of hospitalised patients with neurological syndromes associated with COVID-19 in the first-wave in France. The authors noted a spread of syndromes including encephalitis (n = 8), encephalopathy (n = 6), strokes (6), and GBS (n = 2). CSF was negative for SARS-CoV-2 in all cases. Cases of encephalitis had evidence of CSF inflammation, however MRI brain imaging was normal in all eight, and EEG only showed (non-specific) changes in two.
Publication date / reference: 09/02/2021. Sun et al. A Clinical Analysis of Extrapulmonary Complications in Novel Coronavirus Pneumonia Patients. Int J Gen Med.
Summary: Retrospective study aims to investigate presence of extrapulmonary complications in confirmed COVID-19 pneumonia patients (N=500). 152 (without prior chronic disease) were found to have extrapulmonary syndrome. Of specific note 25 of those had nervous system damage (16/45%).
Publication date / reference: 29/01/2021 Le et al. Multinational Prevalence of Neurological Phenotypes in Patients Hospitalized with COVID-19. MedRxiv preprint.
Summary: This multi-national cross-sectional study of 35,177 hospitalized patients with SARS-CoV-2 infection found there was increased prevalence of disorders of consciousness and unspecified disorders of the brain, compared to pre-admission prevalence. Furthermore, during admission patients with severe COVID-19 had increased relative risk of consciousness disorders (22%), cerebrovascular disease (24%), non-traumatic intracranial haemorrhage (34%), encephalitis / myelitis (37%) and myopathy (72%).
Publication date / reference: 09/02/2021 Chuang et al. Neurological manifestations as primary presentation of COVID-19 in hospitalized patients. Acta Neurol Scand.
Summary: This retrospective study aimed to characterize patients with COVID-19 who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. The author identified COVID-19 patients ≥18 years that had neurology symptoms on presentation requiring neurology consultation between March 2020 and May 2020 and found 56 out of 282 patients who had neurology consult during this period, tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients had no typical COVID-19 symptoms (10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. They concluded that patients who have COVID-19 can present with serious neurologic symptoms even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.
Publication date / reference: 11/02/2021. Del Brutto et al. Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection. A longitudinal prospective study nested to a population cohort. Eur J Neurol.
Summary: In this cross-sectional study, Del Brutto and colleagues aimed to identify the frequency with which cognitive decline occurs in a cohort of individuals with a history of mild symptomatic SARS-Cov-2 infection (n = 93) who had had received a cognitive assessment prior to contracting SARS-Cov-2 and had normal MRI and EEG recordings. Individuals who required oxygen therapy or hospitalisation and those with a history of stroke or seizures were excluded. Cognitive decline was recognised in 11/52 seropositive and 1/41 seronegative individuals. Multivariate analyses showed that the odds for developing cognitive decline was 18.1 times higher among SARS-Cov-2 seropositive individuals.
Publication date / reference: 04/02/2021 Mendes et al. Delirium in older patients with COVID-19: prevalence, risk factors and clinical relevance. J Gerontol A Biol Sci Med Sci.
Summary: This retrospective cohort study assessed 235 patients who were over 65 years old with COVID-19. They found 20.4% of patients presented with delirium, of which 41.6% were hypoactive. Those with established cognitive impairment were at higher risk of developing this. The presence of delirium did not affect the length of stay in hospital but did worsen mortality.
Publication date/reference: 03/02/2021 Mendez et al., Short-term Neuropsychiatric Outcomes and Quality of Life in COVID-19 Survivors. J Intern Med.
Summary: This was a cross-sectional prospective analysis of hospitalised COVID-19 patients (n=179) who were followed-up for 2 months after discharge. Primary outcomes were neurocognitive function, psychiatric symptoms, and quality of life (QoL). A considerable prevalence of all three (neurocognitive function, psychiatric symptoms, and quality of life) were observed in the acute 2-month phase, however it is unclear if the impacts persist in the long-term.
Publication date / reference: 27/01/21. Nemani et al. Association of Psychiatric Disorders With Mortality Among Patients With COVID-19. JAMA Psychiatry.
Summary: The authors of this retrospective cohort study aimed to assess whether a diagnosis of a schizophrenia spectrum disorder, mood disorder, or anxiety disorder is associated with mortality in patients with COVID-19. Based on review of their clinical notes the authors categorised n=7348 consecutive adult patients as having ICD10-CM (1) schizophrenia spectrum disorders, (2) mood disorders, (3) anxiety disorders, or 4) no such disorders. Subjects were followed for 45 days from their positive SARS-CoV-2 PCR. The authors found that a premorbid diagnosis of a schizophrenia-spectrum disorder (n=75) significantly predicted mortality after adjusting for clinico-demographic risk factors (odds ratio [OR], 2.67; 95% CI, 1.48-4.80). A premorbid diagnosis of mood disorders (OR, 1.14; 95% CI, 0.87-1.49) or anxiety disorders (OR, 0.96; 95% CI, 0.65-1.41) did not independently predict mortality. Strikingly, having schizophrenia ranked behind only age in strength of an association with mortality. The sample was over-represented for symptomatic and high-risk people able to access testing during the peak of the pandemic in New York City. Possible mechanisms underlying the association were not studied. Unmeasured medical comorbidities or/and delays in treatment seeking may have contributed to worse outcomes, and the relatively small number of patients with schizophrenia-spectrum disorders indicates caution. However the authors claim their analysis as the first US study to report the risk of COVID-19 mortality by psychiatric diagnostic group.
Publication date / reference: 04/02/21. Hoertel et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry.
Summary: Writing in Molecular Psychiatry, Hoertel et al. noted recent publications implicating antidepressant use with resolution of systemic inflammatory markers, and proposed the hypothesis that antidepressants may therefore be potentially useful in reducing the risk of intubation or death in patients with COVID-19. Using a retrospective cohort design they examined data on 7230 adult patients with confirmed COVID-19 who had been consecutively admitted to 39 Greater Paris University hospitals. Antidepressant use was defined as receiving any antidepressant within the first 48 h of hospital admission, and the primary endpoint was the time from study baseline to intubation or death. A total of 345 patients (4.8%) received an antidepressant within their timeframes. The authors reported that their primary multivariable analyses with “inverse probability weighting” showed a significant association between use of any antidepressant and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43–0.73, p < 0.001). The simple raw proportions of outcomes on or off antidepressants did not suggest such a protective effect – it was seen only after preparing the raw data by means of complicated statistical weighting which this reviewer is unable to appraise, though the results were seemingly robust to multiple sensitivity analyses. The authors speculate on several potential mechanisms for their observation, including inhibition of acid sphingomyelinase activity; S1R agonism; IL-6, IL-10, TNF-α, or CCL-2 attenuation; or direct antiviral effects. They call for double-blind RCTs of antidepressants in COVID-19 patients.
Publication date / reference: 19/12/20. Pimlott et al. Clinical learnings from a virtual primary care program monitoring mild to moderate COVID-19 patients at home. Fam Pract.
Summary: The authors of this retrospective study of 98 community-dwelling COVID-19 patients found symptoms of fatigue in 60.3%, headache in 42.5% and myalgia in 39.7%.
Publication date / reference: 18/12/21. Eskander et al. Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19. Neurology.
Summary: In this study, 581 patients with neurological manifestations of COVID-19 and available neuroimaging with 1743 matched controls with covid-19 not featuring neurological manifestations. Controlling for age and disease severity, delirium (OR 1.4) and stroke (OR 3.1) were associated with death.
Publication date / reference: 15/12/2021. Zhao et al. A disease progression prediction model and nervous system symptoms in coronavirus disease 2019 patients. Am J Transl Res.
Summary: In this retrospective study of 417 hospitalised covid-19 patients, the presence of any neurological symptom was associated with more severe COVID-19 (OR 3.5) in a binary severe/non-severe log regression model.
Publication date / reference: 21/12/2020. Wang et al. Retrospective study of clinical features of COVID-19 in inpatients and their association with disease severity. Med Sci Monit.
Summary: This retrospective single-centre study aimed to investigate the clinical and test features of COVID-19 inpatients (n=61) and how this linked to disease severity. The authors divided the patients into groups depending on severity. The authors found that respiratory indicators such as dyspnoea, linked to greater disease severity. Of the total, 15 (24.6%) had myalgia, 12 (19.7%) had dizziness and 33 (54.1%) had fatigue.In particular, in the severe group (n=24), patients had increased LDH, CRP, creatinine and prolonged PT. The findings suggest that higher severity may be associated with elevated CRP, prolonged PT and a higher MPVLR.
Publication date / reference: 21/01/2021. Portela-Sanchez et al. Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic. Eur J Neurol.
Summary: In this single centered prospective cohort study, authors sought to describe neurological diagnoses that arose after the onset of COVID-19 symptoms in hospitalised patients over a 3 months period (N=2750). They reported that only 2.6% (N=71) hospitalised patients were found to have at least one neurological complications (out of a total of seventy seven possible ones). Among these 71 patients the most common complications were neuromuscular disorders, cerebrovascular disorders, and delirium. The findings indicated a low overall incident neurological complications associated with SARS-CoV2. Moreover, the heterogeneity of the clinical manifestations points to different causal mechanisms and the authors commented that within their study cohort, there was no evidence to suggest a potential direct invasion of the nervous system by SARS-CoV2.
Publication date / reference: 21/12/20. Brucki et al. Neurological complications in COVID-19 patients from Latin America. Brain
Summary: The authors of this retrospective cohort study evaluated 1201 patients admitted to hospital with COVID-19 and who underwent neurological consultation between 1st March – 30th April 2020. There was evidence of neurological complications in 5.24% (63/1201) patients. Of these patients, 43 had confirmed COVID-19 whereas the remainder had probable disease. Seventeen (27%) had pre-existing neurological disease (most commonly myasthenia gravis) but the majority (73%) had new onset nervous system manifestations. Similar to other epidemiological studies, the most frequent manifestations were stroke (30/63, 25 ischaemic and 5 haemorrhagic), encephalopathy (n=17) and seizures (n=5).
Publication date / reference: 17/12/2020. Elimian et al. Patient characteristics associated with COVID-19 positivity and fatality in Nigeria: retrospective cohort study. BMJ Open.
Summary: This is a retrospective cohort study of confirmed cases of COVID-19 in Nigeria (n = 10517). The authors report that loss of smell (aOR 7.78, 95% CI 5.19 to 11.66) and loss of taste (aOR 2.50, 95% CI 1.60 to 3.90) were independently associated with COVID-19 infection. The authors note that these findings are similar to other international studies.
Publication date / reference: 01/01/2021 Qu et al. A quantitative exploration of symptoms in COVID-19 patients: an observational cohort study. Int J Med Sci.
Summary: This was an ambispective observational cohort study (n=133), analysing characteristics and changes of symptoms in confirmed COVID-19 patients. The core symptoms found in all types related to upper respiratory tract infection, cardiopulmonary function, and digestive system. Dyspnoea was correlated with critical type, and dyspnoea (P<0.001), shortness of breath (P<0.01) and chest distress (P<0.05) were correlated with death with their corresponding coefficient being 0.393, 0.258, 0.214, respectively.
Publication date / reference: 9/12/20 Alonso et al. Mental Health Impact of the First Wave of COVID-19 Pandemic on Spanish Healthcare Workers: a Large Cross-sectional Survey. Rev Psiquiatr Salud Ment.
Summary: This multicentre, cross-sectional cohort study assessed the mental health, SARS-CoV-2 exposure and demographics of 9138 health care workers. They found prevalence of mental health disorders, worse among certain demographics including: female, not from Spain, and particularly nurses and auxiliary nurses. Those with higher SARS-CoV-2 exposure and hospitalised with COVID-19 had a greater risk of mental health difficulties.
Publication date / reference: 5/12/20 Daly et al. Associations between periods of COVID-19 quarantine and mental health in Canada. Psychiatry Res.
Summary: This cross sectional cohort study assessed 3000 individuals in Canada who had undergone quarantine to see the effect it had had on their mental health. It showed that there was a higher odds ratio for suicidal ideation and deliberate self harm; however, the reason for the isolation did change these odds ratio with no increase if the reason was due to quarantine after travel.
Publication date / reference: 12/2020 Chen et al. Epidemiological analysis of 18 patients with COVID-19. Eur Rev Med Pharmacol Sci.
Summary: Description of eighteen patients with covid-19. In total, 7/18 had fatigue, 3/18 had headache and dizziness, and 2/18 myalgia.
Publication date / reference: 27/11/2020 Battaglini et al. Neurological Complications and Noninvasive Multimodal Neuromonitoring in Critically Ill Mechanically Ventilated COVID-19 Patients. Front Neurol
Summary: In this retrospective observational study on 94 patients with COVID-19, admitted to ICU, Battaglini et al. demonstrated that around 50% of severely ill patients experienced neurological complications (47 out of 94 patients), the most common being delirium (34 patients, 36.17%). Other neurological complications were much less common with incidence around and less than 5 % (5 patients (5.32%) experienced critical illness neuropathy; 4 patients (4.25%) fell into coma and etc.). Mechanical ventilation was strongly associated with the development of neurological complications; however neurological complications were not associated with higher mortality rates, but could be associated with longer hospital stay. The authors also suggested that noninvasive neuromonitoring modalities could be useful for early detection of patients at risk of longer stay at ICU, as increased intracranial pressure, measured by optic nerve sheath diameter (ONSD) proved to be significantly associated with this outcome.
Publication date / reference: 24/11/20. Kushwaha et al. Neurological Associations of COVID-19-Do We Know Enough: A Tertiary Care Hospital Based Study. Front Neurol.
Summary: This study discusses 14 laboratory confirmed SARS-CoV-2 positive patients presenting with neurological signs and symptoms.
Publication date / reference: 11/12/2020. Jacobs et al. Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One.
Summary: This prospective cohort study aimed to characterise the prevalence and persistence of COVID-19 symptoms following hospital admission, in order to help with planning provision of community clinical services. N=183 patients reported persistence of their symptoms at 35 days. The authors concluded that the persistence of COVID-19 symptoms has a significant impact on several factors such as quality of life, mental health, and physical function. The authors suggested early post-acute evaluation of symptoms in order to better plan provision of community clinical services.
Publication date / reference: 04/12/2020 Mizrahi et al. Longitudinal symptom dynamics of COVID-19 infection. Nat Commun.
Summary: Mizrahi and colleagues present their findings of longitudinal dynamics of symptoms prior to and throughout SARS-CoV-2 infection, obtained through primary care electronic health records (EHR) and nationwide surveys from March-June 2020. The authors found that the data obtained from EHR and surveys were discordant – with surveys being more sensitive in capturing symptoms (likely due to higher self reporting). Among 2471 individuals with COVID-19, the most common symptoms were fever, cough and fatigue. Loss of smell and taste was the most predictive for a positive result – even up to 3 weeks prior to diagnosis. Children seemed to have a shorter clinical course of symptoms. Survey data from 278 patients also revealed persistent fatigue, myalgia, runny nose and shortness of breath for weeks after recovery.
Publication date / reference: 1/12/2020 Mirfazeli et al. Neuropsychiatric manifestations of COVID-19 can be clustered in three distinct symptom categories. Sci Rep.
Summary: This single centre Iranian paper reviewed 201 patients with COVID-19 to assess and categorise symptomology. They found that 151 patients displayed at least one neuropsychiatric symptom; the most common being: limb force reductions; headache, anosmia, and hypogeusia. They found through hierarchical clustering that neuropsychiatric symptoms group together in three distinct presentations: anosmia and hypogeusia; dizziness, headache, and limb force reduction; photophobia, mental state change, hallucination, vision and speech problem, seizure, stroke, and balance disturbance.
Publication date / reference: 14/08/2020. Garg et al. Neurological Symptoms as Initial Manifestation of Covid-19 – An Observational Study. Ann Indian Acad Neurol.
Summary: This prospective study from India recruited 391 patients admitted to hospital with covid-19. Information was collected via a questionnaire, though it does not state at what point following a positive SARS-CoV-2 test this was conducted. New-onset neurological symptoms were found in 106 (27.1%). Of these, dysguesia (33.1%), anosmia (24.5%), and headache (22.6%) were the most common. In total, 38 (9.7%) reported similar neurological symptoms as the initial manifestation of their acute covid-19 illness.
Publication date / reference: 12/11/2020 Kong et al. Clinical characteristics of the first known cases of death caused by COVID-19 pneumonia. Aging (Albany NY).
Summary: This case series looked at the characteristics of the first 17 deaths from COVID-19 in Wuhan. They found that they were predominantly older males who presented with fever, fatigue, respiratory symptoms and neurological symptoms. The majority died secondary to ARDS and they state that advanced age and male gender predict severity.
Publication date / reference: 23/11/2020 Jeong et al. Clinical characteristics and online mental health care of asymptomatic or mildly symptomatic patients with coronavirus disease 2019. PLoS One.
Summary: This prospective cohort study assessed 234 patients with asymptomatic or mildly symptomatic COVID-19. They used online surveys and the Hospital Anxiety and Depressions Scale to assess levels of anxiety and depression among this cohort. They found that roughly one fifth (19.8%) had anxiety and/or depression and, when compared to those without, had a longer quarantine duration.
Publication date / reference: 17/11/20. Becerra-Munoz et al. Clinical profile and predictors of in-hospital mortality among older patients admitted for COVID-19. Age Ageing.
Summary: The authors aimed to describe clinical characteristics, initial symptoms and management of a cohort of individuals aged >65 (n=1520) hospitalised for COVID-19. Much of this epidemiological paper is not directly related to neurological or neuropsychiatric complications, but n=19 (1.3%) had “an embolic event”, and having dementia (n=70) was independently associated with an eight-fold increased risk of mortality (95%CI=1.45-44.85).
Summary: In their retrospective observational study Kacem et al. presented data on main neurological symptoms in 1034 patients with COVID-19, who were contacted by phone. Six hundred forty-six patients were included in the analysis of which 466 (72.1%) reported neurological symptoms. The most frequent symptom was headache (n=279, 41.1%). Other common symptoms were smell impairment (n = 245, 37.9%), taste impairment (n = 238, 36.8%), myalgia (n = 241, 37.3%) and sleep disturbances (n = 241, 37.3%). Respiratory signs, defined as presence of dyspnea and/or cough, were found to be associated with more frequent and numerous neurological symptoms.
Publication date / reference: 17/11/2020 Abdel-Aziz et al. Subjective Smell Assessment as An Office-based Rapid Procedure In COVID-19 Era. J Craniofac Surg
Summary: This cross-sectional study assessed 480 patients (aged 18-60) who attended an outpatient clinic for subjectively reported olfactory loss on a hard paper-bar using a graded score from 0 to 10.Patients with symptoms of COVID-19 such as fever, cough and/or dyspnea were excluded. Ninety-seven (20.2%) patients reported some level of olfactory loss, of which 88 (90.1%) were SARS-CoV-19 positive on RT-PCR in comparison to only 3 (6%) of 50 control patients who reported no olfactory loss. The authors suggested that subjective olfactory testing could be used as office-based screening procedure for SARS-CoV-19 infection, but it is unclear how this selected clinic population relates to community patients.
Publication date / reference: 17/11/2020 Krishnasamy et al. Clinical Outcomes among Asymptomatic or Mildly Symptomatic COVID-19 Patients in an Isolation Facility in Chennai, India. Am J Trop Med Hyg.
Summary: The authors of this study assessed clinical outcomes among 1,263 asymptomatic or mild symptomatic COVID-19 patients and found fatigue was the fourth most common presenting symptom (10.1%) followed by anosmia (9.4%) or ageusia (8.9%).
Publication date / reference: 21/11/2020. François Lersy et al. Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses. J Neurol.
Summary: This study aimed to investigate the origin of the extensive white matter microhaemorrhages detected by brain MRIs in patients with COVID-19. The authors formulated several hypotheses such as hypoxemia, microangiopathy, and the role of kidney failure which was found to be more severe in the patient group with diffuse microhaemorrhages. The authors concluded that blood–brain barrier dysfunction secondary to hypoxemia and high concentration of uraemic toxins appear to be the primary mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients. However, these remain hypotheses until evaluated further.
Publication date / reference: 21/11/20 van den Borst et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis.
Summary: This prospective cohort study assessed 124 patients who were either discharged from hospital after COVID-19 or referred by a general practitioner after a prolonged (>6 weeks) COVID-19 illness. They were assessed functionally, physiologically and radiologically. They found that there were severe problems in several health domains: 22% had low exercise capacity; 36% had difficulties with mental and/or cognitive function; 69% had ongoing fatigue and 91% of discharged patients still had residual pulmonary parenchymal abnormalities. They state longer follow up studies are warranted to see the trajectory of this disease.
Publication date / reference: 12/11/20 Meppiel et al. Neurological manifestations associated with COVID-19: a multicentric registry. Clin Microbiol Infect.
Summary: The authors of this multicentre, retrospective study assessed 222 COVID-19 patients with novel neurological manifestations across 46 centers in France. The most commonly observed neurological manifestations were COVID-19 associated encephalopathy (30.2%), acute ischaemic cerebrovascular syndrome (25.7%), encephalitis (9.5%) and Guillain-Barré syndrome (6.8%). Neurological manifestations were seen to emerge largely following first COVID-19 symptoms with a median delay of 6, 7, 12 and 18 days in encephalopathy, encephalitis, acute cerebrovascular ischaemia, and Guillain-Barré syndrome respectively.The majority of patients (192) underwent brain imaging and cerebrospinal fluid was analysed in 97 patients.
Publication date / reference: 10/11/2020 Jimenez et al., Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study. BMJ Open
Summary: This single- centre retrospective case series looked at the clinical characteristics of confirmed COVID-19 hospitalised patients (n=1549). Their findings show: presenting symptoms included headache n=133 (8.7%), confusion n=87 (5.7%), anosmia n=41 (3.6%). 178 patients (11.6%, p <0.001) had a background of neurological disease, 57 patients (45.6%, p=0.741) had a background of cerebrovascular disease. The most common risk factor was hypertension (851,55.0%). In terms of outcomes, 11 patients (0.8%) developed a stroke. Of those who died, 59 patients (20.1%) had a background of neurological disease.
Publication date / reference: 24/10/2020 Zhou et al. Cognitive disorders associated with hospitalization of COVID-19: Results from an observational cohort study. Brain Behav Immun.
Summary: This observational cohort study attempted to look at the significance of pre-existing disease in COVID-19. They took 389,620 participants from UK Biobank; 1,091 had COVID-19. They compared 974 medical conditions and 30 blood biomarkers against this diagnosis. They identified the most significant risk factors were Alzheimer Disease, dementia, delirium and other cognitive disorders.
Publication date / reference: 14/10/2020 Lorenzo et al. Residual clinical damage after COVID-19: A retrospective and prospective observational cohort study. PLoS One
Summary: A ‘retrospective and prospective’ observational cohort study examining 185 patients admitted to hospital and followed up between 7th April and 7th of May 2020. They specifically looked at ongoing symptoms after discharge and the development of cognitive impairment or PTSD. 109 patients required follow up from a set criteria. 58 were dyspnoeic, 41 tachypnoeic, 10 malnourished, 106 at risk of malnutrition. 40 had uncontrolled blood pressure, 47 had new onset mild cognitive impairment and PTSD was observed in 41 patients. Use this as a basis that COVID-19 leaves lasting damage and follow up should be implemented for selected patients.
Publication date / reference: 10/09/20. Makda et al. The frequency of neurological symptoms in COVID-19 patients at a tertiary care hospital in Pakistan. Cureus.
Summary: The authors of this cross-sectional study report on neurological symptoms in COVID-19 patients at a teaching hospital in Karachi, Pakistan between April and July 2020. Dizziness and headache were the two most common neurological symptoms, present in 17.5% and 15.7% of patients respectively. Only 7.8% of patients demonstrated impairment in taste and a separate 7.8% displayed impairment in smell. No significant difference was observed when comparing frequency of neurological symptoms between severe and non-severe disease.
Publication date / reference:19/10/20. Hao et al. A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities. Transl Psychiatry.
Summary: A mixed method study of neuropsychiatric sequelae and psychological impact in COVID-19 patients (N=10) compared with matched psychiatric patients (N=10) and matched healthy control (N=10). A significant proportion of COVID-19 patients experienced impulsivity and insomnia compared the two control groups. Half of the COVID-19 patients presented with clinically significant symptoms of PTSD (IES score). COVID-19 patients also had higher levels of depression, anxiety and stress (DASS-21 sub-scores)than control and comparable to psychiatric patients. Face to face interviews were conducted as part of the qualitative analysis. The authors identified three themes from the interviews, 1. emotions experienced by patients after COVID-19 infection; 2) external factors that affected patients’ mood. The findings are limited by the small sample size and cross-sectional design of the study.
Publication date / reference: 07/10/2020. Rifino et al. Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy. J Neurol.
Summary: In this large (n = 1760) retrospective study of hospital admitted covid-19 patients, the authors found that 137 presented with neurological manifestations. Stroke constituted 39%, peripheral nervous disease (e.g. GBS) 25%, and altered mental status 36% of these manifestations. Neurological features alone were the only manifestation of covid-19 illness in 39 patients. Unfortunately, the authors did not go into much detail about how the patients with altered mental status were defined or diagnosed, except five of whom were diagnosed with encephalitis. SARS-CoV-2 was positive in the CSF analysis of two patients with altered mental status. The study did not feature any follow-up data.
Publication date / reference: 5/10/2020. Frontera et al. A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients in New York City. Neurology.
Summary: Prospective, multi-center, observational study to assess neurological symptomatology among hospitalised patients in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. 4,491 patients were admitted in the time frame; 606 patients developed a neurological disorder. Most common diagnoses were: encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), hypoxic/ ischaemic injury (1.4%). There were no patients found to have encephalitis/ meningitis or myelopathy. Myelitis attributable to SARS-CoV-2. They found that patients with neurological complications were: older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores. They also had higher in-hospital mortality and decreased likelihood of discharge home after adjustment.
Publication date / reference: 05/10/20. Carvalho-Schneider et al. Follow-up of adults with non-critical COVID-19 two months after symptoms’ onset. Clin Microbiol Infect.
Summary: The authors of this study followed up 150 COVID-19 patients at days 7, 30, and 60 from symptoms onset from March 17 to June 3, 2020. 68% and 66% of patients displayed at least one persistent symptoms at days 30 and 60 respectively, and this was most commonly anosmia/ageusia with 59% at symptom onset, 28% at day 30 and 30% at day 60. In addition half of patients at day 30 and 40% at day 60 displayed asthenia.
Publication date / reference: 23/09/20. Xiong et al. Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study. Clin Microbiol Infect.
Publication date / reference: 3/9/20. Koh et al. Neurology of COVID-19 in Singapore. J Neurol Sci.
Summary: The authors conducted a prospective multi-centre cohort study of all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. From 47,572 SARS-CoV-2+ patients (median age 34 years, 98% males) they identified 39 patients (0.08%) with neurological disorders. In the entire cohort only 93 patients needed critical care. The reports of neurological syndromes included encephalitis, cerebral venous thrombosis, acute ischaemic stroke or intracerebral haemorrhage, peripheral nervous system disorders and dysautonomia, but only very small numbers of cases of each. This is an unusual result compared to other studies, which the authors speculate might be related to the peculiar demographics of the local outbreak that involved young healthy migrant workers in crowded dormitories, many of whom were asymptomatic or had mild infection. The young age of the sample, near-total male sex, and very low numbers of critical care patients make the study difficult to generalise to other countries with far more severe outcomes. Nevertheless as a whole-population study, the authors report a strikingly low prevalence of COVID-19 associated neurological disorders in Singapore.
Publication date / reference: 21/09/20. Acar et al. Demographic characteristics and neurological comorbidity of patients with COVID-19. Rev Assoc Med Bras (1992).
Publication date / reference: 18/08/20. Iltaf et al. Frequency of Neurological Presentations of Coronavirus Disease in Patients Presenting to a Tertiary Care Hospital During the 2019 Coronavirus Disease Pandemic. Cureus.
Summary: In this cross-sectional study, the authors wanted to ascertain the prevalence of neurological manifestations in patients with COVID-19 who presented to a tertiary medical centre (n=350, mixed inpatients and outpatients, PCR-confirmed). Nearly a fifth of the cohort had neurological manifestations (18.9%). The most common presentations included headache, vertigo, numbness, paraesthesia and altered level of consciousness.
Publication date / reference: 04/08/20. Abenza-Abildúa et al. Neurological complications in critical patients with COVID-19. Neurologica.
Summary: The authors of this retrospective, observational study explored the presence of neurological complications in consecutive patients admitted to ICU with COVID-19 (n=30). Nearly all patients manifested with an acute confusional state (28/30) and half had an acute myopathy (15/30). Other complications included headache, cerebrovascular disease, and encephalopathies/encephalitis. The neuroimaging (MRI, CT and EEG) and CSF analysis findings were described.
Publication date / reference: 15/09/20. García-Moncó et al. Neurological reasons for consultation and hospitalization during the COVID-19 pandemic. Neurol Sci.
Summary: In this prospective cross-sectional study, the authors evaluated the neurological abnormalities in patients with COVID-19 (n=35, PCR-confirmed in 28) who required a neurological consultation at a tertiary centre. In 14 patients, the neurological abnormality was present at admission whereas nervous system complications developed later in the disease course for the remaining 21 patients. The most common presentations were stroke (11/35), encephalopathy (7/35), seizures (6/35) and neuropathies (5/35). Except for neuropathies, all of these complications were associated with severe COVID-19 disease (measured via CURB-65). Concordant with prior research, CSF was negative for viral PCR in all patients. Of potential importance, 14 of the patients had neurological comorbidities and these were distributed fairly evenly across the neurological complications.
Publication date / reference: 11/09/20. Campiglio & Priori. Neurological symptoms in acute COVID-19 infected patients: a survey among Italian physicians. PLoS One.
Summary: The authors of this paper developed an online survey for Italian clinicians involved in the diagnosis and management of COVID-19 patients in which they were asked to use a 4-point Likert scale to rate clinical features from “absent” to “severe”. Responses were received from 126 physicians from 9 different specialities and 10 different regions of Italy. 87.3% of respondents reported neurological symptoms, with the most common being headache, myalgia and taste and smell abnormalities. No difference was noted between reporting by neurologists and non-neurologists. However, clinicians with experience of evaluating >30 COVID-19 patients more frequently reported neurological symptoms.
Publication date / reference: 11/09/20. Coppola et al. Headache in a group of SARS-COVID-19 patients: an observational prospectical study. Neurological Sciences.
Summary: The authors of this Italian prospective study report on a group of 73 COVID-19 patients, all of whom had normal neurological examinations and were free from any clinical sign of neurological impairment. Three male patients reported headache during hospitalisation, two of whom had tension headache whilst one experienced migraine without aura. Tension headaches and migraine without aura were present in three and two female patients respectively. The authors suggest that these findings indicate tension headache may be the more common form of headache in COVID-19.
Publication date / reference: 07/09/20. Kirenga et al. Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda. BMJ Open Respir Res.
Summary: In this prospective cohort study the authors report on clinical characteristics and treatment outcomes of 56 consecutive patients diagnosed with COVID-19 and hospitalised in Uganda. The mean age was only 34 (possibly reflecting the population structure of Uganda); on admission headache was reported by 12.5% and fatigue by 7.1%. Interestingly despite the consecutive recruitment strategy, none of the patients died or even needed ICU.
Publication date / reference: 13/08/20. Zou et al. Clinical Characteristics and Risk Factors for Disease Severity and Death in Patients With Coronavirus Disease 2019 in Wuhan, China. Front Med.
Summary: The authors conducted a retrospective case note review of 121 confirmed and hospitalised COVID-19 patients. Within the broad range of symptoms surveyed across organ systems, “neurological symptoms” were reported by 9.9% of patients at illness onset, and in this small sample were not found to associate significantly with severity or mortality.
Publication date / reference: 25/08/20. Chachkhiani et al. Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization. Clin Neurol Neurosurg.
Summary: In this retrospective observational study, the authors aimed to describe neurological complications at presentation in a large cohort of, mostly African American, patients hospitalised with COVID-19 (n=250, PCR-confirmed) at a university medical centre. Neurological complications were the chief presenting complaint in 34 (14%) of the cohort – most commonly altered mental status, headache and syncope. The authors used logistic regression analysis to ascertain whether patients with neurological complications were at risk of poorer outcomes compared to those without. Interestingly, patients who presented with neurological complaints were at significantly increased risk of remaining in hospital and of increased mortality. Additionally, these patients were at significantly higher odds of requiring intubation. Aside from first presentation, 95 (38 %) had a neurological complication during hospitalisation, of which altered mental status was also the most common. The reliability of the prevalence figures are limited by the retrospective nature of the study but still serves as an important assessment of neurological complications in the understudied African-American COVID-19 population.
Publication date / reference: 17/08/20. Utku et al. Main symptoms in patients presenting in the COVID-19 period. Scott Med J.
Summary: The authors conducted a retrospective case note review of 297 patients with suspicion of COVID-19, and compared symptom profiles between those with (n=143) and without (n=154) a positive PCR test for SARS-CoV-2. The positive group most often had cough, weakness, taste disorder, myalgia, and fever. The COVID-19 negative group most often had cough, weakness, dyspnea, headache and fever. Taste disorder, smell disorder and diarrhea were significantly more frequent in the PCR positive group, suggesting that these symptoms may be relatively more specific for COVID-19.
Publication date / reference: 07/08/20. Yang et al. Pre-pandemic psychiatric disorders and risk of COVID-19: a cohort analysis in the UK Biobank. MedRxiv.
Summary: The authors used the UK Biobank to compare the risks of COVID-19 in 50,815 individuals with pre-existing psychiatric disorders against 370,233 people without such disorders. After correcting for variables including BMI, deprivation, and ethnicity, the authors found significantly increased risks of COVID-19 infections, hospitalisation, and death, in psychiatric patients compared to controls. The authors speculate that “shared pathways” may link psychiatric disorders and infections, such as altered immune responses.
Publication date / reference: 07/08/20. Jeon et al. Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: a nationwide cohort study. MedRxiv.
Summary: The authors used Korean national data to compare the risks of COVID-19 in 33,653 patients with mental disorders against 196,912 controls. They found no significant corrected differences in the odds of a SARS-CoV-2 positive test, and a mixed picture with regards to the risk of clinical severity, but the risk of death was higher among patients with pre-existing psychiatric disorder. The study did not appear to examine specific causes of a higher risk of death and more research will be required to confirm these associations.
Publication date / reference: 31/07/20 Strang et al. Symptom Relief Is Possible in Elderly Dying COVID-19 Patients: A National Register Study. J Palliat Med.
Summary: This study of the Swedish National Palliative Care Register is the first systematic report on symptom prevalence and relief in dying patients outside ICUs. The authors demonstrate higher rates of breathlessness in SARS-CoV-2 patients compared with all deaths registered in 2019 yet equitable levels of anxiety and delirium. Of note is the difficulty in treating these symptoms. Clinicians reported significantly lower success in completely relieving anxiety and delirium in those with COVID-19 compared with the Register for 2019.
Publication date / reference: 05/08/20 Poncet-Megemont et al. High prevalence of headaches during COVID-19 infection: a retrospective cohort study. Headache.
Summary: This retrospective cohort study included 139 patients with COVID-19 who were interviewed one month after resolution of fever and dyspnoea. The authors found that 59% (82/139) of patients reported new headaches during the acute phase of illness, though only 3.6% (5/139) reported ongoing headaches. Anosmia and ageusia were common and reported in 60.4% (84/139) and 58.3% (81/139) of cases respectively, and were seen to persist in 14.4% (20/139) and 11.5% (16/139) of patients. No association was identified between headaches and anosmia, ageusia or disease severity.
Publication date / reference: 03/08/20 Studart-Neto et al. Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital. Arq Neuropsiquiatr.
Summary: This retrospective study was conducted between March 23rd and May 23rd 2020, during which time 1,208 confirmed COVID-19 patients were admitted to a dedicated COVID-19 hospital in Brazil, 7.4% (89/1,208) of whom required inpatient neurological consultations. Of these patients, 44.4% (40/89) were diagnosed with encephalopathy, 12.3% (11/89) with stroke, 9.0% (8/89) with previous neurological disease, 9.0% (8/89) with seizures, 5.6% (5/89) with neuromuscular disease and 3.4% (3/89) with other acute cerebral lesions.
Publication date / reference: 06/08/20 Agarwal et al. Neurological manifestations in 404 COVID-19 patients in Washington State. J Neurol.
Summary: In this retrospective study, Agarwal and colleagues reviewed the medical records of 404 patients with COVID-19 (PCR-confirmed) and found neurological manifestations in 73% of the cohort. Half of the patients in this sample had CNS symptoms at presentation, the most common being altered mental status, headache and dizziness. However, over half of the patients with altered mental status had pre-existing dementia. Acute neurological symptoms were reported in 21.3% of patients, which was predominately altered mental status and stroke was found in only 0.7% of the cohort. Peripheral neurological symptoms, including myalgia and taste/smell disturbance, were reported in 40% of patients. Reasons for why this study detected much higher prevalences of neurological manifestations were not discussed.
Publication date / reference: 06/08/20. Kantonen et al. Neuropathologic features of four autopsied COVID-19 patients. Brain Pathol.
Summary: In this correspondence, Kantonen and colleagues reported the neuropathological findings from four autopsied patients with COVID-19 (PCR-confirmation was unclear). Two of the patients had neurological symptoms, including reduced level of consciousness and anosmia respectively. Regarding the former patient, a rather complicated case was presented of a 34 year old man diagnosed with Parkinson’s disease who rapidly deteriorated with respiratory distress due to COVID-19 and was unresponsive on ICU. The autopsy findings from this patient included severe ischaemic injury whereas for the other patients only mild-moderate hypoxia-associated changes were found. There were no findings of encephalitis/meningitis and PCR could not detect SARS-COV-2 in brain tissue.
Publication date / reference: 02/08/20 Morshed et al. Clinical manifestations of patients with coronavirus disease 2019 (COVID-19) attending at hospitals in Bangladesh. MedRxiv preprint.
Summary: The authors of this cross-sectional study report the clinical features of 103 RT-PCR confirmed non-critical care COVID-19 patients across three dedicated COVID-19 hospitals in Bangladesh. Fatigue was noted in a large proportion of patients (68%). Altered sensation of taste or smell was reported in 35.0% of patients, whilst myalgia and headache were each reported in 32% of patients.
Publication date / reference: 30/07/20 Halpin et al. Post-discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation. J Med Virol.
Summary: Despite concerns about possible long-term physical and mental health consequences of COVID-19, the nature and prevalence of post-COVID-19 symptoms after hospital discharge have not been well studied. Using a prospective cross-sectional design the authors conducted telephone-based follow-up screening of 100 patients who had required ICU care (n=32) or general ward level care (n=68) and who were at least four weeks post-discharge. Fatigue of at least moderate severity was reported by 41%, concentration problems by 22%, and PTSD symptoms of at least moderate severity by 10%. Most of the ICU group and a minority of the ward group remained off work sick. The authors conclude by calling for needs-focused rehabilitation services to be planned for, and delivered, over an extended period.
Publication date / reference: 08/07/20 Paterson et al. The Emerging Spectrum of COVID-19 Neurology: Clinical, Radiological and Laboratory Findings. Brain
Summary: This retrospective cohort study described the clinical, laboratory and radiological features of patients (n=43) referred to a COVID-19 neurology multidisciplinary team meeting. Based on the findings, patients were grouped into five categories: (i) para-infectious encephalopathy with delirium (n=ten), (ii) inflammatory CNS syndromes (two with encephalitis, nine with ADEM), (iii) ischaemic stroke (n=eight, of which four had pulmonary thromboembolism), (iv) peripheral neurological disorders (n=eight, seven with GBS), (v) miscellaneous (n=five, including myopathy, cranial nerve palsy, brain abscess).
Publication date / reference: 08/07/20 Hwang et al. Neurological Diseases as Mortality Predictive Factors for Patients With COVID-19: A Retrospective Cohort Study. Neurol Sci.
Summary: Retrospective cohort study of patients admitted to hospital with COVID-19 with an outcome of death or discharge between 1st February and 25th March (n=103, of whom 26 had died). The authors examined for an association between medication history / medical comorbidities and outcome. Multivariable logistic regression identified age >70, chronic lung disease, and Alzheimer’s Disease as independent predictors of death. Regression analyses with limited group sizes must be interpreted very cautiously given the risk of model over-fitting, but the study is the first to tentatively identify AD as an independent prognostic variable.
Publication date / reference: 02/07/20 Vacchiano et al. Early neurological manifestations of hospitalized COVID-19 patients. Neurol Sci
Summary: This is a prospective cohort study of n=108 hospitalised COVID-19 patients, followed for 30 days from the point of admission. Structured questionnaires were administered by telephone to assess neurological symptoms. The median onset of neurological manifestations was 1-3 days, with the most common being gustatory disorders (61%), headache (43%) and olfactory disorders (37%). Olfactory disorders were associated with milder disease and more often reported by patients with gustatory disorders. Both olfactory and gustatory disorders persisted over the follow-up period, despite reported improvements in severity. Most patients reporting headaches described tension-type symptoms. The authors acknowledge the limitations of the study, including the relatively small sample size, geographical specificity, inclusion of only hospitalised patients, and the short follow-up period.
Publication date / reference: 01/07/20 Abdel-Mannan et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol.
Summary: In a retrospective analysis of n=27 children who were hospitalised with COVID-19 infection, the authors detected new-onset neurological symptoms (most commonly encephalopathy and headache) in n=4 patients (14.8%). All four patients had signal changes in the splenium of the corpus callosum on neuroimaging, and required intensive care admission. The authors highlight the potential for children to display new neurological symptoms involving both the central and peripheral nervous systems with splenial changes on imaging, in the absence of respiratory symptoms.
Publication date / reference: 25/6/20 (preprint 15/5/20) Varatharaj et al. UK-wide surveillance of neurological and neuropsychiatric complications of COVID-19: The first 153 patients. Lancet Psych
Summary: In first 3 weeks of UK-wide surveillance system 153 cases were notified with median (range) age 71 (23-94) years. 77 (62%) had a cerebrovascular event: 57 (74%) ischemic strokes, nine (12%) intracerebral hemorrhages, and one CNS vasculitis. The second most common group were 39 (31%) who had altered mental status, including 16 (41%) with encephalopathy of whom seven (44%) had encephalitis. The remaining 23 (59%) had a psychiatric diagnosis of whom 21 (92%) were new diagnoses; including ten (43%) with psychosis, six (26%) neurocognitive (dementia-like) syndrome, and 4 (17%) an affective disorder. Cerebrovascular events predominated in older patients. Conversely, altered mental status, whilst present in all ages, had disproportionate representation in the young (♦).
Publication date / reference: 25/06/20 Karadaş et al. A prospective clinical study of detailed neurological manifestations in patients with COVID-19. Neurol Sci
Summary: This prospective study of 239 patients with COVID-19 revealed that 34.7% (n=83) had neurological findings and that these patients had significantly higher levels of D-dimer, compared to those without neurological manifestations. The most common finding was headache (27.6%) and these patients had a significantly higher level of IL-6 compared to those without headache (possibly implicating the acute phase response in the pathogenesis of headache in COVID-19).
Publication date / reference: 17/06/20 Moro et al. The international EAN survey on neurological symptoms in patients with COVID-19 infection. Eur J Neurol.
Summary: The European Academy of Neurology surveyed physicians about neurological symptoms in patients with COVID-19. From 2343/4199 full responses, the commonest neurological observation was headache (reported by 61.9% of responding physicians), followed by myalgia, anosmia, dysgeusia, impaired consciousness, psychomotor agitation, encephalopathy and acute cerebrovascular disorders. Just under 1/3 physicians had also encountered CSF and/or EEG abnormalities. Findings are limited by the modest completion rate and potential selection or reporting bias.
Publication date / reference: 17/06/20 Nalleballe et al. Spectrum of Neuropsychiatric Manifestations in COVID-19. Brain Behav. Immun.
Summary: The TriNetX database, a global collaborative platform containing 40,469 patients with COVID (76% from the US), was analysed to explore the presence of neuropsychiatric manifestations (22.5%, n=9086, had a neuropsychiatric ICD-10 diagnosis). The most common neurological findings were headache (3.7%), sleep disorders (3.4%), encephalopathy (2.3%) and myalgia (2.0%). Psychiatric disturbances included anxiety and related disorders (4.6%), mood disorders (3.8%) and suicidal ideation (0.2%). Limitations include: no description of CSF or neuroimaging investigations and database analysis was solely based on diagnostic codes and did not use individual patient data.
Publication date / reference: 03/06/20 Pinna et al. Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline. J Neurol Sci
Summary: A retrospective observational case series of 50 patients hospitalised with COVID who were evaluated by neurological services at a tertiary care centre. Common neurological findings included encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), headache and cognitive abnormalities (both n=12). Patients with neurological findings that were documented after initial assessment had a more severe clinical course than those with abnormalities on admission. Findings are limited by selection bias (cases were only included if they had been evaluated by neurology service) and the retrospective approach.
Publication date / reference: 01/06/20 Romero-Sánchez et al. Neurologic Manifestations in Hospitalized Patients With COVID-19: The ALBACOVID Registry. Neurology.
Summary: Single-centre review of 841 patients hospitalized with COVID-19. 57% developed neurological symptoms. Myalgias and headache were common. Anosmia (5%) and dysgeusia (6%) occurred as the first symptom in 60%. Altered consciousness occurred in 19%. Myopathy (3%), dysautonomia (3%), cerebrovascular diseases (2%), seizures (1%), movement disorders (1%), encephalitis (n=1). Neurological complications were the main cause of death in 4.1% of all deceased study subjects(♦).
Publication date / reference: 30/05/20 Lapostelle et al. Clinical Features of 1487 COVID-19 Patients with Outpatient Management in the Greater Paris: The COVID-call Study. Intern Emerg Med.
Summary: In addition to dry cough and fever 1487 outpatients meeting COVID-19 WHO criteria reported body aches/myalgia (57%), headache (55%), and asthenia (60%); shortness of breath (32%) and ear-nose-throat symptoms such as anosmia (28%) and ageusia (28%).
Publication date / reference: 28/05/20 Scullen et al. COVID-19 Associated Encephalopathies and Cerebrovascular Disease: The New Orleans Experience. World Neurosurg.
Summary: Single centre retrospective cross-sectional study of ITU patients with SARS-CoV-2 (n=76). 27 patients had new neurological disease. All but one patient with neurological involvement developed altered mental status.85% demonstrated radiographic or electrographic evidence of neurologic disease.74% were diagnosed with COVID-19 associated encephalopathy, 7% with COVID-19 associated acute necrotizing encephalopathy, and 19% with COVID-19 associated vasculopathy. Radiological diagnoses infer the importance of neuroimaging in our COVID-19 patients, but cases limited to a single centre so not reflective of the wider population.
Publication date / reference: 28/05/20 Radmanesh et al. Brain Imaging Use and Findings in COVID-19: A Single Academic Center Experience in the Epicenter of Disease in the United States. JNR Am J Neuroradiol.
Summary: Retrospective case series in New York of CT/MRI findings in SARS-CoV-2 confirmed patients (n=242). Imaging was most commonly performed for altered mental status, syncope/fall and focal neurologic deficit. The most common findings were nonspecific white matter microangiopathy (55.4%), chronic infarct (19.4%), acute or subacute ischemic infarct (5.4%), and acute haemorrhage (4.5%)(♦).
Publication date / reference: 26/05/20 Graham et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes. Preprint MedRxiv.
Summary: Data from UK nursing homes on patients with SARS-CoV-2 (n=126 of 313 tested). The authors highlight a 203% increase in all-cause mortality when compared with preceding two years with 43% of positive samples in asymptomatic residents. They also demonstrate high rates of atypical symptoms like anorexia (27%) and confusion (34%)(♦).
Publication date / reference: 23/05/20 Pilotto et al. COVID-19 impact on consecutive neurological patients admitted to the emergency department. MedRxiv (preprint).
Summary: Retrospective study of 505 patients with neurological symptoms who were seen in ED. 147 patients tested positive for SARS-CoV-2. Positive patients had higher rates of stroke (34.7% vs 29.3%), encephalitis/meningitis (9.5% vs 1.9%) and delirium (16.3% vs 5.0%)(♦).
Publication date / reference: 20/05/20 Yang et al. Analysis of the clinical characteristics, drug treatments and prognoses of 136 patients with coronavirus disease 2019. J Clin Pharm Ther.
Summary: Retrospective, single‐centre, case series (n=136 patients) who were diagnosed with SARS-CoV-2. Amongst the commonly reported symptoms of cough and fever, 36% patients demonstrated insomnia, many of whom were otherwise asymptomatic.
Publication date / reference: 19/05/20 Jain et al. COVID-19 Related Neuroimaging Findings: A Signal of Thromboembolic Complications and a Strong Prognostic Marker of Poor Patient Outcome. J Neurol Sci.
Summary: Retrospective cohort study of 3218 SARS-CoV-2 patients, of which 14% had neuroimaging. Stroke was the most commonly identified abnormality, found in 1.1% of hospitalised patients. These findings were a strong predictor of poor mortality.
Publication date / reference: 19/05/20 Cummings et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. The Lancet.
Summary: Prospective observational study characterising the epidemiology and clinical course of 257 critically ill patients with confirmed SARS-CoV-2 admitted during the first month of the New York City’s outbreak. Although shortness of breath and fever dominated the first symptoms, altered mental state was seen in 9% of those on presentation to hospital.
Publication date / reference: 30/04/20 Lechien et al. Clinical and Epidemiological Characteristics of 1,420 European Patients with mild-to-moderate Coronavirus Disease 2019. J Int Med
Summary: Prospective observational study of 1420 patients in European hospitals with mild-to-moderate COVID-19 infection. Headache was seen in 70.3%. There were also reports of visual acuity reduction (N=6), rotatory vertigo (N=6), and tinnitus (N=5).
Publication date / reference: 28/04/20 Docherty AB et al. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. medRxiv (preprint).
Summary: Prospective observational cohort study of 16,749 UK patients with COVID-19 which reports of headache (~10%), seizures (~1%), and confusion (~25%) upon presentation to hospital.
Publication date / reference: 15/04/20 Zhu J, Ji P, Pang J, et al. Clinical characteristics of 3,062 COVID-19 patients: a meta-analysis. J Med Virol
Summary: A meta-analysis of epidemiological data (3,062 COVID-19 patients). In total, 15.4% patients experienced headache.
Publication date / reference: 30/03/20 Borges do Nascimento I et al. Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis. J Clin Med
Summary: Meta-analysis;12% of included COVID-19 positive patients had headache.
Publication date / reference: 26/03/20 Chen T et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. Brit Med J
Summary: Retrospective case series of 274 patients with COVID-19 who had died. In total, 23 (20%) of developed hypoxic encephalopathy after diagnosis of COVID-19.
Publication date / reference: 21/02/20 Yang X et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med.
Summary: Retrospective case series of 52 critically ill patients found headache in 6%.
Publication date / reference: 19/02/20 Xu XW et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. Brit Med J.
Summary: Retrospective case series of 62 patients admitted to hospital with laboratory confirmed SARS-CoV-2 infection found headache in 21 (34%).
Publication date / reference: 07/02/20 Wang D et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. J Am Med Assoc.
Summary: Retrospective case series of 138 hospitalized patients found dizziness in 9% and headache in 7%.
Publication date / reference: 29/01/20 Chen N et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet.
Summary: Retrospective case series of 99 patients. Confusion in 9%, headache in 8%.
Publication date / reference: 24/01/20 Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet.
Encephalopathy, Encephalitis, Meningoencephalitis
Publication date / reference: 13/04/2021. Duan K, et al., Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19. Neurobiol Stress.
Summary: The authors of this study used source-based morphometry (SBM) analysis to investigate the alterations in covarying gray matter volume (GMV) patterns derived from computed tomography scans, obtained from 120 neurological patients. 58 COVID-19 patients and a control group of 62 patients matched for age, gender and diseases (without COVID-19 infection) participated in this study.
SBM identified the significant association between reduced GMV in superior/medial/middle frontal gyri and higher level of disability (modified Rankin Scale), at discharge and during the 6 month follow-up period (despite CVD control). Reduced GMV in superior/medial/middle frontal gyri was observed in patients receiving oxygen therapy (compared to those not received oxygen therapy). Significant reduction in GMV in inferior/middle temporal gyri and fusiform gyrus was observed in patients presented with fever (compared to patients without fever). GMV reduction in superior/medial/middle frontal gyri was also observed in patients with agitation (compared to patients without agitation). No significant GMV differences in any brain region were identified between patients with or without COVID-19 infection.
The study has determined that fever or lack of oxygen caused by COVID-19 infection may subsequently lead to disruption of the frontal-temporal network.
Publication date / reference: 31/03/2021 Branco de Oliveira MV et al., Encephalopathy responsive to thiamine in severe COVID-19 patients. Brain Behav Immun Health.
Summary: This retrospective case series (n=15) investigated responses to intravenous thiamine treatment in patients with COVID-19-associated Wernicke Encephalopathy. The authors searched electronic medical records for comorbidities and evaluated functional neurological outcomes using the modified Rankin scale. All patients had encephalopathy, and 10/15 had at least one other neurological manifestation. All patients showed significant improvements in neurological manifestations between two to five days after intravenous thiamine replacement. The authors concluded that thiamine deficiency may be an aetiology of encephalopathy in severe COVID-19 patients, and its treatment may improve neurological outcomes.
Publication date / reference: 25/02/21 Niguet et al. Neurophysiological findings and their prognostic value in critical COVID-19 patients: An observational study. Clin Neurophysiol.
Summary: This observational study describes the EEG patterns of 33 critical COVID-19 patients (all were admitted to ICU) following discontinuation of sedation. Those who were not responsive to EEG had further measurements of omesthesic evoked potentials and brainstem auditive evoked potentials. Overall 85% showed some level of background activity. 42% of cases were unreactive while rhythmic or periodic delta waves were found in 61% of cases. This later finding was associated with clinical outcome on day 14- consistent with encephalopathy.
Publication date / reference: 16/03/21 Frontera et al. Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19. Neurocrit Care.
Summary: This study aimed to estimate the prevalence of Toxic metabolic encephalopathy (TME) in a cohort of 4491 hospitalised COVID-19 patients at multiple centers in New York. Of these 12% had TME of which 78% already had encephalopathy on admission. Compared with those without TME, patients with TME were older, had dementia or psychiatric history, were more often intubated, had a longer hospital length of stay, and were less often discharged home. After adjustment for confounding factors TME was still associated with an increased risk of in-hospital mortality.
Publication date / reference: 30/03/2021 Ugine et al., COVID‐19 encephalopathy: clinical and neurobiological features J Med Virol
Summary: In this study, authors described a series of patients with COVID‐19 encephalopathy, highlighting its phenomenology and its neurobiological features. 707 patients infected by SARS‐CoV‐2 and 31 consecutive patients with acute encephalopathy were included in this series. Severity of the COVID‐19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases were defined on a RASS < ‐3 at worst presentation. Severe form of this COVID‐19 encephalopathy presented more often with headache. MRI abnormalities were found in 92% of the sample.
Publication date / reference: 26/03/2021 Uginet et al., Cerebrovascular Complications and Vessel Wall Imaging in COVID-19 Encephalopathy—A Pilot Study. Clin Neuroradiol
Summary: This pilot study reports a series of patients (n=34) with COVID-19 encephalopathy who underwent standard brain magnetic resonance imaging (MRI) during the acute symptomatic phase of infection. Diffusion-weighted imaging, MR angiography and susceptibility-weighted images, high-resolution vascular black blood sequences were also used to explore the brain vasculature. 85% (n=29) patients with COVID-19 encephalopathy had circular enhancement and thickening of the basilar and vertebral arteries without any correlation to ischemia or microbleeds, This high prevalence of vascular changes suggests an inflammatory mechanism may underlie the encephalopathy.
Publication date / reference: 3/2021. Sanz-Canalejas et al. Lesson of the month: Severe leukoencephalopathy by SARS-CoV-2. Clin Med (Lond).
Summary: Two cases are presented where patients receiving treatment in ICU for severe COVID-19, presented with persistently depressed mental status, following the withdrawal of sedation, alongside evidence of leukoencephalopathy on MRI. Both patients improved clinically, with one being transferred to a different hospital, and the other being discharged home, however, these patients were not followed up further.
Publication date / reference: 09/03/2021 Fragiel et al., Incidence, clinical characteristics, risk factors and outcomes of meningoencephalitis in patients with COVID-19. Eur J Clin Microbiol Infect Dis.
Summary: This was a retrospective case-control study, investigating the differences between COVID-19 patients with ME (meningoencephalitis) and two control groups: non-COVID patients with ME and non-COVID-19 patients without ME. Incidence, clinical characteristics, risk factors and ME outcomes were all investigated. Despite ME being an unusual presentation of COVID (less than 0.05% total cases), it was more than four times frequent than in the non-COVID population. COVID-ME patients had a higher unadjusted in-hospital mortality than non-COVID-ME patients.
Publication date / reference: 04/01/21. Pilotto et al. SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses. Clin Infect Dis.
Summary: The authors of this mechanistic study evaluated the CSF correlates of SARS-CoV-2 encephalitis. They tested an extensive battery of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-microglobulin) in three groups: (i) PCR-confirmed SARS-CoV-2 infection and probable encephalitis (COV-Enc) n=13, (ii) encephalitis without SARS-CoV-2 infection (ENC) n= 21 and (iii) healthy controls (HC) n=18. The cytokine profile of the COV-Enc group included raised IL-8, IL-6, TNF- α, and β2-microglobulin and astrocyte/microglia markers (GFAP, sTREM-2, YKL-40) levels. . Markers of neuronal damage (NfL and t-tau) were only abnormal in very severe COVID-19 (n=5, n=6 respectively). CSF protein levels were mildly increased in the COV-Enc group which could be indicative of BBB dysfunction.
Publication date / reference: 07/12/20. Lopes et al. Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature. Arq Neuropsiquiatr.
Summary: The authors presented two cases of COVID-19 patients who displayed delayed recovery of consciousness following sedation withdrawal in ITU. MRI scans showed multifocal centrum semiovale lesions, suggestive of demyelination. Interestingly, cerebrospinal fluid PCR for SARS-CoV-2 was negative in both cases. The authors called for further study into the role of viral infection and immune-mediated changes in neurological manifestations of COVID-19.
Publication date / reference: 03/12/20202. Assunção et al. COVID-19-Associated Acute Disseminated Encephalomyelitis–Like Disease. American Journal of Neuroradiology
Summary: This letter from the American Journal of Neuroradiology discusses peculiar brain MRI patterns of two COVID-19 hospitalized patients as reported by Toledano-Massiah et al in “Unusual Brain MRI Pattern in 2 Patients with COVID-19 Acute Respiratory Distress Syndrome.” At the time of the MRI scanning, the first patients (49 year old male) showed clinical improvement of COVID -19 thirty days after hospitalization, and the second patient (9 year old child) had a negative RT-PCR for SARS-CoV-2. The radiological findings in the first patient demonstrated nodular and oval hyperintensities in the deep and periventricular cerebral white matter, splenium of the corpus callosum and pons. For the second patient, the oval hyperintensities affected the subcortical white matter, the infratentorial fossa of the middle cerebellar peduncles and the posterior arm of the right inner capsule. The lesions had an open ring enhancement pattern in the middle cerebellar peduncle. While the underlying pathophysiology of these lesions need further investigation, the clinical radiology presentation suggests the development of an auto-immune response that manifested as Acute disseminated encephalomyelitis (ADEM) in these patients. The authors argue that the development of ADEM like symptoms during an active infection in patient 1 and post the infective stage in tpatient 2 consolidates the inflammatory mechanism hypothesis in that the SARS-CoV-2 infection triggered an autoimmune response in these two patients.
Publication Date/Reference: Sep-Oct 2020. McCuddy et al. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 Infection: A Case Series. Neurol India.
Summary: The authors report on three patients who developed ARDS secondary to COVID-19, requiring ventilatory support. Following clinical deteriorations, MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. Each patient was treated with intravenous corticosteroids and one improved markedly. The other two had minimal response and no further improvement after IVIG.
Publication date / reference: 16/10/20. Cao et al. Severe COVID-19 related encephalitis can respond to immunotherapy. Brain.
Summary: In this case series of five patients with severe COVID-19-related encephalitis, three were seen to improve clinically with plasma exchange and corticosteroid therapy. The authors suggest that the lack of prior neurological symptoms as well as MRI abnormalities and absence of SARS-CoV-2 in CSF indicate an underlying immune process rather than direct viral neuro-invasion.
Publication date / reference: 01/10/20. Koutroumanidis et al. Alpha coma EEG pattern in patients with severe COVID-19 related encephalopathy. Clin Neurophysiol.
Summary: This retrospective observational study conducted at St Thomas’ Hospital in London analysed the EEGs of 19 patients with confirmed positive SARS-CoV-2 infection. Overall sickness severity was high: Median SOFA score on admission was eight and worsened to 10. Four patients had seizures and two suffered cardiac arrests due to hypoxaemia prior to EEGs being performed. In 13 patients, EEG was performed because encephalopathy was suspected. Out of the 19 patients, features of encephalopathy were detected in 17, complete electro-cerebral silence was found in one patient and one patient was normal. The authors concluded that they had found severe encephalopathy EEG abnormalities at/around the time of peak disease severity in 13 patients with laboratory-confirmed severe COVID-19.
Publication date / reference: 08/10/20 Muccicoli et al. Intravenous immunoglobulin therapy in COVID-19-related encephalopathy. J Neurol.
Summary: This retrospective case series of 5 patients provides a cursory report on the safety and efficacy of IVIg in encephalopathic patients with COVID-19. Neuropsychiatric manifestations in this group included impaired consciousness along with an array of pyramidal and extrapyramidal signs. EEGs showed diffuse slowing in all patients. IVIg was started at a mean of 29.8 days following symptom onset and in all patients there was recovery both clinically and neurophysiologically. To note tociluzamab and methylprednisolone were also given during the disease course.
Publication date / reference: 01/10/20. Tyson et al. Altered mental status in 71 deaths due to COVID-19. Int J Neurosci.
Summary: Via chart review of 506 consecutive patients with SARS-CoV-2 infection, the authors identified 71 deaths, two-thirds of whom had been admitted from nursing or care homes. Altered mental status was defined as “chart documentation of mental status change, confusion, delirium, decreased level of consciousness, impaired consciousness, somnolent, obtunded, encephalopathy, unresponsive and/or coma”. Altered mental status was the most common neurologic symptom at admission and noted in 47/71 patients who subsequently died. Seven percent of this sample presented with altered mental status without respiratory symptoms.
Publication date / reference: 21/09/20. Umapathi et al. Encephalopathy in COVID-19 patients; viral, parainfectious, or both? eNeurologicalSci.
Summary: The authors describe the clinical, laboratory and radiological features of 3 critically ill patients with COVID-19 who developed severe encephalopathy. One recovered with cognitive deficits and the others died. MRI showed multifocal abnormalities predominantly in the cerebral white matter, with varying involvement of the grey matter, brainstem and spinal cord. The authors felt themselves “not able to convincingly show, from microbiological as well as immunological evaluation, if the effects of COVID-19 on these patients’ nervous system were a direct consequence of the virus, proinflammatory-thrombotic state or a combination.”
Publication Date/Reference: 05/10/2020. Eric M Liotta et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol.
Summary: This retrospective study aimed to characterise neurological manifestations, risk factors, and outcomes in COVID-19 patients admitted in hospital. 509 patients were examined for neurologic manifestations, and the authors concluded that most hospitalized patients have neurological manifestations. Furthermore, patients with neurologic manifestations experienced longer hospitalization with increased morbidity and mortality associated with encephalopathy.
Publication date / reference: 25/09/20. Alexopolous et al. Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients. Neurol Neuroimmunol Neuroinflamm.
Summary: Several recent case series of CSF analysis have found no evidence of SARS-CoV-2 RNA in cerebrospinal fluid (CSF) of COVID-19 patients. In a new case series of eight critically ill COVID-19 patients with encephalopathy, Alexopolous et al. additionally tested CSF and serum for anti-SARS-CoV-2 IgG antibodies. One patient had presented with agitated confusion; none of the others had neurological symptoms on admission. Routine CSF analyses were normal and autoimmune encephalitis antibody tests were negative in all cases. Once more SARS-CoV-2 was not detectable in CSF by PCR. All patients had high titres of anti–SARS-CoV-2 IgG antibodies in serum however, and these antibodies were detectable in the CSF of all patients and in none of 20 control CSF samples from other CNS diseases. In four of the eight patients CSF antibody titers were very high; CSF in three of these patients was also positive for 14-3-3 protein suggesting the onset of neurodegeneration. The authors presented evidence of BBB breakdown and – in one patient – intrathecal synthesis of anti–SARS-CoV-2 IgG. They speculated that antibodies entering or produced in the CNS compartment might directly cause neurologic damage by mobilizing neuroinflammatory responses.
Publication date / reference: 01/09/20. Shah et al. Acute encephalopathy is associated with worse outcomes in COVID-19 patients. Brain Behav Immun Health.
Summary: The authors of this study used TriNetX, a large COVID-19 database, and included hospitalised COVID-19 patients since January 20 who had encephalopathy based on ICD-10 coding. Of the 12,601 patients with COVID-19, 1092 (8.7%) developed acute encephalopathy. Those patients who had sustained acute encephalopathy tended to be older and had a higher prevalence of medical comorbidities. In addition, after propensity score-matching for comorbidities, patients with acute encephalopathy were significantly more likely to require critical care or intubation, and they had a significantly greater 30-day mortality.
Publication date / reference: 01/09/20. Tuma et al. Clinical, cerebrospinal fluid and neuroimaging findings in COVID-19 encephalopathy: a case series. MedRxiv (pre-print, not peer reviewed)
Summary: In this retrospective observational study, the authors aimed to describe the clinical, neuroimaging and laboratory findings of patients with COVID-19 encephalopathy (n=43, PCR or Ab-confirmed). The severity of encephalopathy was varied: 13 were severe, 18 were moderate and 12 were mild. Neuroimaging findings mostly showed non-specific changes although four had suffered an acute stroke. CSF analysis was mostly unremarkable except for two patients with elevated WCC. Interestingly, the severity of encephalopathy correlated with a higher probability of death during hospitalisation. However, cause of death was not reported and the cross-sectional nature of this study cannot determine causality or the direction of relationship between encephalopathy and mortality.
Publication date / reference: 27/08/20. Perrin et al. Cytokine release syndrome-associated encephalopathy in patients with COVID-19. Eur J Neurol.
Summary: The authors report a longitudinal clinical, laboratory, and imaging characterization of five patients with severe COVID-19 and renal failure who developed severe neurological disturbances. The clinical presentation of CNS involvement included confusion, agitation, tremor, impaired consciousness, dysexecutive syndrome, pyramidal syndrome, cerebellar ataxia, cranial nerve palsy, dysautonomia, and central hormonal dysfunction (mainly in the form of hypothyroidism). The systemic presentation reflected cytokine release syndrome – fever, headache, myalgia, occasional rash, respiratory failure, and occasionally multiorgan failure). SARS-CoV-2 was undetectable in the CSF in all patients. The study is limited by the very small sample size.
Publication date / reference: 30/07/20. Poloni et al. Prevalence and prognostic value of Delirium as the initial presentation of COVID-19 in the elderly with dementia: An Italian retrospective study. EClinicalMedicine.
Summary: Retrospective case-note review aiming to determine the prevalence of delirium as the sole manifestation of confirmed COVID-19 in 57 elderly patients with dementia, and its prognostic value for mortality. Participants who developed delirium at onset of COVID-19 without manifesting any of the typical symptoms (e.g. fever, cough, dyspnoea) were compared to control patients who did have those symptoms. Delirium was assessed using the CAM. 21/57 patients showed sudden onset behavioural changes, with fever or other typical symptoms appearing 24–96 after delirium onset in 19 of these patients. 14/57 patients died, of whom 11 showed delirium as the initial onset. The authors concluded that presenting delirium increased the risk for COVID-19 mortality.
Publication date / reference: 13/08/20. Kihira et al. Imaging Features of Acute Encephalopathy in Patients with COVID-19: A Case Series. AJNR Am Neuroradiol.
Summary: Kihira and colleagues report 5 cases of varying imaging presentation of acute encephalopathy in patients with COVID-19. They report features including leukoencephalopathy, diffusion restrictions involving grey and white matter, micro-haemorrhages and leptomeningitis. The cases reported are varied and complex, and direct causal link cannot be established between COVID-19 and the imaging appearances, the authors accepts that causes for these can be wide-ranging and multifactorial, that as well as direct infectious encephalitis, post-viral encephalitis, hypoxia and critical illness related encephalopathy all remain under consideration.
Publication date / reference: 20/08/20. Marengoni et al. The impact of delirium on outcomes for older adults hospitalised with COVID-19. Age Ageing.
Summary: Marengoni and colleagues conducted a retrospective analysis to determine the prevalence and outcome of delirium in older adults hospitalised with COVID-19 (n=91 all PCR-confirmed, >70-years-old). Based on assessment by two geriatricians and use of DSM-V criteria, 25 patients (27.5%) had delirium. Of these patients, 18/25 died compared to 21/66 without delirium. To quantify an increased risk of mortality, the authors conducted a multivariate logistic regression model which showed that patients with delirium were four times more likely to die during admission than those without. As expected, patients with delirium were more likely to be older and frail (at admission). It would be useful to understand the premorbid state and the prevalence of dementia in this sample, to determine the differences in risk and outcome in patients with an underlying cognitive disorder.
Publication date / reference: 08/08/20. Helms et al. Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients. Crit Care.
Summary: Prospective cohort study of 140 COVID-19 patients admitted consecutively to ICU for ARDS, describing the incidence of delirium or abnormal neurological examination, and comparing outcome against COVID-19 patients in the same cohort without such factors. The prevalence of delirium and/or abnormal neurological examination was 114/140 (84.3%). EEGs mainly revealed nonspecific abnormalities commonly seen in sedated patients. MRI showed, variously, enhancement of subarachnoid spaces, intraparenchymal abnormalities, and perfusion abnormalities. LP/CSF was abnormal in 18/25 cases with a high frequency of inflammatory markers. Delirious patients had a longer ICU stay and perhaps a higher risk of premature auto-extubation, but there was no evidence of elevated mortality compared to non-delirious patients.
Publication date / reference: 11/08/20. Huang et al. Pearls and Oy-sters: Leukoencephalopathy in critically ill COVID-19 patients. Neurology.
Summary: The authors report a small case series of four patients with leukoencephalopathy following COVID-19 infection. They discuss possible mechanisms including hypoxic ischemic injury, microvascular thrombosis secondary to hypercoagulability and endothelial damage. They urge clinicians caring for critically ill patients with COVID-19 who have encephalopathy, to obtain an MRI brain before attributing prolonged coma to infection or toxic-metabolic conditions.
Publication date / reference: 14/07/20 Mcloughlin et al. Functional and cognitive outcomes after COVID-19 delirium. Eur Geriatr Med.
Summary: The authors examined the prevalence of delirium in patients hospitalised with COVID-19, and quantified its association with mortality and cognitive and physical impairments at 4 weeks. To do this, they conducted a single-centre prospective cohort study of hospitalised patients with a confirmed diagnosis of COVID-19 on a single day (19th April; n=71; 46 of whom were in HDU or ICU). The primary outcome was all-cause mortality at 4 weeks. The authors found that 31/71 had delirium. It was not associated with mortality after adjusting for age, sex, and frailty. However after delirium there was a trend to worse cognitive function and significantly worse physical function.
Publication date / reference: 09/07/20 Parauda et al. Posterior reversible encephalopathy syndrome in patients with COVID-19. J Neurol Sci.
Summary: The authors presented clinical and radiographic characteristics of four patients with PRES and PCR-confirmed SARS-CoV-2 infection. All four patients had acute kidney injury with elevated blood pressure preceding the diagnosis of PRES. Neurological findings improved with blood pressure control plus or minus seizure control. All were ultimately discharged to rehabilitation services.
Publication date / reference: 20/06/20 Pilotto et al. The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study. MedRxiv (preprint).
Summary: Multi-centre prospective observational study of cases of encephalitis in SARS-CoV-2 positive patients (n=25). The authors pooled their resources to untease the link between respiratory, inflammatory and putative neurotropic mechanisms in COVID-19. Cases demonstrated wide clinical and radiological heterogeneity. MRI severity seemed to correlate well with response to treatment.
Publication date / reference: 13/06/20 Vespignani et al. Report of EEG Finding on Critically Ill Patients With COVID-19. Ann Neurol.
Summary: This retrospective chart review reports EEG findings from n=26 ICU patients with PCR-positive Sars-CoV-2 and mental state changes. Five patients showed periodic discharges consistent with multiple potential modes of brain injury. The authors call for EEGs to be conducted in COVID-19 patients with mental state changes, but acknowledge that iatrogenic causes (e.g., concomitant medications) may be one explanation for their findings.
Publication date / reference: 12/06/20 Solomon et al. Neuropathological Features of Covid-19. N Eng J Med.
Summary: Correspondence presenting neuropathological findings from autopsies of 18 consecutive patients with fatal SARS-CoV-2 infection. qRT-PCR for Sars-CoV-2 was highly inconsistent, both between patients and between different brain area sections within the same patient. The authors found only hypoxic changes with no evidence of encephalitis or other specific brain changes referable to the virus.
Publication date / reference: 11/06/20 Andriuta et al. COVID-19 Encephalopathy: Detection of Antibodies Against SARS-CoV-2 in CSF. J Neurol
Summary: Letter describing two case studies of patients with PCR-positive Sars-CoV-2 and varying features of encephalopathy. MRI brain showed medial mesencephalic hyperintensity in one patient and bilateral diffuse white matter hyperintensities in the other. CSF samples from both patients were strongly positive for the viral nucleoprotein. The cases illustrate the varied characteristics of SARS-CoV-2 encephalopathy.
Publication date / reference: 10/06/20 Pinto et al. CNS Inflammatory Vasculopathy With Antimyelin Oligodendrocyte Glycoprotein Antibodies in COVID-19. Neurol Neuroimmunol Neuroinflamm.
Summary: Case study of a 44-year-old woman with PCR-positive Sars-CoV-2 and expressive and receptive dysphasia in association with mild right arm and leg weakness, and visual and sensory inattention, subacutely progressing to aphasia and severe weakness. Serial MRI scanning showed progressive T2 hyperintensities. Responded very well to IVMP and plasma exchange. Anti-MOG antibodies returned positive after discharge.
Publication date / reference: 08/06/20 Martin-Jimenez et al. Cognitive impairment is a common comorbidity in COVID-19 deceased patients. A hospital-based retrospective cohort study. MedRxiv.
Summary: Single-centre retrospective cohort study. Perhaps notable for the finding that among n=281 patients with confirmed COVID-19 who subsequently died during March, encephalopathy had been the most common neurological complication – far more common than stroke or seizures. However there was a high rate of dementia in the sample, and those patients were at higher risk of developing encephalopathy (32.1%) than those without pre-existing cognitive impairment (14.7%). Generalisability is hampered by the selected sample and the observation that only one demented patient was admitted to ICU.
Publication date / reference: 06/06/20 Anzalone et al. Multifocal laminar cortical brain lesions: a consistent MRI finding in neuro-COVID-19 patients. J Neurol.
Summary: Case series (n=4) of subacute encephalopathy in SARS-CoV-2 patients. MRI findings demonstrated a subacute reversible cortical picture indicative of vascoconstriction, clearly different from cortical ischemia
Publication date / reference: 02/06/20 Benameur et al. Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease. Emerg Infect Dis.
Summary: Case series (n=3) of SARS-CoV-2 patients who developed encephalopathy and encephalitis. All patients had high CSF levels of anti-S1 IgM and of IL-6, IL-8, and IL-10. One had increased anti–envelope protein IgM. SARS-CoV-2 was not seen in CSF. The authors believe these findings indicate direct invasion of the CNS rather than systemic responses. This paper demonstrates the limitations of attempts to assess complex immune networks in a limited number (n=3) patients, for example both pro (IL-6) and anti (IL-10) inflammatory cytokines correlated together.
Publication date / reference: 01/06/20 Novi et al. Acute disseminated encephalomyelitis after SARS-CoV-2 infection. Neurol Neuroimmunol Neuroinflamm.
Summary: Case report of a patient with visual impairment, sensory deficits and mild behavioural abnormalities. MRI showed spinal lesions with optic nerve enhancement. LP demonstrated a lymphocytic pleocytosis and was positive for SARS-CoV-2 PCR.
Publication date / reference: 30/05/20 Parsons et al. COVID-19-associated Acute Disseminated Encephalomyelitis (ADEM). J Neurol.
Summary: 51-year-old female with SARS-CoV-2 (negative in CSF) developed coma, left hemiparesis and impaired unilateral oculocephalic response. She had multiple acute demyelinating lesions on MRI.
Publication date / reference: 29/05/20 Efe et al. COVID-19-associated Encephalitis Mimicking Glial Tumor: A Case Report. World Neurosurg.
Summary: 35-year-old SARS-CoV-2 positive patient with intractable seizures from a presumed glial cell tumour. However, the resultant cause was a focal area of encephalitis.
Publication date / reference: 28/05/20 Hepburn et al. Acute Symptomatic Seizures in Critically Ill Patients With COVID-19: Is There an Association? Neurocrit Care.
Summary: Case series of two patients who developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures.
Publication date / reference: 27/05/20 Hayashi et al. COVID-19-associated Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion. J Neurol Sci.
Summary: Case report of a 75-year-old with Alzheimer’s Disease who presented with left sided tremor, instability and urinary incontinence. He had no overt respiratory symptoms, but diffusion weighted MRI demonstrated mild encephalitis/encephalopathy with a reversible splenial lesion
Publication date / reference: 27/05/20 Radmanesh et al. COVID-19-associated Delayed Posthypoxic Necrotizing Leukoencephalopathy. J Neurol Sci.
Summary: Case report of a severely ill 50-year-old male with respiratory failure which likely causes depressed consciousness. MRI showed extensive white matter demyelination.
Publication date / reference: 27/05/20 Balestrino et al. Onset of Covid-19 With Impaired Consciousness and Ataxia: A Case Report. J Neurol.
Summary: Case report of a COVID-19 patient presenting with asthenia, gait ataxia, confusion and drowsiness.
Publication date / reference: 27/05/20 Byrnes et al. COVID-19 Encephalopathy Masquerading as Substance Withdrawal. J Med Virol.
Summary: Case report of a patient with encephalopathy and choreiform movements. MRI showed multiple focal enhancing lesions primarily affecting the bilateral medial putamen and left cerebellum along with subcortical lesions suggesting COVID‐19 encephalopathy
Summary: Case report of a patient with seizures and reduced level of consciousness 10 days after the onset of subjective fever, cough, and headache. Nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) was positive, and CT during admission demonstrated diffuse swelling of the brain stem.
Publication date / reference: 26/05/20 Cercy et al. Psychiatric Predictors of COVID-19 Outcomes in a Skilled Nursing Facility Cohort. MedrXiv (preprint)
Summary: After controlling for all medical risk, altered mental status was a predictor of hospital admission, ICU admission, and mortality. Anxiety and dementia were also associated with an elevated risk of death.
Publication date / reference: 23/05/20 Panariello et al. Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: A case report. Brain Behav Immun.
Summary: First reported case of encephalitis associated with SARS-CoV-2 related immunoreactivity. 23-year-old male hospitalized psychotic symptoms: psychomotor agitation, anxiety, thought disorganization, persecutory delusions and auditory hallucinations which appeared over three days. CSF was positive for anti-NMDA receptor antibodies(♦).
Publication date / reference: 22/05/20 Beach et al. Delirium in COVID-19: A Case Series and Exploration of Potential Mechanisms for Central Nervous System Involvement. Gen Hosp Psych.
Summary: Case series (n=4) of patients with SARS-CoV-2 infection where altered mental status was the presenting feature. Uniquely the authors report on alogia, abulia and rigidity in the patients. They discuss possible explanations of such presentations.
Publication date / reference: 21/05/20 Afshar et al. Evolution and resolution of brain involvement associated with SARS- CoV2 infection: A close Clinical – Paraclinical follow up study of a case. MS & Rel Dis.
Summary: Case report of 39-year-old with parainfectious encephalitis with SARS-CoV-2 infection. Despite no comorbidities, this patient had a decline in consciousness and respiratory distress resulting in intubation. Whilst in ICU she experienced a generalised tonic clonic seizure. High FLAIR signals were observed on MRI; however, CSF viral screen and autoimmune serologic markers were absent.
Publication date / reference: 20/05/20 Al-Olama et al. COVID-19-associated Meningoencephalitis Complicated With Intracranial Hemorrhage: A Case Report. Acta Neurochirurgica.
Summary: Case report of a 36-year-old with reduced GCS. Imaging of the brain was consistent with meningoencephalitis alongside discovery of intracerebral and subdural hematomas. SARS-CoV-2 infection was confirmed in PCR analysis of the surgically evacuated intracerebral bleed.
Publication date / reference: 19/05/20 Zayet et al. Encephalopathy in patients with COVID-19: ‘Causality or coincidence?’ Medical Virology.
Summary: Case series (n=2) of patients with confirmed SARS-CoV-2 who presented to healthcare settings with acute confusional state. These patients had normal LP and brain imaging. The authors postulate how varying neurological presentations could be linked to multiple methods of neuroinvasion.
Publication date / reference: 16/05/20 Haddad et al. Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. ID Cases.
Summary: case report of a 41-year-old patient with well-controlled HIV. He presented encephalopathic 6 days after the onset of coryzal symptoms. He developed seizures in hospital, but CSF, EEG and MRI brain were normal. Nasopharyngeal swab was positive for SARS-CoV-2.
Publication date / reference: 15/05/20 Ward et al. Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly. The American Journal of Geriatric Psychiatry.
Summary: Case series of 4 care home residents who developed altered mental state prior to any respiratory symptoms in lab confirmed cases of SARS-CoV-2. The authors state it is crucial that credence is paid to non-respiratory symptoms, specifically neuropsychiatric abnormalities, in formulating a diagnosis of SARS-CoV-2, especially in care home populations to halt the spread of infection(♦).
Publication date / reference: 14/05/20 Deliwala et al. Encephalopathy as the Sentinel Sign of a Cortical Stroke in a Patient Infected With Coronavirus Disease-19 (COVID-19). Cureus.
Summary: Case report of a 31-year-old female with no stroke risk factors who suffered a cortical stroke and tested positive for SARS-CoV-2. The report highlights encephalopathy as a crucial first symptom for a developing stroke. The authors argue for the benefit of routine treatment dose thromboprophylaxis for critically ill patients with SARS-CoV-2 in prothrombotic states.
Publication date / reference: 12/05/20 Norbert et al. Neonatal Early-Onset Infection With SARS-CoV-2 in a Newborn Presenting with Encephalitic Symptoms. Pediatr Infect Dis J.
Summary: Case report of a neonate with confirmed SARS-CoV-2 infection potential acquired through vertical transmission, who developed encephalitic symptoms immediately after birth. The mother described respiratory symptoms and has a persistent fever(♦).
Publication date / reference: 11/05/20 Chaumont et al. Acute meningoencephalitis in a patient with COVID-19. Revue Neurologique..
Summary: Case report of a patient who developed meningoencephalitis one week after the onset of fever and cough. SARS-CoV-2 was diagnosed using a naso-pharyngeal swab.
Publication date / reference: 08/05/20 Alkeridy et al. A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID-19. J Am Geriatr Soc.
Summary: Case report of 73-year-old man presenting with confusion as a first symptom of SARS-CoV-2 infection. The authors do not report CSF sampling.
Publication date / reference: 06/05/20 Huang et al. A Case of COVID-19 Encephalitis. Brain Behav Immun.
Summary: A follow up response from attending infectious disease physicians who cared for a young female with meningoencephalitis without respiratory failure (Duong et al 2020). The infection was confined to the CNS without involving other organ systems. The patient was encephalitic on admission CSF PCR was found to be positive for SARS-CoV-2 infection
Publication date / reference: 05/05/20 Wong et al. Lessons of the month 1: A case of rhombencephalitis as a rare complication of acute COVID-19 infection. Clin Med (Lond)
Summary:Single case report of a 40-year-old man who developed acute brainstem dysfunction 3 days after hospital admission with symptoms of COVID-19. MRI showed changes in keeping with inflammation of the brainstem and the upper cervical cord, leading to a diagnosis of rhombencephalitis. He was managed conservatively with rapid spontaneous improvement in some of his neurological signs.
Publication date / reference: 17/04/20 Neerland et al. COVID-19 in an elderly woman with acute functional decline. Tidsskr Nor Legeforen.
Summary: Single case report of an elderly lady who presented in an acute confusional state secondary to COVID-19. Neuroimaging and CSF are not reported.
Publication date / reference: 17/04/20 Pilotto et al. Steroid-responsive severe encephalopathy in SARS-CoV-2 infection. Preprint (medRxiv)
Summary: Single case report of 60-year old subject with SARS-CoV-2 infection but only mild respiratory abnormalities who developed severe progressive encephalopathy.
Publication date / reference: 16/04/20 Duong et al. Meningoencephalitis without Respiratory Failure in a Young Female Patient with COVID-19 Infection in Downtown Los Angeles, Early April 2020. Brain Behav Immun.
Summary: Single case report of meningoencephalitis. 41-year-old female presented with headache, fever and a new onset seizure associated with covid-19. Authors unable to send CSF for covid-19 analysis.
Publication date / reference: 25/03/20 Moriguchi et al. A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis.
Summary: Single case of Meningitis/Encephalitis presenting with seizure. Nasopharyngeal swab negative for COVID-19 but detected in CSF. MRI demonstrated the abnormal findings of medial temporal lobe including hippocampus suggesting encephalitis.
Publication date / reference: 10/04/20 Ye et al. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun.
Summary: Single case report of a patient who presented meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign) and extensor plantar response were present. The CSF specimen was further tested for SARS-CoV-2 but the result was negative. The patient was treated as encephalitis associated with SARS-CoV-2 infection ‘after careful evaluation by neurological experts’.
Publication date / reference: 06/04/20 Zhou et al. SARS-CoV-2: Underestimated damage to nervous system. Travel Med Infect Dis.
Summary: Single case report of a 56-year-old patient with encephalitis. SARS-CoV-2 was detected in in the cerebrospinal fluid. Almost no additional clinical details.
Publication date / reference: 21/03/20 Bernard-Valnet R et al. Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2. medRxiv (preprint)
Summary: Case series (n=2) of patients that developed meningoencephalitic symptoms with neuropsychological impairment and pathological cerebrospinal fluid features concomitantly to SARS-CoV-2 documented infection. Both patients recovered promptly without treatment.
Publication date / reference: 21/03/20 Filatov A. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus.
Summary: Single case report of a patient who presented with encephalopathy concurrently with COVID-19 infection.
Publication date / reference: 31/03/20 Poyiadji N et al. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy CT and MRI. Radiology.
Delirium and neurocognitive disorders
Publication date / reference: 12/04/2021. Velásquez-Tirado et al. Etiologies of Delirium in Consecutive COVID-19 Inpatients and the Relationship Between Severity of Delirium and COVID-19 in a Prospective Study With Follow-Up. J Neuropsychiatry Clin Neurosci.
Summary: This longitudinal cohort study assessed delirium aetiology, clinical characteristics, and premorbid status of twenty critically ill patients with COVID-19. Five standardised clinical scales were applied in the assessment. The authors found that delirium severity correlated with COVID-19 severity, but not with the pre-existing comorbidities. Fifteen of the twenty patients had hyperactive motor subtype of delirium and all patients had at least three aetiologies. While delirium was more severe in those deceased at the follow-up, the authors conclude that a larger sample size is needed to confirm the association.
Publication date / reference: 29/03/2021 Miskowiak et al. Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables. Eur Neuropsychopharmacol.
Summary: This prospective study follow-up up 29 patients 3-4 months post discharge from hospital with covid-19. Around 60% showed significant abnormalities on cognitive testing. The extent of cognitive impairment was associated with D-dimer during acute illness, but not other markers of severity such as CRP or supplemental oxygen use. There were some associations with cognitive impairment and pulmonary function at follow-up, possibly suggesting a hypoxic element to the impairments, but this small study cannot be conclusive.
Publication date / reference: 8/4/2021. Otto-Watne et al. Delirium is common in patients hospitalized with COVID-19. Intern Emerg Med.
Summary: Otto-Watne and colleagues conducted a cohort study (n = 168) of adult patients admitted to a single centre with confirmed COVID-19. 10% of the cohort presented with delirium upon admission, and 19% developed this during the course of their admission. Delirium was observed in 73% of patients treated in intensive care (n = 30), and all patients who received mechanical ventilation (n = 25). 10 out of the 13 patients that died without receiving mechanical ventilation, developed delirium in the terminal phase of palliative care.
Publication date / reference: 05/03/21 Castro et al. Development and External Validation of a Delirium Prediction Model for Hospitalized Patients With Coronavirus Disease 2019. J Acad Consult Liaison Psychiatry.
Summary: Castro et al describe the development of an incident delirium predictive model for COVID-19 patients. Supervised machine learning was applied to electronic health records data of a “training” cohort of 2152 patients. This was then validated in 3 different hospitals, in a second testing group of 755. Of these 2907 COVID-19 patients, 488 (16.8%) developed delirium. The concordance index (c-index) in the validation cohort was 0.75 (0.71-0.79) and the lift in the top quintile was 2.1. At a sensitivity of 80%, the specificity was 56%, negative predictive value 92%, and positive predictive value 30%. Equivalent model performance was observed in subsamples stratified by age, sex, race, need for critical care and care at community vs. academic hospitals. The authors highlighted the importance of scalable and generalisable EHR-based predictive models in the contactless evaluation of patients.
Publication date / reference: 13/02/2021 Ferrucci et al. Long-Lasting Cognitive Abnormalities after COVID-19 Brain Sci.
Summary: The authors aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge. We recruited 38 (aged 22–74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in non intensive COVID units. Participants underwent neuropsychological testing about 5 months after hospital discharge. 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits. Twenty-one percent presented with deficits in both processing speed and verbal memory.
Publication date / reference: 15/02/21. Amalkanti et al. Cognitive assessment in asymptomatic COVID-19 subjects. Virusdisease.
Summary: The authors compared the cognitive assessment scores of 93 asymptomatic COVID-19 subjects with those of 102 controls. Using the MoCA, COVID-19 patients secured marginally lower scores than controls in the domains of visuoperception, naming and fluency. The study is limited by ‘hospital bias’; in addition, all of the people in the study had < 4 years of education.
Publication date / reference: 15/02/2021 Jaywant et al. Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19. Neuropsychopharmacology.
Summary: In this study, the authors analyzed cross-sectional scores from the Brief Memory and Executive Test (BMET) in a cohort of N = 57 COVID-19 patients undergoing inpatient rehabilitation, calculating the frequency of impairment based on neuropsychologist diagnosis and by age-normed BMET subtests. They evaluated the frequency, severity, and profile of cognitive dysfunction in patients recovering from prolonged COVID-19 hospitalization who required acute inpatient rehabilitation prior to discharge. Forty-six patients (81%) had cognitive impairment, ranging from mild to severe. Deficits were common in working memory (26/47 [55%] of patients), set-shifting (21/44 [47%]), divided attention (18/39 [46%]), and processing speed (14/35 [40%]).
Publication date / reference: 09/02/2021 Wang et al. COVID-19 and dementia: Analyses of risk, disparity, and outcomes from electronic health records in the US. Alzheimers Dement.
Summary: This retrospective case-control study aimed to analyse patient electronic health records of (n=61.9 million) patients aged ≥ 18 years in the United States up to August 2020. The author found that patients with dementia were at increased risk for COVID-19 compared to patients without dementia (adjusted OR [AOR]=2), with the strongest effect for vascular dementia (AOR=3.17), followed by presenile dementia (AOR=2.62), Alzheimer’s disease (AOR=1.86), senile dementia (AOR=1.99) and post-traumatic dementia (AOR=1.67). A racial disparity was also detected, where patients of colour with dementia had a higher risk of contracting COVID-19 compared to caucasian patients. The 6-month mortality and hospitalization risks in patients with dementia and COVID-19 were 20.99% and 59.26%, respectively. They concluded that these findings highlight the need to protect patients with dementia as part of the strategy to control the COVID-19 pandemic.
Publication date / reference: 08/02/2021 Alemanno et al. COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience. PLoS One.
Summary: This cross-sectional study analysed the neurocognitive and neuropsychiatric status of 87 patients who had been stepped down to covid-19 rehab. In total, 80% had deficits on cognitive scales (MoCA and MMSE) and 40% had concurrent mild/moderate depression. Worsening cognitive deficit was associated with age, but not type of ventilatory support in the acute phase (a correlate of severity).
Publication date / reference: 10/02/2021 Kenerly et al. Altered mental status is an independent predictor of mortality in hospitalized COVID-19 patients. Ir J Med Sci.
Summary: In this retrospective case notes review, Kenerly and colleagues investigated the outcomes of patients with PCR confirmed SARS-Cov-2 infection who presented with altered mental status (AMS). Data was extracted from the electronic medical records of 710 patients, 73 of whom presented with AMS. The authors elicited that patients presenting with AMS were more likely to be ≥ 70 and have CKD, cerebrovascular disease or dementia, and were less likely to present with typical COVID-19 symptoms. AMS was associated with higher rates of mortality, ICU admission, requirement for mechanical ventilation, and increased length of hospital stay.
Publication date / reference: 08/01/2021. Brenda T Pun et al. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study Lancet Respiratory Medicine.
Summary: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries and included all patients (aged ≥18 years) admitted to participating ICUs with SARS CoV-2 infection before April 28, 2020. Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day, whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium.
Publication date / reference: 27/11/2020 Rebora et al. Delirium in Patients with SARS-CoV-2 Infection: A Multicenter Study. J Am Geriatr Soc.
Summary: In this observational multicenter study, conducted in four hospitals in Italy between February and May 2020, Rebora et al. explored the prevalence of delirium in 516 hospitalised patients with COVID-19 and the factors associated with it. The authors reported that on admission, 73 patients (14.1%) had delirium, diagnosed by either standardised criteria or clinical impression, depending on the site. Delirium was associated with higher age, higher number of pre-existing diseases (OR = 1.20, 95% CI = 1.03; 1.40), higher prevalence rates of dementia (OR = 4.66, 95% CI = 2.03–10.69), chest X‐ray or CT opacities (OR = 3.29, 95%CI = 1.12–9.64 and OR = 3.35, 95%CI = 1.07–10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). Malnutrition and higher dependency in activities of daily living (ADL) before admission were also related to higher delirium prevalence in COVID-19 hospitalised patients.
Publication date / reference: 01/12/20. Mattace-Raso et al. Delirium: A Frequent Manifestation in COVID-19 Older Patients. Clin Interv Aging.
Summary: The authors conducted a retrospective chart review to assess the prevalence of delirium in patients admitted to a COVID-19 ward. During the period March-April 2020, 47 patients (out of 123, 38%) had signs/symptoms of delirium, the majority of whom (n=39) developed a delirium during admission to the intensive care unit. The mean age of patients with delirium was 71.3 years, but the overall mean age of patients admitted to the COVID-19 ward was not given. The authors refer to the use of DSM-5 delirium criteria when patients who were admitted to ICU were assessed for delirium, but it is unclear if such robust screening measures were used generally for patients on the COVID-19 ward. Prospective, longitudinal studies are required to elucidate the prevalence and outcome of patients with COVID-19 delirium.
Publication date / reference: 25/11/2020 Khan et al. Delirium Incidence, Duration, and Severity in Critically Ill Patients With Coronavirus Disease 2019. Crit Care Explor.
Summary: This retrospective cohort study aimed to assess the incidence, duration and severity of delirium among patients admitted to the ICU with COVID-19. They assessed 268 patients with a mean age of 58.4. They found that the first Confusion Assessment Method for the ICU (CAM-ICU) was positive for delirium in 61.9% of patients with hypoactive delirium the most common subtype (87.4%). At day 14, the median number of delirium free days was 5 and the median CAM-ICU was 6.5 indicating a severe category. Mechanical ventilation was associated with greater odds of developing delirium even adjusting for sedating medication.
Publication date / reference: 12/11/20 Rozzini et al. Delirium: clinical presentation and outcomes in older COVID-19 patients. Front Psychiatry
Summary: The authors of this study report clinical features and outcomes in 14 older patients with COVID-19 on a non-ICU ward. Hypokinetic delirium and hyperkinetic delirium were observed in 6/14 and 8/14 patients respectively, and overall mortality rate was 10/14. The authors also note that two survivors had dementia but did not display features of acute respiratory distress syndrome, whilst the other two did demonstrate respiratory distress syndrome but not dementia.
Publication date / reference: 11/11/2020. Kennedy et al. Delirium in Older Patients With COVID-19 Presenting to the Emergency Department. Jama Netw Open.
Summary: Kennedy et al. reported the findings of a multi-center cohort study in the US. A total of 817 older patients (>65 years old) with COVID-19 presenting to the emergency department were recruited to the study. 28% of which (N=228) had delirium at presentation, among those, 13% (N=37) had delirium as their primary presenting symptom and 37% (N=84) did not present with typical sign/symptoms associated with COVID-19 (fever or shortness of breath). Delirium at presentation was significantly associated with poor outcomes, including ICU stay, needing further rehabilitation facility and death. Previous diagnosis of neuropsychiatric conditions, visual or hearing impairment, older age, assisted living residence were all associated with an increased risk of delirium. Delirium were found to be the sixth most common presenting symptoms in this cohort of patients. The authors highlighted several limitations of the study in their article, one important to note is that the prevalence of delirium is likely to have been underestimated as delirium is not part of routine screening in the ED department and diagnosis was estimated from clinical notes. This study further highlights that delirium can present as a main symptom or in some cases the sole symptom of COVID-19 in older populations. Early identification and management is crucial in this cohort of patients given the associated poorer outcome.
Publication date/ reference: 01/05/2021 Mattioli et al. Neurological and cognitive sequelae of Covid-19: a four month follow-up. J Neurol.
Summary: In this study, 120 healthcare workers who had suffered with mild covid-19 were followed-up with neurological and cognitive examinations at four-months and compared to a matched control group. Reassuringly, none had any neurological deficits which could be attributed to covid-19, and there were no differences between MMSE scores. Despite this, scores on mental health outcomes were worse in the covid-19 group, and many patients had ongoing symptoms such as anosmia and fatigue.
Publication date/ reference: 29/04/2021 Tran et al. Development and validation of the long covid symptom and impact tools, a set of patient-reported instruments constructed from patients’ lived experience. Clin Infec Dis.
Summary: This manuscript presents the results of two phases of research into patients’ own perceptions of their long covid illnesses. In the first stage, 492 patients answered open-ended questions about their illnesses, and the authors performed qualitative analysis on the answers. From this, they developed a long covid ‘symptom and impact’ scale, which was validated on a second group of long covid patients (of note, half of this second cohort was constituted by patients who had answered the questions in the first stage). The second group (n = 1022) reported a number of symptoms, including The symptoms most frequently reported were fatigue (n=899), headaches (n=709), difficulties concentrating/mental fog (n=650), sleep disorders (n=603), and dyspnea (n=570).
Publication date / reference: 26/04/2021 Wong and Weitzer. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas).
Summary: Wong and Weitzer conducted a systematic review of long-COVID symptomatology. 21 studies were included in a qualitative analysis. The authors then compared the reported long-COVID symptoms to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms compiled from multiple case definitions and found that 25/29 known ME/CFS symptoms were reported by at least one selected long COVID study. All three major criteria of ME/CFS, namely fatigue, reduced daily activity, and post-exertional malaise, were reported by multiple long-COVID studies. The authors suggest that there is a large overlap between ME/CFS and long-COVID symptoms, and call for the monitoring and treatment of patients with long-COVID.
Summary: Goodman et al present a case series of 6 patients with COVID-19 with dysautonomia. For 5 of these patients, autonomic dysfunction was a presenting symptom of COVID-19. 1 other patient developed symptoms 6 weeks following the initial COVID-19 infection. The results of autonomic testing were varied, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.
Publication date / reference: 31/03/21. Khademi et al. Prevalence of Mental Health Problems and Its Associated Factors Among Recovered COVID-19 Patients During the Pandemic: A Single-Center Study. Front Psychiatry.
Summary: The authors of this prospective cross-sectional study surveyed symptoms of depression and anxiety (using the PHQ-4) and post-traumatic stress (using the PCL-5) in 602 patients who had recovered from COVID-19. They found prevalence rates of around 5% for anxiety and depressive symptoms, and 3.8% for PTS symptoms. There was little evidence of difference in prevalence between hospitalised and non-hospitalised cases.
Publication date / reference: 19/04/2021 Jain, Harmon and Sonagere., Functional Outcomes and Post‐Discharge Care Sought by Patients with COVID‐19 Compared to Matched Controls After Completing Inpatient Acute Rehabilitation. PM&R.
Summary: The objective of this study was to determine the functional outcomes and utilization of follow up medical care ninety days following discharge from acute inpatient rehabilitation, as compared to rehabilitation impairment and age matched controls. This was a prospective, single‐center cohort study The COVID‐19 patient group had similar improvements in functional outcomes as compared to controls. Patients with COVID‐19 required fewer readmissions than their matched controls in the 30‐90‐day periods and required fewer follow up visits with specialists after discharge from the IRF.
Publication date / reference: 13/04/2021 Prileau. Learning from the Experiences of COVID-19 Survivors: A Descriptive Study. JMIR Form Res.
Summary: In this study, 54 participants completed a survey on the effects of covid-19. Over 70% reported experiencing symptoms lasting longer than the commonly cited 2-weeks, even for mild cases. Mean recovery time was five weeks, and 56% still experienced lingering symptoms of COVID-19 after two months.
Publication date / reference: 20/01/2021 Iwu, Iwu and Wiysonge The occurrence of long COVID: a rapid review. Pan Afr Med J.
Summary: This rapid review was aimed at synthesizing evidence on the long-term effects of the SARS-CoV-2 infection among survivors. Authors considered both randomised controlled trials and non-randomised studies eligible for inclusion in this review. The following databases were searched: PubMed, Scopus, Cochrane library, Google Scholar, and the World Health Organization (WHO) COVID-19 database. The reference lists of all the included studies were also searched. The majority of symptoms reported were fatigue, shortness of breath, cough, and sleep disorders. Mental conditions, such as depression and anxiety disorders, were also reported. In conclusion, this study showed that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness.
Publication date/ reference: 19/04/2021 Jain E, Harmon EY, Sonagere MB. Functional Outcomes and Post-Discharge Care Sought by Patients with COVID-19 Compared to Matched Controls After Completing Inpatient Acute Rehabilitation. PM R.
Summary: The authors of this review analysed the outcomes of rehabilitation and follow up medical care of patients with COVID-19 ninety days post-discharge from acute inpatient medical care. A survey questionnaire was completed by a total of 36 patients recovering from COVID-19 infection and a control age and impairment group of 64 persons. The rehabilitation of functional outcomes were similar in both COVID-19 patients and the control group. Fewer re-admissions and follow-up visits with specialists were required by COVID-19 patients in the 30-90-day period, compared to the subjects in the control group.
Publication date / reference: 08/04/2021 Gaber et al., Persistent post-covid symptoms in healthcare workers Occup Med (Lond)
Summary: This retrospective multi-centre (single hospital Trust) study investigated general incidence of COVID-19 amongst HCW employees in June 2020. They noted an incidence amongst staff of 932 of 3759 staff (24%). Questionnaires were then sent to staff concerning persistent symptoms 4 months after a positive test (n=138). Overall, 45% reported persistent symptoms and more specifically: 54 (39%) reported fatigue, 49% reported sleep disturbance and 44 reported mood disturbance. The authors found that the majority of staff with persistent symptoms were reluctant to seek support and suggest increased awareness for occupational health services.
Publication date / reference: 31/03/2021. Blazhenets et al. Slow but evident recovery from neocortical dysfunction and cognitive impairment in a series of chronic COVID-19 patients. J Nucl Med.
Summary: This longitudinal, single-centre study of eight subjects compared 18F-FDG PET scans and Montreal Cognitive Assessments (MoCA) undertaken in the subacute phase of COVID-19 with those repeated at six months. The COVID-19-related cortical hypometabolism pattern on 18F-FDG PET correlated inversely with MoCA scores and did not resolve completely in all patients at the follow-up. The authors conclude that whilst cognitive recovery occurs, residual impairment is still detected at six months, providing insights into the long-term effects of COVID-19.
Publication date / reference: 13/03/2021 Versace et al. Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19. Clin Neurophysiol.
Summary: The authors of this study included twelve patients who had recovered from COVID-19 pneumonia, with persistent neurological complications and physical and mental fatigue. Participants underwent psychometric evaluation and intracortical activity was assessed through transcranial magnetic stimulation. Patients reported considerable fatigue (Fatigue Rating Scale score 8.1 ± 1.7) and had pathological scores in the Frontal Assessment Battery (12.2 ± 0.7). TMS demonstrated marked reduction of short-interval intracortical inhibition and disruption of long-interval intracortical inhibition compared to ten healthy controls.
Summary: This prospective study multi-centre cohort study investigated neurological disorders in COVID-19 patients within 3 months of onset (n=90). The cohort was relatively young (median age 38) and the majority were males (98.9%). Key neurological disorders seen ranged from CNS, CVT, Stroke, Intracerebral haemorrhage, PNS symptoms and included: 19 patients had acute ischaemic stroke/TIA, 7 patients developed neuropathy, 4 patients developed severe encephalitis and 4 patients developed Cerebral venous thrombosis. Overall, 39 patients had a wide spectrum of neurological complications (0.08%) with variable courses.
Publication date / reference: 12/03/2021 Avenali et al., Clinical and Electrophysiological Outcome Measures of Patients With Post-Infectious Neurological Syndromes Related to COVID-19 Treated With Intensive Neurorehabilitation. Front Neurol.
Summary: This study investigated (n=5) hospitalised COVID-19 patients and PNS who were followed up after 6 months. All patients underwent intensive rehabilitation. 3 (60%) had polyradiculoneuropathy and in these patients they had acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor and sensory axonal neuropathy (AMSAN) which were stable in the majority of patients at baseline. 2 (40%) of patients had myelitis at baseline which had variable recovery at the follow-up. Though this is a small sample, it is interesting to see the relation to electrophysiological findings and the significance of neurological rehabilitation.
Publication date / reference: 25/03/21. Osikomaiya et al. ‘Long COVID’: persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria. BMC Infect Dis.
Summary: This study retrospectively examined discharged COVID-19 patients. The authors found that 40.9% of patients had persistent COVID-19 symptoms following discharge with 19.7% experiencing more than three symptoms. Most commonly found were easy fatigability (12.8%), headaches (12.8%) and chest pain (9.8%). They also found that those with symptomatic moderate COVID-19 disease were more likely to suffer long-covid symptoms than those with mild disease post discharge. The authors urged careful monitoring of those discharged following COVID-19 in order to mitigate symptom-effect and quality of lie.
Publication date / reference: 23/03/2021. Graham et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 “long haulers”. Ann Clin Transl Neurol.
Summary: This prospective study by Graham et al. aimed to characterise the neurologic manifestations of Covid-19 “long haulers” who were not hospitalised. Data from 100 patients who presented to the Neuro-Covid-19 clinic was recorded. The authors looked at frequency of neurologic symptoms and used patient reported QOL measures as well as cognitive assessments as outcome measures. The authors identified that the main neurologic manifestations was “brain fog” where approximately 81% of patients reported this. Other common symptoms included headache, numbness/tingling, dysgeusia, anosmia, and myalgia. The authors also recognised that the SARS-CoV positive patients performed worse in cognitive tasks compared to their demographic matched control. Overall, the conclusion was that patients who were “long haulers” and non-hospitalised with COVID-19 experienced persistent brain fog and fatigue which had an impact on their QOL and cognition.
Publication date / reference: 16/03/21 Martillo et al. Postintensive Care Syndrome in Survivors of Critical Illness Related to Coronavirus Disease 2019: Cohort Study From a New York City Critical Care Recovery Clinic. Crit Care Med.
Summary: The authors aimed to describe the physical, psychiatric, and cognitive impairments of 45 COVID-19 ICU survivors. They recruited 45 patients who had survived a minimum 7-day ICU length of stay and who were referred to a critical care recovery clinic. One month post-hospital discharge, 8/45 patients scored >9 on the PHQ-9, potentially indicative of at least moderate depressive symptoms. Insomnia was a common concern with 17/45 patients scoring at least subthreshold in severity. Among 30 patients who received the MoCA, 6/30 scored <19 (only one of whom had a pre-existing dementia diagnosis).
Publication date / reference: 5/3/2021. Zhou et al. Does Post-COVID-19 symptoms exist? A longitudinal study of COVID-19 sequelae in Wenzhou, China. Ann Med Psychol (Paris).
Summary: Zhou and colleagues followed up 89 patients who were discharged from hospital following admission for COVID-19, each for at least 3 weeks. Participants completed semi-structured questionnaires regarding long-term symptoms and general health status. The most frequently reported symptoms were cough (46.1%) and fatigue (36.0%). Two patients reported myalgia. 73 patients were assessed with the PTSD checklist-civilian version (PCL-D). 11% of survivors were determined to have probably PTSD and 13.7% were determined to have PTSD, according to the checklist.
Publication date / reference: 10/03/2021 Sigfrid et al. What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19? A harmonised, global longitudinal observational study protocol. BMJ Open.
Summary: This protocol outlines an international, multi-site, prospective longitudinal study linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO’s Clinical Characterisation Protocol. Their aim is to analyse patients with confirmed COVID-19 over a period of time in order to better understand the long term impact on their physical and psychosocial health. They hope by doing this it can then inform strategies to understand and manage long term sequelae of COVID-19 to improve morbidity.
Publication date / reference: 07/03/21. Sollini et al. Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study. Eur J Nucl Med Mol Imaging.
Summary: In this mechanistic study, the authors compared whole-body [18F]FDG-PET/CT findings from a group of patients with long-COVID (n=13, defined as at least one persistent symptom for >30 days after infection recovery) to a group of 26 melanoma patients with negative PET/CT (age and sex-matched). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). It is worth noting that these results have not been corrected for multiple statistical testing which increases the risk of a type one error.
Publication date / reference: 05/3/21. Zhou et al. Does Post-COVID-19 symptoms exist? A longitudinal study of COVID-19 sequelae in Wenzhou, China. Ann Med Psychol (Paris).
Summary: This study aimed to examine patient’s outcomes following discharge after being hospitalised with COVID-19. 89 patients out of 14,139 confirmed SARS-CoV-2 infected patients were followed up at least three weeks after discharge with a structured questionnaire on post infective symptoms and health status. 6.7% had recurrence of positive RNA at the three week follow up. Most frequently reported symptoms included cough (46.1%), fatigue (36.0%) and 2.2% complained of myalgia and arthralgia. 42.7% of the patients felt completely back to baseline, whilst 47.2% felt much improved and one felt no better and one felt worse. 11% tested positive for PTSD. The authors concluded that long-term psychological support might be a crucial element in aiding reduced morbidity associated with COVID-19.
Publication date / reference: 10/02/2021 Humphreys et al. Long COVID and the role of physical activity: a qualitative study. BMJ Open.
Summary: Semi-structured telephone interviews of 18 individuals with long COVID were conducted. Four main themes were identified: struggling with reduced physical function, challenges of finding and interpreting advice on physical activity, individual approaches to symptom management, conflict with self-concept of function and fear of permanent reduction in physical and cognitive function.
Publication date / reference: 09/03/2021 Leite et al. Persistent symptoms and disability after COVID-19 hospitalization: data from a comprehensive telerehabilitation program. Arch Phys Med Rehabil.
In this study of 1.696 patients requiring hospitalisation for COVID-19, the authors highlight high levels of disability, dyspnea, dysphagia. These patients, with a mean age of 72 years old also required significant assistance with their ADLs following discharge. Unsurprisingly, those admitted to ICU presented more advanced disability parameters.
Publication date / reference: 11/2020 Moradian et al. Delayed Symptoms in Patients Recovered from COVID-19. Iran j Public Health.
Summary: This is a follow-up study of 200 patients with moderate to severe COVID-19, 6 weeks after discharge, conducted in a referral general hospital in Tehran, India, looking into the prevalence of delayed symptoms. Fatigue (39 patients, 19.5%) , dyspnea (37 patients, 18.5%), weakness (36 patients, 18%) and anxiety (30 patients, 15%) were reported as the most common symptoms within this sample 6 weeks after discharge.
Publication date / reference: 02/03/21. Monti et al. Two months quality of life of COVID-19 invasively ventilated survivors; an Italian single-center study. Acta Anaesthesiol Scand.
Summary: The authors reported the quality of life of 39 invasively ventilated ARDS COVID-19 survivors, post-hospital discharge. The majority of patients reported no cognitive decline, no limitation in daily activities and no clinically significant psychological impairment or PTSD. Eight patients reported moderate anxiety or depression.
Publication date/reference: 25/02/2021 Townsend et al., Fatigue following COVID-19 infection is not associated with autonomic dysfunction. PLoS One.
Summary: This was a case-control study, investigating whether the common long-term symptom of fatigue is associated with persistent autonomic dysfunction in COVID-19 patients. Fatigued and non-fatigued (n=20 in each arm) post-COVID patients were recruited and then assessed for fatigue and autonomic function using validated tests. No pathological differences were found between fatigued and non-fatigued patients on autonomic testing and monitoring. Fatigue was found to be associated with increased anxiety.
Publication date / reference: 12/02/2021. Wu et al. Health-related quality of life of hospitalized COVID-19 survivors: An initial exploration in Nanning city, China. Soc Sci Med.
Summary: This is a qualitative study which evaluated the holistic experience of 16 patients 3 months after discharge from COVID-19. In terms of mental health problems, anxiety was the most frequently reported symptom. Additionally, stigma from having contracted SARS-CoV-2 had a significant effect on survivors’ quality of life. Traumatic experiences and loneliness were also reported in a minority of participants.
Publication date / reference: 2/2/21 Barin et al. Joint investigation of a 2-month post-diagnosis IgG antibody levels and psychological measures for assessing longer term multi-faceted recovery among COVID-19 cases in Northern Cyprus. Front Public Health.
Summary: This prospective study (n=74) used questionnaire-based surveys to investigate the negative psychological impact of COVID-19 infection alongside IgG titers. Psychological burden and IgG levels were greater amongst those with comorbidities and more critical illness. The authors conclude that greater awareness of the psychological impact of COVID-19 illness in this group would be beneficial at this stage in the pandemic.
Publication date / reference: 01/12/20 Suárez-Robles et al. Ninety days post-hospitalization evaluation of residual COVID-19 symptoms through a phone call check list. Pan Afr Med J.
Summary: This is an observational study of symptoms experienced by patients with COVID-19 (n=134) after 90 days post-discharge from hospital in Spain. This was evaluated via structured interviews which included a checklist of symptoms. The authors found that the most frequent symptoms were fatigue (73/134, 54.5%), dyspnoea (54/134, 40.3%) and weight loss (50/134, 37.7%). The most common psychological symptom was anxiety (76/134, 56.7%), as evaluated via the GAD-7 scale.
Publication date / reference: 01/12/20 de Graaf et al. Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach. EClinicalMedicine.
Summary: The authors present a multidisciplinary evaluation of COVID-19 patients 6 weeks following discharge. Around 40% of the cohort had been treated in ITU. Most patients suffered from functional limitations, with dyspnea on exertion most frequently reported. Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients.
Publication date / reference: 07/02/2021. Jacobson et al. Patients with uncomplicated COVID-19 have long-term persistent symptoms and functional impairment similar to patients with severe COVID-19: a cautionary tale during a global pandemic. Clin Infect Dis.
Summary: in this brief report, researchers from Stanford university surveyed 118 (22 hospitalised; 96 non hospitalised) individuals with confirmed COVID-19 3-4 months after their initial diagnosis. They found that persistent symptoms and functional impairment had similar levels of prevalence in hospitalized and non hospitalized patients. Whilst the study is limited by the small sample size, risk of recall bias and lacks generalisability, the finding is consistent with larger research findings elsewhere and continues to highlight significant potential of ongoing functional impairment and morbidity in both hospitalised but more strikingly non-hospitalised patients.
Publication date / reference: 24/2/21 Gennaro et al. Persistent psychopathology and neurocognitive impairment in COVD-19 survivors: effect of inflammatory biomarkers at three-month follow-up. Brain Behav Immun.
Summary: In a prospective study, Gennaro et al. aimed to identify a relationship between systemic inflammation during acute COVID-19 infection and subsequent psychopathology at 3 months post-discharge (n=226). 35.8% (n=-81) patients self-reported clinically significant symptoms meeting at least 1 psychopathological dimension at 3 months. Additionally, 24.3% (n=55) met DSM-5 criteria for at least 1 major psychiatric disorder according to psychiatric assessment at 3 months. Female gender (F=11.12; p=0.001), prior psychiatric diagnosis (F=10.65, p=0.001) and presence of psychopathology at 1 month follow-up (F=15.16; p<0.001) all significantly predicted the continuing presence of psychopathology at 3 months. Systemic inflammation (SI) during acute illness also predicted the severity of depressive psychopathology at 3 months (p<0.001). Change in SI from 1 to 3 months follow-up predicted severity of depression (Wald W2=14.304, p=0.0002). Gennaro and colleagues hypothesise that systemic inflammation during COVID-19 illness predisposes to later psychopathology in survivors.
Publication date / reference: 03/2021 Soldati et al. Telephone Screening of Cognitive Status (TICS) in severe COVID-19 patients: Utility in the era of social isolation. eNeurologicalSci.
Summary: This pilot study aimed to assess the feasibility and practical application of a remote cognitive and quality of life assessment tool. They used the Telephone Screening of Cognitive Status (TCIS) on patients who had been discharged from ICU with severe COVID-19. 23 individuals were included in the full follow up. The median interval between discharge and first contact was 83 days, and between first contact and TCIS 15 days. Mild cognitive impairment was diagnosed in three patients with 14/23 displaying normal results (six inconclusive). They found the TCIS is a promising tool for remote assessment.
Publication date / reference: 02/01/21 Pilotto et al. COVID-19 severity impacts on long-term neurological manifestation after hospitalisation. BioRxiv (pre-print, not peer-reviewed)
Summary: The authors of this prospective observational study evaluated the presence of sequelae in previously hospitalised patients with COVID-19 who were assessed 6 months after discharge (n=165). Concordant with other reports of persistent COVID-19 symptoms, neuropsychiatric sequelae were common. Fatigue (34%), memory/attention (31%), and sleep disorders (30%) were the most frequently recorded symptoms. On neurological examination abnormalities were detected in 37.4% of patients, the most common of which included cognitive deficits (17.5%), hyposmia (15.7%) and postural tremor (13.8%). Subgroup analysis of patients with demonstrable cognitive deficits compared to patients without showed that age, sex and pre-admission comorbidities were similar, however, the group with cognitive deficits had more severe COVID-19 disease during admission and long duration of inpatient stay.
Publication date / reference: 16/02/2021 Klein et al. Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infections. A cohort study in Israeli patients. Clin Microbiol Infect.
Summary: The authors of this cohort study examined 103 Israeli residents who were over the age of 18, had positive confirmation of SARS-CoV-2 by RT-PCR, and non-severe symptoms. They conducted phone interviews over a six month period assessing symptom onset, duration, severity and resolution. 45/103, 42/103, 40/103 or 39/103 of the patients experienced headache, fever, muscle ache, or dry cough as the first symptom respectively. Fever had the shortest duration and smell and taste symptoms persisted the longest. Smell and taste symptom resolution correlated with severity of change. AT six months, 47/103 patients still had one unresolved symptom: 23/103 with fatigue; 15/103 with dysosmia; 8/103 with dysgeusia, and 8/103 with breathing difficulties.
Publication date/reference: 11/02/2021 Sykes et al., Post-COVID-19 Symptom Burden: What is Long-COVID and How Should We Manage It? Lung.
Summary: This study sought to understand the symptom burden of Long-COVID in a cohort of COVID-19 patients (n=387) discharged from a UK university teaching hospital following treatment for COVID-19 pneumonia. Primary findings included the presence of long-lasting symptoms being a common phenomena, and biopsychosocial factors playing a greater role in the aetiology of LONG-covid than the direct effect of SARS-CoV-2.
Publication date / reference: 05/02/2021 Islam et al. Treatment, Persistent Symptoms, and Depression in People Infected with COVID-19 in Bangladesh. Int J Environ Res Public Health.
Summary: This cross-sectional study based in Pakistan assessed 1002 patients one month after their COVID-19 diagnosis. An online questionnaire assessing socio-demographics, lifestyle, COVID-19 symptoms, medication and depression. 20% of participants reported ongoing COVID-19 symptoms, the most common being diarrhoea and fatigue. 48% of participants were categorised as having moderate to severe depression. Depression during COVID-19 had a positive correlation with lower family income, poorer health status, sleep disturbance, hypertension, lack of physical activity, respiratory symptoms and persistent COVID-19 symptoms.
Publication date / reference: 19/11/20. Doykov et al. ‘The long tail of Covid-19’ – The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients. F1000Res.
Summary: This pilot study used a custom targeted mass spectrometry based assay panel that looks at up to 96 pro- and anti-inflammatory associated proteins. This assay was used to compare 10 COVID positive and 10 COVID negative samples from healthcare workers at least 40-45 days post infection. The authors found a clear separation of the positive and negative samples indicating the serum immune profile from people infected with SARS-CoV-2 is still significantly affected even 40 days post-infection- in particular six proteins were significantly altered, most of which were antiinflammatory or associated with the stress response. The authors argue that this may indicate that long Covid symptoms could be related to a lingering ‘tail’ and an abnormal inflammatory response to an infection, providing possible targets for drug therapy for “long-covid”
Publication date / reference: 20/12/20. Ladds et al. Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services. BMC Health Serv Res.
Summary: In this qualitative study of 114 participants from long-COVID patient support groups, through 55 individual interviews and eight focus groups, 32 were doctors and 19 other healthcare professionals. 31 had attended hospital, of whom eight had been admitted. Participants felt the illness was confusing with varied, relapsing-remitting symptoms and uncertain prognosis, with a sense of stigma, difficulty accessing services and achieving a diagnosis.
Publication date / reference: 14/01/21. Weerahandi et al. Post-Discharge Health Status and Symptoms in Patients with Severe COVID-19. J Gen Intern Med.
Summary: This prospective single health system observational cohort study aimed to characterize overall health, physical health, and mental health of patients 1 month after discharge for severe COVID-19. The authors enrolled (n=161) patients ≥ 18 years hospitalized with COVID-19 disease who required at least 6 L of oxygen, had intact baseline cognitive and functional status, and were discharged alive at between 30 and 40 days after discharge. They found that 74% reported shortness of breath within the prior week, rated their physical health and mental health as worse in their post-COVID state compared to their pre-COVID state; 35.1% without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 13.5% still using oxygen at time of survey. They concluded that patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health, and mental health for at least several weeks after hospital discharge.
Publication date / reference: 23/11/2020. Woo et al. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun.
Summary: In this cross-sectional study the authors recruited 18 mostly young patients 20-105 days (median, 85 days) after recovery from mild to moderate disease who visited the outpatient clinic for post-COVID-19 care. Fourteen of these patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. Short-term memory, attention and concentration were particularly affected by COVID-19. In this very small sample, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation.
Publication date / reference: 13/01/2021. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up. J Neurology.
Summary: This prospective consecutive observational study aimed to systematically describe the Central and Peripheral Nervous System complications in patients with a confirmed diagnosis of COVID-19. A total of 41 CNS/PNS complications were identified in 28 of 61 patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Other CNS complications included ischemic stroke, acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy with prolonged ICU stay as an independent predictor.
Publication date / reference. 26/12/2020. Taboada et al. Post-COVID-19 functional status six-months after hospitalization. J Infect.
Summary: In this letter to the editor in response to Garringue et al.study published in August 2020 in the journal, the authors present findings from their own cross-sectional study investigating the functional status of COVID-19 patients 6 months after hospitalisation (N=183). The authors found a large proportion of patients (47.5%) reported reduced functional status following discharge from hospital 6 months on.
Publication date / reference: 30/11/2020. van der Sar-van der Brugge et al. Pulmonary function and health-related quality of life after COVID-19 pneumonia. Respir Med.
Summary: This is a prospective longitudinal cohort study examining the effects of COVID-19 on patients’ pulmonary function and quality of life at 6 weeks post-discharge. Among 101 patients, the authors found that Hospital Anxiety and Depression Scale (HADS) scores ≥8 (indicating borderline abnormal) for depression were found in 16.6% and in 12.5% for anxiety. Significant impairment was found across all Health-Related Quality of Life (HRQoL) Short-Form 36 (SF-36) domains, except bodily pain. SF-36 was also shown to have significant positive correlations with measures of lung diffusion capacity. The authors conclude that in view of this correlation, follow up for COVID-19 patients should include pulmonary function tests alongside measures of quality of life.
Publication date / reference: 29/11/2020 Walsh-Messinger et al. The kids are not alright: a preliminary report of post-COVID syndrome in university students. medRxiv.
Summary: This retrospective cohort study aimed to compare the disease severity between undergraduates with post COVID-19 syndrome (symptoms ≥28 days) (n=22) and their fully recovered peers (n=21). Using self-report questionnaires they found that students with post COVID 19 syndrome had higher depression severity scores (p=.04), were more likely to be female (21/22), and had significantly more clinical symptoms during their acute illness. The authors conclude that young females are particularly vulnerable to post COVID-19 syndrome.
Publication date / reference: 26/11/20 Dani et al. Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies. Clin Med (Lond).
Summary: The authors of this study describe six cases of autonomic dysfunction following viral infection during the COVID-19 pandemic (one confirmed COVID-19 case, the remaining suspected). The authors propose that some Long-COVID symptoms may be secondary to viral or immune-mediated disruption of the autonomic nervous system, thus resulting in transient or long-term orthostatic intolerance syndromes. Assessment via active stand test demonstrated an average heart rate rise of under 30 beats per minute, thus not meeting criteria for postural orthostatic tachycardia syndrome. The authors suggest a combination of education, exercise, fluid and salt repletion, avoidance of exacerbating factors, isometric exercises, compression garments and pharmacological treatments based on guidelines and clinical experience.
Summary: Mandal et al.’s cross-sectional study of 384 individuals across three large London hospitals, offers the first report of trajectory in physical and psychological symptom burden, blood markers and chest imaging following hospital discharge. Patients were followed up at a median 54 days post-discharge, with persistence of breathlessness, cough and fatigue being observed in 53%, 34% and 69% of individuals respectively, though with regards to severity it should be noted that persistence was defined as a symptom score of >1 on a scale of 0-10. Psychological symptom burden was also assessed, with 14.6% of participants displaying PHQ2 scores consistent with significant depression. Whilst blood test abnormalities largely improved, persistence in lymphopenia was observed in 7.3% of 247 patients, with D-dimer and CRP remaining elevated in 30.1% of 229 patients and 9.5% of 190 patients respectively. The authors note that these data are in keeping with initial data from smaller COVID-19 cohorts, and that they may aid in identifying patients who may benefit from additional rehabilitation and/or investigation to identify post-COVID complications, though future research is necessary to disentangle complications and deconditioning as causes of persistent dyspnoea.
Publication date / reference: 09/11/2020. Towsend et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One.
Summary: The investigators in this study aimed to establish whether patients remained fatigued (Chalder Fatigue Scale (CFQ-11)) after physical recovery following SARS-CoV-2 infection. Participants (N=128) were recruited from post-COVID-19 clinic, all had confirmed SARS-CoV 2 infection by positive nasopharyngeal swab PCR, all had been more than 6 weeks post date of last acute COVID-19 symptoms (outpatient) or date of discharge (inpatient).
The authors reported a significant prevalence of fatigue (50%) at median follow up of 10 weeks, despite medically deemed recovered from primary illness. They also found significant impact to daily function with almost one third (31%) not returned to employment. Importantly these findings were independent of age and severity of initial infection. There was also an absence of specific immune signature associated with persistent fatigue, no association were found between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. On the other hand, female gender and those with pre-existing diagnosis of depression showed a preponderance in the development of fatigue. The study, though limited by its cross-sectional single centered design, demonstrated a significant medium term fatigue burden and functional impairment following COVID-19 regardless of initial disease severity, and highlights the need for larger cohort, longitudinal studies of COVID -19 patients.
Publication date / reference: 24/04/21. Liu et al. The Efficacy of computerized Cognitive Behavior Therapy (cCBT) for Depressive and Anxiety Symptoms in Patients with COVID-19: Randomized Controlled Trial. J Med Internet Res.
Summary: Randomised controlled trials (RCTs) of interventions for neuropsychiatric complications of COVID-19 are still rare. This week, Liu and colleagues report a multi-centre RCT of computerised cognitive-behavioural therapy (cCBT) for depressive and anxiety symptoms in patients with mild COVID-19 (n=126), versus treatment as usual (n=126). Participants were recruited from five isolation hospitals in China and had mild-to-moderate depressive or anxiety symptoms as defined by the Hamilton Depression Rating Scale (HAM-D) score ≥7 and/or the Hamilton Anxiety Scale (HAM-A) score ≥7. The intervention consisted of several modules, including a cognitive therapy module aiming to minimize patients’ negative thoughts about COVID-19, stress- and sleep-management training, relaxation / mental imagery training, mindfulness meditation, and counting meditation. Participants engaged in self-directed therapy for more than 10 minutes per day, for one week. The primary outcome showed statistically and clinically significant reduction in both HAM-D and HAM-A scores, with the effect persisting at one month followup. Reasons for a cautious interpretation include the lack of blinding, short duration of follow-up, higher drop-out than expected at the follow-up point, and scant information about the COVID-19 clinical status of patients. The effect sizes are also striking for such a short intervention; the reasons for this are not clear. However it is good to see trials beginning to emerge which address how we might treat common neuropsychiatric symptoms arising in patients who have COVID-19, rather than simply assuming existing treatments will ‘map over’ effectively.
Summary: This hospital-based, cross-sectional study examined depression, anxiety and sleep disturbance among COVID-19 infected patients. A group of 100 COVID-19 patients (73% males and 27% females) were selected for this study, based on depression, anxiety and sleep disturbance levels assessed using patient health questionnaire-9 (PHQ-9) scale, generalised anxiety disorder-7 (GAD-7) and Pittsburg sleep quality index (PSQI). The mean age of the patients was 42.90 ± 16.33 years. The results have shown that 27% of patients presented with depression, whilst 67% of patients experienced anxiety (both psychiatric problems were significantly associated with the severity of illness and presence of comorbidity factors). Sleep disturbance affected 62% of COVID-19 patients, which in turn significantly correlated with the severity of illness. This research confirms the detrimental impact of COVID-19 infection on the psychological state of patients, thus highlighting the importance of prompt identification and timely interventions that should be available for these patients.
Publication date / reference: 20/4/21. Liu et al. Effects of group psychological intervention combined with pulmonary rehabilitation exercises on anxiety and sleep disorders in patients with mild coronavirus disease 2019 (COVID-19) infections in a Fangcang hospital. Psychol Health Med.
Summary: This randomised control trial aimed to compare the effectiveness of group psychological intervention based on traditional Chinese medicine and pulmonary rehabilitation exercises with conventional nursing in two randomised cohorts of 70 patients each, from a population of hospitalised COVID-19 patients with mild disease. The intervention group had lower state anxiety questionnaire (SAI) and Pittsburgh sleep quality index scale (PQSI) scores. They concluded their intervention was significantly more effective than conventional nursing methods in mitigating anxiety and sleep disorders for patients in the hospital.
Publication date / reference: 14/04/2021 Capuzzi et al. Initiation of psychotropic medication in hospitalized patients with COVID-19: Association with clinical and biological characteristics. Hum Psychopharmacol.
Summary: This cross-sectional study of 151 inpatients with covid-19 found that 31% were started on some form of psychotropic medication (e.g. anxiolytics, antidepressants, mood stabilizers, antipsychotics) during admission.
Publication date / reference: 08/04/2021 Zhang Z, Feng Y, Song R, Yang D, Duan X. Prevalence of psychiatric diagnosis and related psychopathological symptoms among patients with COVID-19 during the second wave of the pandemic. Global Health.
Summary: This cross-sectional survey (n=119) investigated the mental health outcomes and risk factors of patients infected with COVID-19 and admitted to an isolation hospital during the second wave of the pandemic. Participants were assessed using the Mini International Neuropsychiatric Interview and self-report questionnaires. The authors found high rates of self-reported symptoms of generalised or state anxiety (51.3%), depression (41.2%) and PTSS/PTSD (33.6%). Loneliness was the only shared risk factor across all psychopathological symptoms. The authors recommended that patients with COVID-19 infections should be provided with specific mental health interventions and resources.
Publication date/reference: 08/04/2021. Luykx & Lyn. Are psychiatric disorders risk factors for COVID-19 susceptibility and severity? a two-sample, bidirectional, univariable, and multivariable Mendelian Randomization study. Transl Psychiatry.
Summary: This bidirectional Mendelian randomisation analysis of a large genome-wide association study investigated the relationship between neuropsychiatric disorders and COVID-19. In the univariate analysis, genetic liability to schizophrenia and bipolar disorder increased the risk of COVID-19 (OR = 1.17, 95% CI, 1.06–1.28). However, this was not supported by the multivariate analysis, where body mass index (BMI) was the only consistent association with COVID-19. The authors concluded that there is no proof that neuropsychiatric disorders are a risk for COVID-19 and vice versa and that previously reported associations may be a result of confounding from insufficient adjustments for the BMI.
Publication date / reference: 08/04/2021 Boekhorst et al. The COVID-19 outbreak increases maternal stress during pregnancy, but not the risk for postpartum depression. Arch Womens Ment Health.
Summary: This prospective cohort study of (n=669) women in the Netherlands compared perinatal symptoms of depression and stress during and before the pandemic. During the pandemic, 268 women filled out at least one questionnaire during pregnancy and 59 postpartum. The authors found that pregnancy-specific stress increased significantly in women during the pandemic. They found no increase in depressive symptoms during pregnancy nor an increase in incidence of high levels of postpartum depressive symptoms during the pandemic. They concluded that clinicians should be aware of the potential for increased stress in pregnant women during the pandemic.
Publication date / reference: 06/04/21 Olanipekun et al. Incidence and Severity of Depression Among Recovered African Americans with COVID-19-Associated Respiratory Failure. J Racial Ethn Health Disparities.
Summary: The authors evaluated the incidence and severity of major depression among 73 African American patients within 90 days of recovery from severe COVID-19-associated respiratory failure. Using the PHQ-9 13/73 patients had moderate depression, while 11/73 and 16/73 had moderately severe and severe depression, respectively.
Publication date / reference: 01/04/2021 Diez-Quevedo et al. Mental disorders, psychopharmacological treatments, and mortality in 2,150 COVID-19 Spanish inpatients. Acta Psychiatr Scand.
Summary: This study aimed to explore the relation between mental disorders and psychopharmacological treatments to mortality in 2 150 adult patients with COVID-19 admitted in a tertiary hospital in Badalona (Spain) between March 1 and November 17, 2020. During the year before hospitalisation 957 (44.5%) patients were registered for a mental disorder. Overall 166 patients had de novo diagnosis (11.9% of the population without previous history) and 208 (9.7%) were diagnosed with delirium. Overall 1011 (47.0%) received psychotropic drug prescription during admission and for 767 patients it was a de novo prescription. Most commonly patients were prescribed benzodiazepines (782 patients). Delirium (1.83; 95% CI, 1.19 to 2.82, P=0.006), treatment with an antipsychotic during admission (1.57, 95% CI 1.10 to 2.82 P=.01) and history of mood disorder (1.57; 95% CI, 1.03 to 2.40 P=.04) were associated with higher mortality rate, while treatment with antidepressants (0.34; 95% CI, 0.17 to 0.67 P=.002) and anxiolytics/hypnotics (0.33; 95% CI, 0.18 to 0.62; P=0.001) were associated with lower mortality rate.
Publication date / reference: 6/4/2021 Olanipekun et al. Incidence and Severity of Depression Among Recovered African Americans with COVID-19-Associated Respiratory Failure. J Racial Ethn Health Disparities.
Summary: This cohort study aimed to evaluate the incidence and severity of major depression among African American patients within 90 days of recovery from severe COVID-19-associated respiratory failure. The authors screened (n=73) patients and found that the median age was 52.5 years and 65% were males. The most common comorbidities were hypertension (66%) and diabetes mellitus (51%). 44% had a diagnosis of major depressive disorder (MDD). The incidence of MDD was higher among females (69%) compared to males, in patients >75 years (66%) and those with multiple comorbidities (45%). 18% had moderate depression, while 15% and 22% had moderately severe and severe depression, respectively. Only 26% were receiving treatment for depression at the time of this survey. They concluded that the incidence of depression without prior psychiatric conditions who recovered from severe COVID-19 infection was 44%. More than 70% of these patients were not receiving treatment for depression.
Publication date / reference: 03/04/2021 Mahmoudi et al. A mediating role for mental health in associations between COVID-19-related self-stigma, PTSD, quality of life, and insomnia among patients recovered from COVID-19. Brain Behav.
Summary: This cross-sectional cohort study (n=844) to investigate the relationship between self-stigma for those infected and other neuropsychiatric factors. Patients were interviewed after the acute illness following hospitalisation. Those with severe underlying mental health disorders were excluded. The authors found that mental health as a mediator had a negative relationship with COVID-19-related self-stigma, PTSD and insomnia but positive relationship with quality of life. Mental health mediated the effect of COVID-19-related self-stigma on quality of life for patients after infection. The results from this study support the central role of mental health in mediating COVID-19-related self-stigma.
Publication date / reference: 29/03/2021 Kikutani et al., COVID-19 Infection-Related Weight Loss Decreases Eating/Swallowing Function in Schizophrenic Patients Nutrients
Summary: This retrospective study in Tokyo involved (n=44) confirmed COVID-19 patients in a psychiatric ward being treated for Schizophrenia, and investigated if there were any associations between swallowing function and COVID-19 infection. After COVID-infection, they found 13 patients were malnourished (basis of BMI) and they found 14 patients had a decreased FILS (Food Intake Level Scale) score (presence of eating/swallowing disorder). The authors conclude that post-infection changes to quality of life should be considered and in schizophrenic patients who may be at risk of swallowing issues, further detriment is a risk factor.
Publication date / reference: 29/03/2021 Tarsitani et al., Post-traumatic Stress Disorder Among COVID-19 Survivors at 3-Month Follow-up After Hospital Discharge J Gen Intern Med
Summary: In this paper, the authors conducted a cohort follow-up study in a large Italian academic COVID-19 hospital. 115 recruited survivors were contacted by telephone 3 months after discharge to home care. The Posttraumatic Stress Disorder Checklist for DSM-5 was administered. Multivariate logistic regression models were used to analyse risk factors for the development of PTSD. A total of 10.4% of the sample received a PCL-5-based diagnosis of PTSD.
Publication date / reference: 04/03/2021 Ismael et al. Substance use in mild-COVID-19 patients: a retrospective study. Front Public Health.
Summary: This retrospective cohort study looked into the prevalence of substance abuse amongst Brazilian patients with mild-COVID-19 defined as no alarming symptoms or need for in-person consultation (n=993). After the active phase (median=108 days) of infection patients were asked about retrospective substance abuse before, during and after COVID-19 illness. The authors found that alcohol and tobacco use declined after acute illness, however higher pre-COVID levels of these substances was associated with post-COVID cannabis use. Ismael and colleagues found no association between substance use and COVID-19 symptomatology.
Publication date / reference: 2/3/2021. Merzon et al. The Association between ADHD and the Severity of COVID-19 Infection. J Atten Disord.
Summary: Data regarding 1,870 individuals with ADHD who had tested positive for SARS-Cov-2 (RT-PCR confirmed) was extracted from a clinical database. ADHD was found to be associated with increased rates of hospitalisation and increased severity of COVID-19 symptoms.
Publication date / reference: 15/03/21 Moni et al. COVID-19 patient transcriptomic and genomic profiling reveals comorbidity interactions with psychiatric disorders. Transl Psychiatry.
Summary: This study evaluated the genetic profile of patients with COVID-19 and psychotic disorders. In particular it looked at whole transcriptome and immune factor transcript data in peripheral blood and mononuclear cells in patients with either COVID-19 or psychiatric disorders.COVID-19 patients had peripheral blood immune system profiles that overlapped with those of patients with psychiatric conditions. This study also looked at genome-wide association study (GWAS) data for symptomatic COVID-19 patients compared to GWAS data for patients with bipolar disorder, PTSD and Schizophrenia. These studies revealed altered signalling and ontology pathways shared by COVID-19 patients and the psychiatric disorders. Finally, co-expression and network analyses identified gene clusters common to the conditions. From the pathways identified, PTSD profiles were the most highly correlated with COVID-19, which the authors argued was consistent with stress-immune system interactions seen in PTSD. They also refound common inflammatory pathways that may exacerbate psychiatric disorders, which may support the usage of anti-inflammatory medications in these patients. The authors argue that this genetic evidence may provide a basis for therapeutic treatment of SARS-COV-2 infected psychiatric patients
Publication date / reference: 26/03/2021 Cardenas et al., Prevalence of COVID 19 Positive Cases Presenting to a Psychiatric Emergency Room. Community Ment Health J.
Summary: This cross-sectional retrospective chart review determined point-prevalence of SARS-CoV-2 infection and characteristics of those infected in the psychiatric emergency room setting. 2.2% (n=23 patients) tested positive for SARS-CoV-2 and the majority of these were homeless or from congregate living settings. This stresses the importance of asymptomatic SARS-CoV-2 screening in the vulnerable homeless/congregate living setting population.
Publication date / reference: 02/03/2021 Crespo-Facorro et al. Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis. Front Pharmacol.
Summary: In this exploratory study, Crespo-Facorro et al describe transcriptomic analysis of blood samples from 57 non-affective psychosis patients and comparison with RNA-seq data from three COVID-19 patients and three healthy controls in Wuhan. It was found that 82 of the 377 genes altered in expression by 3 months of aripiprazole treatment, also differed in expression in COVID-19 patients. Pathway analyses of differentially expressed genes indicated the most significant pathways were immune and inflammatory mechanism-related. The authors do note the limitation of only having included three COVID-19 patients for whom there is little knowledge of characteristics.
Publication date / reference: 26/02/2021 Putri et al., Psychological distress assessment among patients with suspected and confirmed COVID-19: A cohort study. J Formos Med Assoc
Summary: This cohort study of COVID-19 patients aimed to characterise the psychological burden of COVID-19 over time, from hospital admission, discharge to outpatient follow-up. 109 patients participated in the study, the main finding was 16.5% reported psychological distress on hospital admission and this showed a distinct time-dependent decline.
Publication date / reference: 01/02/2021 Zhou et al. A randomized trial in the investigation of anxiety and depression in patients with coronavirus disease 2019 (COVID-19). Ann Palliat Med.
Summary: Although this paper is titled a ‘randomised trial’, that isn’t true in the sense many of our readers would understand. Instead, the authors ‘randomly’ selected 65 hospitalised COVID-19 patients and performed a cross-sectional survey of anxiety and depressive symptoms. Point prevalences of anxiety and depression were 26% and 42% respectively. Perhaps the most interesting finding was that neither anxiety nor depression were associated with severity of COVID-19 illness.
Publication date / reference: 17/03/2021 Mongodi et al. High prevalence of acute stress disorder and persisting symptoms in ICU survivors after COVID-19. Intensive Care Med.
Summary: In this letter, Mongodi et al. describe the findings of follow-up hospital visits for 47 patients who were admitted to an ICU for COVID-19, at least 1 month after hospital discharge. The Impact of Event Scale–Revised (IES-R) was used to screen for acute stress disorder (ASD), defined by a score ≥ 33. Median IES-R score was 30, with 19/47 patients showing ASD. Among subscales, intrusion average score was higher than avoidance and both were higher than hyperarousal. No significant difference in patients’ characteristics, length of stay in ICU/hospital, need and length of invasive/non-invasive ventilation and drugs was observed comparing ASD and non-ASD patients
Publication date / reference: 17/03/2021 Shaunak et al. COVID-19 symptom surveillance in immunocompromised children and young people in the UK: a prospective observational cohort study. BMJ Open.
Summary: In this prospective cohort study Shaunak et al. aimed to describe the frequency of symptoms consistent with SARS-CoV-2 infection in immunocompromised children and young people; prevalence of patient/parent anxiety in regards to SARS-CoV-19 infection was also assessed. Patients filled in a weekly online questionnaire for a year (follow-up is ongoing), but this publication reports on results up to 4 July 2020 (when lockdown restrictions were eased). The study included 1490 immunocompromised children from 46 centres in the UK. Participants most frequently reported joint pain, fatigue, headache, nausea and muscle pain. None of the study participants tested positive for SARS-CoV-19 infection. About 62% of patients reported high levels of anxiety and levels remained high through follow-up.
Publication date / reference: 01/03/2021 Perlis et al., Association of Acute Symptoms of COVID-19 and Symptoms of Depression in Adults. JAMA Netw Open.
Summary: This study aimed to see if there was an association between acute COVID-19 symptoms and subsequent depressive symptoms. 3904 individuals participated in this study with prior COVID-19 illness, the PHQ-9 screening tool was then used to screen for symptoms of depression (score of 10 or higher considered moderate depression). Sociodemographic factors were also taken into account in the analysis. Over 52.4% of the COVID-19 sample studied met criteria for moderate or more severe symptoms of depression. Symptoms were more frequent in younger respondents, respondents who were male and who self-reported greater COVID-19 severity.
Publication date / reference: 02/03/2021 Özlü et al. The effects of progressive muscle relaxation exercises on the anxiety and sleep quality of patients with COVID-19: A randomized controlled study. Perspect Psychiatr Care.
Summary: The authors of this experimental study trialled muscle relaxation exercises on 33 patients with COVID-19 and results were compared with those of 34 COVID-19 patients in a control group. Significant differences were noted between both groups’ mean post-test scores on the State-Trait Anxiety Inventory and the Richards-Campbell Sleep Questionnaire. In-group comparison of the experimental group found a significant difference between mean pretest and posttest scores on the State Anxiety Scale. In-group comparison of the control group found no statistically significant changes in their mean pretest and posttest scores on the State Anxiety Scale.
Summary: This was a longitudinal cohort study looking at the prevalence of PTSD symptoms in post-COVID infected inpatient and outpatients in a region in Norway (n=583). The median response was 116 days after COVID infection. PTSD prevalence was 9.5% (11) in hospitalised cohort and 7.0% (32) in non-hospitalised patients. Their findings suggest risk factors for developing PTSD symptoms post-COVID included female sex and those not born in Norway. Other risk factors in the community patient cohort included: previous depression, and higher severity of initial COVID symptoms.
Publication date / reference: 20/02/2021. Parizad et al. Effect of guided imagery on anxiety, muscle pain, and vital signs in patients with COVID-19: A randomized controlled trial. Complement Ther Clin Pract.
Summary: This is a randomised controlled trial which evaluated the effect of guided imagery on reported levels of anxiety, muscle pain and other physiological measures in 110 patients with COVID-19. The intervention consisted of 10 sessions of recorded visualisation and relaxation exercises, compared to control. The authors found a significant decrease in state anxiety (t = -3.829), trait anxiety (t = -2.946), pain quality (t = -4.223, p < .001) and pain intensity (t = -3.068, p = .003) in the intervention compared to control group. This is preliminary evidence demonstrating a potential benefit for visualisation and guided imagery techniques in patients with anxiety and COVID-19.
Publication date / reference: 04/03/2021 Moayed et al. Depression, Anxiety, and Stress Among Patients with COVID-19: A Cross-Sectional Study Adv Exp Med Biol
Summary: This is a cross-sectional study. Patients with a confirmed diagnosis with COVID-19 were included in the study by census sampling. Assessment of depression, stress, and anxiety was performed using the DASS-21 questionnaire. The questionnaires were completed by 221 patients with COVID-19 infection (204 males, 17 females). Results indicated that the mean scores of depression and anxiety were at “extremely severe” levels, while stress levels were “severe
Publication date / reference: 22/2/21 Moradi et al. Psychological reactions of COVID-19 patients to the stress caused by the disease crisis: A descriptive phenomenological study. Perspect Psychiatr Care.
Summary: Moradi and colleagues conducted a retrospective qualitative study using semi-structured interviews of 14 patients (mean age 35.37) who had all been hospitalised for COVID-19. Data was analysed using Colaizzi’s seven-step method, with two broad themes emerging; “self-moderating the effect of stress” and “psychological maladaptation”. Psychological maladaptation took the form of depression, regret and self-blaming, whilst self-moderating the effects of stress encompassed spiritual meditation, distraction and avoidance
Publication date / reference: 23/02/2021 Kimura et al. Relationships between changes due to COVID-19 pandemic and the depressive and anxiety symptoms among mothers of infants and/or preschoolers: a prospective follow-up study from pre-COVID-19 Japan. BMJ Open.
Summary: In their prospective study Kimura et al. aimed to establish the association between changes due to the COVID-19 pandemic and incidence of depressive and anxiety in mothers, aged 20-29 with young children (aged 0-6). Of 4700 who initially took part in an online survey, overall, 2286 participants were included in the analysis after the follow-up survey in June 2020; depressive and anxiety symptoms were measured by Kessler Psychological Distress Scale (K6). Overall, 151 patients (6.6%) had newly developed depressive and anxiety symptoms during the follow-up period. The occurrence of depression and anxiety was significantly correlated to shortage of relaxation time (AOR 1.61, 95% CI 1.06 to 2.47), increased difficulty in child rearing (AOR 1.89, 95% CI 1.32 to 2.70), increased partner aggression (AOR 2.93, 95% CI 1.42 to 6.05) and an increased sense of unfairness (AOR 1.74, 95% CI 1.10 to 2.73).
Publication date / reference: 19/02/21. Lee et al. Association between mental illness and COVID-19 in South Korea: a post-hoc analysis. Lancet Psychiatry.
Summary: The authors present a post-hoc analysis in response to correspondence to their prior article. They report that in comparison to controls, the risk of SARS-CoV-2 infection was greater in patients who mis-used alcohol or drugs, but was not associated with patients having anxiety and stress-related disorders, mood disorders, personality disorders, or eating disorders. Mechanisms underlying the association were speculated to include biological consequences of alcohol or drug use, or social consequences of inebriation such as lower concern for social distancing.
Publication date / reference: 19/02/2021 Canal-Rivero et al. Lower risk of SARS-CoV2 infection in individuals with severe mental disorders on antipsychotic treatment: A retrospective epidemiological study in a representative Spanish population. Schizophr Res.
Summary: Canal-Rivero and colleagues present a retrospective epidemiological study investigating the risk of SARS-CoV2 infection in patients with severe mental disorders (SMD), treated with long acting injectable (LAI) antipsychotic treatment. Between February to November 2020, the authors compared a cohort of non-SMD patients (n=557576) and a cohort of n=698 SMD patients. The authors found that a significantly reduced proportion of patients with SMD (1.3%) was infected by COVID-19 , compared to the non-SMD cohort (4.1%) (p ≤0.001). Similarly, patients with SMD had a lower proportion of hospital admissions (8.5% vs 0%), ICU admissions (0.9% vs 0%) and deaths (1.1% vs 0%) – although these differences were not statistically significant. These findings add to the small body of literature suggesting that antipsychotics may play a role in preventing and attenuating the severity of COVID-19 (summarised by the authors at the start of this letter). The authors acknowledge that this association is complex and that this study has not been able to account for all the likely contributing factors.
Publication date / reference: 8/02/2021 Xu et al.Depression and insomnia in COVID-19 survivors: a cross-sectional survey from Chinese rehabilitation centers in Anhui province. Sleep Med.
Summary: This prospective cross-sectional study included 121 patients with COVID-19 two weeks after discharge from Chinese rehabilitation centers in Anhui province. Prevalence and the severity of depression and insomnia was assessed by the Insomnia Severity Index (ISI), and the Center for Epidemiology Scale for Depression (CES-D). Overall, 12 people (9.9%) had clinically significant depression (>16 points on CES-D) and 32 (26.4%) were diagnosed with insomnia based on ISI score >8. Patients with mental and physical impairment were at least two times more likely to experience depression (P = 0.035, OR = 2.1, 95% CI = [1.1; 4.1]) or insomnia (P = 0.005, OR = 2.1, 95% CI = [1.2; 3.5]). Need for psychological assistance correlated with the prevalence of depression (P = 0.004, OR = 18.4, 95% CI = [2.6; 132.5]) while age was only a slight risk factor for insomnia (P = 0.002, OR = 1.1, 95% CI = [1.0; 1.2]).
Publication date / reference: 28/01/2021 Graaf et al. Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach. EClinicalMedicine.
Summary: This study aimed to evaluate outpatients six weeks after discharge and compare between patients admitted to the general ward and ICU, and between patients with a high versus low functional status. The authors included 81 patients (41% ICU). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. They concluded that most patients suffered from functional limitations. Dyspnea on exertion was most frequent and could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.
Publication date / reference: 18/02/2021 Wang et al. Acute psychological impact on COVID-19 patients in Hubei: a multicenter observational study. Transl Psych.
Summary: In this cross-sectional study of hospitalised but non-critical covid-19 patients in China, a number of online screening tools were administered to those who were well enough to respond. The authors reported that 66% of respondents had ‘somatisation symptoms’ (based on >4 on the PHQ-15 scale), however it would be unfair to label these symptoms as ‘psychological’ (as the authors state) given that the patients were by definition physically unwell with covid-19 at the time. Depressive symptoms (PHQ-9) were found in 53% and anxiety symptoms (GAD-7) in 46%. Suicidal ideation was found in a fifth. These results show high levels of psychiatric symptomatology in the acute phase of covid-19, however the study is significantly limited by the use of screening tools with low cut-off scores.
Publication date / reference: 18/02/2021. Janiri et al. Posttraumatic Stress Disorder in Patients After Severe COVID-19 Infection. JAMA Psychiatry.
Summary: In this Research Letter to the Editor Janiri et al. reported results from a cross-sectional study which aimed to establish the prevalence of PTSD among 381 patients who recovered from COVID-19 after an acute infection. About 30.2% (115) patients had PTSD (diagnosed with criterion-standard Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)). The most common additional diagnosis in all 381 patients were depressive episode – 17.3% (66 patients) and generalized anxiety disorder- 7.0% (27 patients). PTSD was more common in women, in patients with a history of psychiatric disorders and delirium during the acute stage.
Publication date / reference: 14/01/2021 Bonazza et al. Psychological outcomes after hospitalization for COVID-19: data from a multidisciplinary follow-up screening program for recovered patients. Res Psychother.
Summary: This retrospective observational study of 261 patients noted symptoms of anxiety (28%), depression (17%) and PTSD (36.4%) in patients with negative outcomes being associated with female gender and anxiety symptoms being negatively correlated with patient age. 13.8% underwent a psychological visit and 6.1% were taken in charge for psychological support.
Publication date / reference: 11/02/2021 Ferrario et al. The psychological experience and intervention in post-acute COVID-19 inpatients. Neuropsychatr Dis Treat.
Summary: In this study of 181 hospitalized COVID-19 patients, 47.5% underwent psychological assessment. The most common psychological issues were acute stress disorders (18.6%), anxious and demoralization symptoms (26.7%), depression (10.5%%), and troublesome grief (8.1%).
Publication date / reference: 24/12/2020 Shousha et al. Psychiatric morbidities and Coping strategies in patients with different Coronavirus disease-2019 severities and chronic medical diseases: A multicenter cross-sectional study. MedRxic preprint.
Summary: This multi-centre cross sectional study aimed to explore the difference in anxiety, depression and coping strategies of individuals with or without chronic medical illnesses (CMI). 199 patients responded to a survey of which 46.73% had CMI. The most common coping mechanisms used by both groups were religion, emotional support, use of information and acceptance.
Publication date / reference: 09/02/2021 Hoertel et al. Observational Study of Chlorpromazine in Hospitalized Patients with COVID-19. Clin Drug Investig.
Summary: This retrospective study aimed to examine the association between chlorpromazine use and mortality among adult COVID-19 inpatients. The authors defined baseline as the date of first prescription of chlorpromazine during hospitalization for COVID-19 outside ICUs and compared the death endpoint between those who received chlorpromazine and those who did not. They found that 55 out of the 14,340 (0.4%) patients received chlorpromazine. Over a mean follow-up of 14.3 days, death occurred in 23.6% who received chlorpromazine and 9.0% who did not. There was no significant association between chlorpromazine use and mortality (HR=2.01). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67) and a multivariable Cox regression that indicated a significant positive association (HR 3.10). They concluded that chlorpromazine prescribed at a mean daily dose of 70.8 mg was not associated with reduced mortality.
Publication date / reference: 28/10/2021 Turan et al. Characteristics and outcomes of COVID-19 inpatients who underwent psychiatric consultations. Asian J Psychiatr.
Summary: This descriptive study analysed the records of covid-19 patients referred for inpatient psychiatric input. Supporting previous data, delirium was the most common diagnosis (40%), with adjustment disorder, depressive disorder, and anxiety disorder making up the rest.
Publication date / reference: 09/02/2021 Chamberlain et al. Post-traumatic stress disorder symptoms in COVID-19 survivors: online population survey. BJPsych Open
Summary: This study examined post-traumatic stress disorder (PTSD) symptoms in 13,049 survivors of suspected or confirmed COVID-19, from the UK general population, as a function of severity and hospital admission status. Significantly elevated rates of PTSD were found in those requiring at home medical support or those requiring hospital admission with and without ventilation as compared to those with mild COVID-19.
Publication date / reference: 08/02/2021 Chen et al. Prevalence and predictors of posttraumatic stress disorder, depression and anxiety among hospitalized patients with coronavirus disease 2019 in China BMC Psychiatry
Summary: The authors aimed to study the mental health of hospitalized patients diagnosed with COVID-19. The authors used various checklists and questionnaires to examine post-traumatic stress disorder (PTSD), depression, anxiety, trauma exposure, resilience and perceived social support among 898 patients who were hospitalized after being diagnosed with COVID-19 in China. Results showed that hospitalized patients who were more impacted by negative news reports, had greater exposure to traumatic experiences, and had lower levels of perceived social support, reported higher PTSD, depression and anxiety.
Publication date / reference: 03/02/2021. Liu et al. Investigation and analysis of psychological stress among non-severe COVID-19 patients. J Mol Cell Biol.
Summary: Cross-sectional Questionnaire study of the impact of psychological stress in non-severe COVID-19 patients (N=90). Data on stress perception (PSS-10), PTSD symptoms (PCL-5) and symptoms of anxiety (HADS-A) and depression HADS-D) were collected. Factors such as age, gender, marital status and education levels were found to have significant associations with higher stress, PTSD, depression and anxiety symptoms in this cohort of patients, and the prevalence of these symptoms were higher than that found in the general population. The study finding is limited by the small sample size, self-reported data and lack of control for confounders.
Publication date / reference: 21/01/2021. Syed et al. Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness – A case series. Int J Psychiatry Med.
Summary: Case series of 4 patients who were on psychotropic polypharmacy, admitted to psychiatric facility with COVID-19 delirium. Authors aimed to highlight the diagnostic and management challenges clinicians faced and the importance of multi-disciplinary collaboration in caring for these patients.
Publication date / reference: 3/2/2021. Tsai et al. Mental Health and Psychosocial Characteristics Associated With COVID-19 Among U.S. Adults Psychiatry Online
Summary: In this study, the authors aimed to examine the psychosocial and mental health characteristics associated with COVID-19 infection. An online survey that asked about COVID-19 status, social support, and mental health was used to recruit a national sample of 6,607 low- and middle-income adults; 354 reported a positive COVID-19 test, 1,819 reported a negative test, and 4,434 reported not being tested in May or June 2020. Compared with the COVID-19− and untested groups, the COVID-19+ group was more likely to consist of veterans and have individuals with a history of homelessness or who reported a greater number of close friends or relatives, greater social support, and a greater sense of loneliness.
Publication date / reference: 28/01/2021 Bonaccorso et al. Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report. Brain Behav Immun Health.
The authors of this small study lay claim to the first report suggesting a drop in absolute neutrophil in patients taking clozapine whilst infected with SARS-CoV-2 infection. In these patients the drop was transitory with the patients reaching baseline levels after the resolution of COVID-19. Caution should be taken when reading this study given the small dataset and the lack of other possible explanatory variables into the regression analysis.
Publication date / reference: 01/11/2020 Yang et al. Pre-pandemic psychiatric disorders and risk of COVID-19: a UK Biobank cohort analysis.Lancet Healthy Longev.
Summary: In their retrospective cohort analysis Yang et al. aimed to examine the prevalence of pre-pandemic psychiatric disorders (mood disorders, anxiety, stress-related disorder, substance misuse, psychotic disorders) and the subsequent risk of COVID-19 in 421 014 participants in UK Biobank cohort. Of 50 509 patients with pre-existing psychiatric disorder, 442 (0.9%) were COVID-19 cases while 1509 (0.4%) of 370 205 without pre-existing psychiatric disorders had COVID-19. The adjusted model showed OR 1·44 (95% CI 1·28–1·62) for all COVID-19 cases, OR 1·55 (1·34–1·78) for inpatient COVID-19 cases, and OR 2·03 (1·59–2·59) for COVID-19-related deaths, showing that patients with pre-existing psychiatric disorder were at elevated risk of COVID-19.
Publication date / reference: 2020. Theano et al. SARSCoV-2 Psychosomatic Effects and Fear of Stigma on the Discharge Day of Infected Individuals: SAPFO Study. Psychiatr Danub.
Summary: This non-intervention prospective study aimed to evaluate the psychosomatic effects and the fear of stigma which patients may face after the end of treatment and discharge from hospital. The authors evaluated patients using 5 topic questionnaires: pain/discomfort, anxiety/distress, fear/worries, stigma and tolerance of treatment. They found that females and patients younger than 40 years old had more worries and fears. Significant factors were days of hospitalization, days of fever and need of oxygen therapy. Patients hospitalized more than 10 days, particularly in isolation negative pressure rooms, with persistent fever more than 7 days and need of oxygen therapy had more anxiety, worries for their clinical condition and fear of stigma. The majority of patients (80%) were expecting to face moderate to severe problems with family members, friends and colleagues underlying the dimensions of stigma. They concluded that it is crucial to evaluate the psychosocial aspects of this infection and limit the stigma which patients may face returning to their daily routine.
Publication/date reference: 18/01/2021. The Psychological Burden of COVID-19 Stigma: Evaluation of the Mental Health of Isolated Mild Condition COVID-19 Patients. J Korean Med Sci.
Summary: This was a retrospective observational cohort study of mental health problems in COVID-19 patients admitted to a community treatment center in Korea (N=107). At time of admission (baseline), psychiatric history and assessment were evaluated using the PHQ-2 (to assess major depressive disorder symptoms) and GAD-2 (to assess anxiety). Weekly mental health assessments were done using a variety of self-reporting questionnaires: PHQ-9 (assess depression), GAD-7 (assess anxiety), P4 suicidality screener, PCL-5 (assess PTSD), PHQ-15 (assess somatic symptom severity), MERS stigma scale (COVID-19 stigma). The results suggest social mitigation of COVID-19 related stigma and care of pre-existing psychiatric illnesses are valuable measures of mental health during a crisis period.
Publication/date reference: 11/01/2021. The Effect of COVID-19 Anxiety on General Health: the Role of COVID-19 Coping. Int Journal of Mental Health Addiction.
Summary: This study aimed to contribute to the extant literature in general health during the COVID-19 pandemic and incorporated the study of COVID-19 anxiety and coping using a large Turkish sample. Participants (70% females) included 4624 adults recruited through convenient sampling. Authors performed exploratory, confirmatory factor as well as correlation analysis and also did regression analysis, in which a path model was constructed whereby the COVID-19 anxiety was an exogenous variable, the COVID-19 coping was the mediating variable, and general health was the dependent variable. Authors found COVID-19 anxiety was negatively related with COVID-19 coping and general health. COVID-19 coping had a positive relationship with general health. Hierarchical multiple regression analyses revealed that COVID-19 coping partially mediated the relationship between COVID-19 anxiety and general health.
Publication date / reference: 07/01/2021. Arbelo et al. Psychiatric Clinical Profiles and Pharmacological Interactions in COVID-19 Inpatients Referred to a Consultation Liaison Psychiatry Unit: a Cross-Sectional Study. Psychiatr Q.
Summary: In this cross-sectional study Arbelo et al. described the psychiatric clinical profile and pharmacological interactions in 71 hospitalised patients with COVID-19 who were referred to a Consultation- Liaison Psychiatry (CLP) unit in a general university hospital in Barcelona, Spain. Non-severe mental illness was most prevalent with 33patients (46.5%) with clinical presentation of mild-to moderate depression, adjustment disorder, substance abuse and etc. Twenty five patients (35.2%) had delirium and 13 patients (18.3%) had severe mental illness (SMI), such as schizophrenia, bipolar disorder or other. In terms of pharmacological interactions between anti-COVID19 and psychiatric drugs, the authors reported mainly drowsiness (4.3%) and borderline QTc prolongation (1.5%).
Publication date / reference: 09/12/2020 Zhang et al. Mental health outcomes among patients from Fangcang shelter hospitals exposed to coronavirus disease 2019: An observational cross-sectional study. Chronic Dis Transl Med.
Summary: In their study Zhang et al. reported levels of sleep quality (Self Rating Scale of Sleep; SRSS), anxiety (7-item Generalized Anxiety Disorder; GAD-7), depression (9-item Patient Health Questionnaire; PHQ-9), self-efficacy, stress (Whiteley Index; WI-7; Connor-Davidson Resilience Scale;CD-RISC; Impact of Event Scale-Revised; IES-R) and social support (Social Support Rating Scale; SSRS) in patients with mild or moderate COVID-19 illness from Jingxia Fangcang shelter hospital in Wuhan, China. Out of 129 participants, who completed the survey, 64 (49.6%) had depressive or anxiety symptoms and these symptoms were highly correlated to sleep disturbances and hypochondriasis (all r > 0.50, P < 0.01). Patients with mental health symptoms had lower levels of psychological resilience.
Publication date / reference: 17/12/2020 Moradi et al. Psychological disturbances of survivors throughout COVID-19 crisis: a qualitative study. BMC Psychiatry.
Summary: This qualitative study, the first of its type this blog team is aware of, performed a semi-structured phenomenological and thematic analysis on the experience of fourteen survivors of COVID-19, aged 29-48. The three principal experiential themes extracted were the feeling on unknowiness about the virus and their prognosis (‘living in limbo’), being required to experience their illness in isolation (‘psychological distress behind the wall’), and worry about contagian, particularly to family members (‘psychological burden of being a carrier’).
Publication date / reference: 16/12/2020 Carpiniella et al. Psychiatry during the Covid-19 pandemic: a survey on mental health departments in Italy. BMC Psychiatry.
Summary: This survey aimed to canvas opinion from community and inpatient psychiatrists in Italy, including teams who had dealt with covid-19 positive patients. One fifth of community mental health teams eported increased aggression from patients during the pandemic. Echoing other data, opinion represented a decrease in the overall number of inpatient admissions, with a proportionate increase in involuntary detentions.
Publication date / reference: 16/12/2020 White et al. Changes in Alcohol Consumption Among College Students Due to COVID-19: Effects of Campus Closure and Residential Change. J Stud Alcohol Drugs
Summary: In their publication White et al. presented the results on a sample of 312 college students in order to compare their drinking behaviour pre- and post- campus closure. The sample was derived from the larger Campus Alcohol and Marihuana Study. While drinking frequency increased from 3.0 days to 3.2 days per week, t (296) = -2.11, p < .05 (Cohen’s d = 0.12), students consumed decreased the number of weekly drinks 11.5 to 9.9 drinks per week, t(296) = 2.65, p < .01 (d = 0.15), as well as the number of daily drinks from 4.9 to 3.3 drinks, t(296) = 8.05, p < .001 (d = 0.47). Students, who moved home from their peers drank less frequently than those who remained with their peers post-closure.
Publication date / reference:15/12/2020 Stojanov et al. The risk for nonpsychotic postpartum mood and anxiety disorders during the COVID-19 pandemic. Int J Psychiatry Med.
The authors have performed an analytical study to find out risk factors for finding out risk factors leading to nonpsychotic postpartum mood and anxiety disorders during the COVID-19 pandemic. Quarantine, and social isolation, the absence of social support, as well as having emotional problems were found to be major risk factors. Postpartum women were more anxious and had feelings of helplessness during social isolation. Though matching for age has been done, there could be additional factors like previous bad obstetric history etc. which also may need to be looked at.
Publication date / reference:14/12/2020 Szajnoga et al. COVID-19 lockdown leads to changes in alcohol consumption patterns. Results from the Polish national survey. J Addict. Dis.
Summary: In their publication Szajnoga et al. present the results of a population survey on professional activity and alcohol consumption, conducted in April 2020. Out of 4072 participants included in this study, 57.2% (2331 respondents) declared a change in alcohol consumption, of which 731 (17.9%) drank alcohol more often, while 39.3% (1600) drank more rarely. Male gender, age 18-24 years, living in big cities and working remotely were associated with higher frequency of alcohol consumption.
Publication date / reference: 12/12/2020 Robillard et al. Social, financial and psychological stress during an emerging pandemic: observations from a population survey in the acute phase of COVID-19. BMJ Open.
Summary: Robillard and colleagues present the results of a population survey involving 6040 participants, focusing on social, financial and psychosocial stress from the COVID-19 pandemic. Stress changes were measured using Cohen’s Perceived Stress Scale (PSS). Unsurprisingly, they found that PSS scores increased from low levels before the outbreak to moderate levels during the outbreak. Numerous factors were associated with this increase (full list in abstract), many of which are stressors in themselves.
Publication date / reference: 09/12/2020 Fancourt et al. Trajectories of anxiety and depressive symptoms during enforced isolation due to COVID-19 in England: a longitudinal observational study. Lancet Psychiatry.
Summary: This prospective longitudinal observational study, based on data from the UCL COVID- 19 study used latent growth models to analyse the trajectories of anxiety (measured with the Generalised Anxiety Disorder assessment; GAD) and depression (measured with Patient Health Questionnaire, PHQ), measured weekly from March 2020 to August 2020. The results based on a sample 36 520 participants showed that levels of anxiety and depression were at their highest at the beginning of lockdown, but rapidly decreased in the first 20 weeks after its introduction; this decrease was fastest during strict lockdown (week 2 to 5) after which symptom levels remained stable, regardless of the introduction of further measures. Risk factors for higher levels of anxiety and depression included female gender, younger age, lower educational status or income, history of mental health condition, living alone or with children.
Publication date / reference: 11/12/20 Tambling et al. Measuring cumulative stressfulness: psychometric properties of the COVID-19 stressors scale. Health Educ Behav.
Publication date / reference: 19/11/20 Escolà-Gascón et al. Measuring Psychosocial Reactions to COVID-19: The COVID Reaction Scales (COVID-RS) as a New Assessment Tool. Front Psychol.
Summary: This paper assessed a novel assessment tool for investigating psychological well-being called the COVID- Reaction Scale (COVID-RS). They assessed 667 individuals in five dimensions of psychopathological reactions and found that quarantine increases and induces these reactions with loneliness relative to the number of people the subject lives with. They state the assessment tool is valid and reliable and can be used to measure dysfunctional reactions.
Publication date / reference: 17/10/2020. Sun et al. A systematic review involving 11,187 participants evaluating the impact of COVID-19 on anxiety and depression in pregnant women. J PsychoSom Obstet Gynaecol.
Summary: This meta analysis investigated the occurrence of anxiety and/or depression in 11,187 pregnant women as archived on MEDLINE, EMBASE and Cochrane Library from December 2019 to July 2020. A random-effects meta analysis was employed and significant heterogeneity was detected in the participants of the 15 studies. The prevalence of anxiety and depression was higher in pregnant women than in controls. The prevalence of anxiety was 34% , depression 30% and that of both anxiety and depression was 18%.
Publication date / reference: 25/11/2020 El Sayed et al. Post COVID-19 Fatigue and anhedonia: A cross-sectional study and their correlation to post-recovery period. Neuropsychopharm Rep.
Summary: This study explored the correlation between a commonly experienced post COVID-19 symptom – fatigue and anhedonia. The authors also aimed to study whether there were any implications on the severity of these psychiatric manifestations dependent on the duration after 2 consecutive PCR-negative tests. Two outcome measures (SAAS – Self Assessment Anhedonia Scale and FAS – Fatigue Assessment Scale) were used to study outcomes. Results showed high scores of various subtypes of SAAS and FAS in the studied group. Positive statistically significant correlation was seen between fatigue and anhedonia in Post COVID-19 group. Duration of after recovery showed negative statistically significant correlation with anhedonia and fatigue in the group.
Summary: The authors of this single-centre study aimed to explore the prevalence and factors linked to anxiety and depression in hospitalized patients with COVID-19, and to determine the effect of a “psychological-behavioural intervention” on anxiety and depression of hospitalised patients with COVID-19. Using the HADS scale with thresholds of 8+, 50 (34.7%) and 31 (28.5%) participants presented symptoms of anxiety and depression respectively, and 26/144 (18%) of patients scored above threshold on both. These 26 patients were randomised to a ten-day intervention emphasising the role of breathing exercises and social support, or usual care control. HADS scores were significantly reduced in the intervention group. There was a trend (p<0.1) to improvement in the control group.
Publication date / reference: 17/12/20. Zhu et al. Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China. PLoS One.
Summary: This multicenter retrospective cohort study in China examined four hundred and thirty-two COVID-19 survivors who were admitted between January 18 and March 15 2020. Outcomes were disability and anxiety. Limitations in instrumental activities of daily living (IADL) were assessed. Anxiety was evaluated using the Zung’s self-reported anxiety Scale. One or more IADL limitations was found in 36.81% of patients and severe ADL dependence in 5.56%. Severity of disease was significantly associated with greater ADL dependence. Anxiety was reported in 28.70% of those sampled and was also significantly associated with disease severity. The authors concluded that a significant proportion of COVID-19 survivors has disability and anxiety at discharge from hospital.
Publication date / reference: 10/12/2020 Howard et al. Prompt Use of Benzodiazepines for Anxiety Management in COVID-19–Positive Patients With Tracheostomy. Prim Care Companion CNS Disord.
Summary: In this small (n = 3) cases series, the authors attempt to add to the limited literature on the use of benzodiazepines in patients with anxiety who required tracheostomy as a result of COVID-19. Their cases report on the successful use of regular benzodiazepines in such patients, despite the theoretical risk of respiratory depression. They recommend clinicians consider the prompt use of benzodiazepines in order to decrease the risk of sequelae from subsequent anxiety.
Publication date / reference: 08/12/2020 Horn et al. Is COVID-19 Associated With Posttraumatic Stress Disorder? J Clin Psychiatry
Summary: This study examined patients presenting to a hospital in Lille with a confirmed diagnosis of COVID-19. Of the total, 70% were hospitalised, and 30% of the total had an ITU admission. Three weeks after the positive test, participants were given the impact of Event Scale-6 items to measure psychological distress. One month later, they were evaluated for PTSD using the PTSD Checklist for DSM-5 (PCL-5). A third of patients (33.5%) exhibited significant psychological distress, and this was a predictor for subsequent development of PTSD, as was ITU admission. The rate of PTSD was 6.5%.
Publication date / reference: 30/11/20. Luykx et al. Are psychiatric disorders risk factors for COVID-19 susceptibility and severity? a two-sample, bidirectional, univariable and multivariable Mendelian Randomization study. MedRxiv (pre-print, not peer-reviewed)
Summary: There have been several large-scale population studies that investigated bidirectional associations between COVID-19 and psychiatric disorders (as reported in this blog: Taquet et al.). In this pre-print (not peer-reviewed), Luykx et al. used multivariable Mendelian Randomisation (MR) to interrogate data from GWAS and investigate whether COVID-19 increases susceptibility to new onset psychiatric disorders or whether psychiatric disorders constitute a risk factor for developing COVID-19/worsening severity of COVID-19. The authors used GWAS data that incorporated a range of psychiatric disorders and the extensive COVID-19 Host Genetics Initiative. The MR analysis indicated that genetic liability to bipolar disorder slightly increased susceptibility to COVID-19 and COVID-19 severity (small overall effect size, OR=1.293). This perhaps relates to increased impulsivity and risky behaviours in this patient group and possibly warrants additional clinical caution for patients with bipolar disorder. Interestingly, in contrast to other studies there was no evidence that COVID-19 increased risk of developing psychiatric disorder. This lack of replication requires further exploration.
Publication date / reference: 28/11/20. Poyraz et al. Psychiatric morbidity and protracted symptoms after COVID-19. Psychiatry Res.
Summary: In this cross sectional single center survey study, Poyraz and colleagues investigated the prevalence of psychiatric symptoms in patients who have recovered from acute COVID-19 infection (N= 284). The survey screened for symptoms of PTSD (IES-R), anxiety and depression (HADS), sleep impairment (PSQI) and suicidality (Mini suicidality scale) among others. The authors found that a third (34.5%) of the patients reported clinically significant symptoms of PTSD, anxiety, and/or depression after a mean of 50 days post recovery from COVID-19. And a significant proportion (44%) of these patients continued to suffer from protracted symptoms (fatigue, headache, alteration of smell/taste, impaired concentration, daytime sleepiness). Notably, PTSD symptom severity was found to be the sole independent predictor of protracted COVID-19 symptoms. The findings of this study are limited by the convenience sampling and self-report survey method, but it nonetheless highlights that a significant proportion of patients suffer from protracted physical and psychiatry symptoms ‘recovery’ from COVID-19, and suggests a significant inter-relationship between the two that warrants further research examination.
Publication date / reference: 12/11/2020 Janiri et al. Psychological Distress After Covid-19 Recovery: Reciprocal Effects With Temperament and Emotional Dysregulation. An Exploratory Study of Patients Over 60 Years of Age Assessed in a Post-acute Care Service. Front. Psychiatry
Summary: In this study Janiri et al. reported on the long-term psychological effects of COVID-19. Psychological distress; Kessler questionnaire K10), affective temperaments (39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego; TEMPS-A-39) and emotional dysregulation (Difficulties in Emotion Regulation Scale; DERS) were assessed in 61 patients (≥60 years of age. High likelihood of psychological distress was associated with female gender, cyclothymic and depressive temperament, lack of impulse control and lack of clarity.
Publication date / reference: 24/12/20 Şahan et al. Can we predict who will be more anxious and depressed in the COVID-19 ward? J Psychosom Res.
Summary: In this cross-sectional study Sahan et al. explored the prevalence of anxiety and depression in 281 hospitalised patients with COVID-19. Following a telepsychiatric assessment to evaluate mood, anxiety and suicidal thoughts, the Hospital Anxiety and Depression Scale (HADS) was administered. Significant levels of anxiety were observed in 98 patients (34.9%) and significant levels of depression in 118 (42.0%). Staying alone in a hospital room was associated both with anxiety and depression. Anxiety was also associated with female gender, being in the beginning of hospital stay and history of psychiatric disorder, while depression was associated with age over 50 years and NSAID use the week before hospital admission.
Publication date / reference: Dec 2020. Sahoo et al. Psychological experience of patients admitted with SARS-CoV-2 infection. Asian J Psychiatr.
Summary: This retrospective cohort study assessed 50 patients on their experience of being admitted to a COVID-19 isolation ward or ICU. They found that the majority of patients display a wide range of unpleasant emotions potentially fuelled by media but in particular anxiety, isolation and remaining worried. They also found that over time patients become more familiar with their surroundings and become more relaxed as the hospital stay goes on and their faith in human relationships is strengthened. They also state that despite adequate psychological support just under two fifths of patients still score for anxiety and/or depression near discharge.
Publication date / reference: Dec 2020. He et al. Prevalence of anxiety and depression symptoms in the Chinese population in relation to exposure to COVID-19 and region of residence. Asian J Psychiatr.
Summary: The authors of this prospective observational study sought to elucidate the prevalence of anxiety and depression in a Chinese population (n=7143) stratified by those with confirmed COVID-19, or by high or low risk of COVID-19 exposure. Based on the Zung self-report depression scale and self-report anxiety scale, the infected group (n=318) reported the highest prevalence of severe depression (48 %) and severe anxiety (53 %). Univariate regression analysis demonstrated that patients with confirmed COVID-19 were at greater risk of having severe anxiety and depression, compared to participants who were at low risk of COVID-19 exposure. This held true after controlling for gender, age, residence, and educational background. In this brief report, the authors did not describe the severity of COVID-19 illness or the duration from acute COVID-19 illness to the self-reporting of symptoms.
Publication date / reference: Dec 2020. Chieffo et al. Psychopathological profile in COVID-19 patients including healthcare workers: the implications. Eur Rev Med Pharmacol Sci.
Summary: This prospective cohort study aimed to assess the psychological impact of COVID-19 hospitalisation between healthcare workers (HCW) (n=8) and non-HCW (n=26). HCW showed significantly more levels of self-reported distress at four months follow-up (p=.015). At follow-up HCW also reported more anxiety symptoms (p=.019) leading the authors to suggest the implementation of specialist post-traumatic psychological services for HCW hospitalised by COVID-19.
Publication date / reference: 20/11/20 Xiao et al. Effects of progressive muscle relaxation training on negative emotions and sleep quality in COVID-19 patients: A clinical observational study. Medicine (Baltimore).
Summary: This study assessed the effects of progressive muscle relaxation therapy on 39 inpatients with COVID-19 and compared outcomes with 40 COVID-19 inpatient controls who only received routine treatment and nursing. After intervention, significant differences in scores on Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) were observed.
Publication date / reference: 10/10/2020. Parker et al. Depression, Anxiety, and Acute Stress Disorder Among Patients Hospitalized With Coronavirus Disease 2019: A Prospective Cohort Study. psychosomatics .
Summary: Cross sectional study point prevalence of psychiatric symptoms in non-ICU treated COVID-19 inpatients (N=58). Of those 36% of subjects showed elevated anxiety symptoms (HADS-A), 29% showed elevated depressive symptoms (HADS-D). At two week follow-up, 9% had elevated anxiety symptoms, 20% had elevated depression symptoms and 25% had mild to moderate acute stress disorder symptoms, discharge home was not associated with improvement in psychiatric symptoms. Of note, patients presented with derium were excluded from the study due to difficulty obtaining consent. The finds are further limited by the small sample size.
Publication date / reference: 13/11/2020 Van Der Meer et al., Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: findings from a population-based study – ERRATUM. BJPsych Open
Summary: This was a retrospective population-based study looking at n=632 COVID-19 positive patients and ascertain any association with prior. Psychiatric disorders. Their results suggest that although those with a background of psychiatry disorders were tested more, the results were often negative. The authors found that of those who had a positive test, 344 (23.3%) had a previous psychiatric disorder and 187 (12.7%) had a background of a neurological disorder. More specifically, 156 (10.6%) had depression, 173 (11.7%) had a background of substance use and 80 (5.4%) had anxiety. They found that certain psychiatric conditions were less prevalent in those that were tested positive such as substance abuse (p= 0.0002).
Publication Date/ Reference: 2/11/2020. Konstantinos N Fountoulakis et al. Self-reported changes in anxiety, depression and suicidality during the COVID-19 lockdown in Greece. J Affect Disord.
Summary: This study used an online questionnaire to evaluate changes in anxiety, depression and suicidality during the COVID-19 lockdown in Greece. Data from 3399 individuals was used, and clinical depression was identified in 9.31%, while 8.5% had severe distress. There was an increase in suicidal thoughts in 10.40% of the sample, and a decrease in 4.42%. The authors created a model explaining the development of depression with several factors considered such as general health status, previous history of depression, self-harm and suicidal attempts, family responsibility. They also considered economic change, and age acting as risk factors, while keeping a daily routine, pursuing religiousness/spirituality, and believing in conspiracy theories acting as protective factors. The authors concluded that their model revealed an interplay leading from anxiety to clinical depression to suicidality through distress. As most of the factors in the model are modifiable, they recommend that future research and interventions should focus on them.
Publication Date/ Reference: 12/11/2020. Sensoy et al. Anxiety and depression levels in Covid-19 disease and their relation to hypertension. Clin Exp Hypertens.
Summary: Cross sectional study of 91 patients with confirmed (N=31) or suspected (N=30 inpatient, N=30 outpatient) COVID-19 patients, their anxiety (Beck Anxiety Inventory) and Depressive state (Beck Depression Inventory). Study found a higher than average incidence of depression (24%) and anxiety (44%) in this cohort of patients. Level of anxiety was also found to be higher in inpatients compared to outpatients, as well as independently associated with hypertension. Result of the study is limited by the small sample size.
Publication date / reference: 09/11/2020 Taquet et al. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psych.
Summary: In this large retrospective cohort, which has previously been featured on this blog as a preprint, the authors analysed a large cohort (>62k) of patients. A) COVID-19 was associated with subsequent psychiatric morbidity, some of it new-onset: the incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18%, including 6% that were a first diagnosis; incidence of a first diagnosis of dementia in the same time period after COVID-19 diagnosis was 2% (in people older than 65 years). Not only that, but patients with a pre-existing psychiatric diagnosis had a higher incidence of COVID-19 diagnosis (RR 1.65). The authors state that thiis risk was independent of known physical health risk factors for COVID-19, but that they could not exclude possible residual confounding by socioeconomic factors.
Publication date / reference: 04/11/20 Sönmez Güngör et al. Adverse drug reactions associated with concurrent acute psychiatric treatment and COVID-19 drug therapy. Int J Psychiatry Clin Pract.
Summary: The authors of this study report on adverse effects of drug therapy observed in 23 patients with COVID-19 who had been admitted to an acute psychiatric clinic. 4 out of 23 patients experienced adverse effects, with two having mild hepatic enzyme elevation and one mild sinus bradycardia. Adverse effects were not significantly associated with patient-related factors nor dose of antipsychotic medication.
Summary: In their publication Jiang et al. report the results of two cross-sectional investigations, conducted in February and March 2020. The prevalence and severity of depression and anxiety, as well as sleep quality in 202 patients with COVID-19 were evaluated with Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). The study also explores the association between different demographic characteristics of the sample and mental health status.
Publication Date/ Reference: 30/11/2020 Kim et al. Telephone based Interventions for Psychological Problems in Hospital Isolated Patients with COVID-19. Clin Psychopharmacol Neurosci.
Summary: This single-center study evaluated the usefulness of telephone based interventions by psychiatrists to 33 hospitalised COVID-19 patients. Psychological interventions were delivered via phone for approximately 30 minutes twice a week for a maximum of 5 sessions. Of enrolled patients, clinically meaningful psychological symptoms were found in 6 for anxiety, 13 for depression, 10 for insomnia and 3 for suicidal ideation. The telephone interventions were supplemented by psychotropic medication in 9 participants. Significant improvements for anxiety, depression, and suicidal ideation were found at one week but not two weeks when compared to baseline. This is a relatively small sample size with significant heterogeneity in the psychological problems of COVID-19 patients targeted so should be taken with caution. It does however raise the importance of evaluating the effectiveness of telephone-based interventions to treat psychological complications of COVID-19 infections through larger scale and randomised control trials.
Publication Date/Reference: 26/10/20 Benedetti et al. Can Cytokine Blocking Prevent Depression in COVID-19 Survivors? J Neuroimmune Pharmacol.
Summary: This prospective surveillance study assessed depressive symptoms and PTSD in 84 males who were hospitalised and survived COVID-19. They compared standard treatment against standard treatment plus cytokine-blocking agents (Anakinra or Tocilizumab) on inflammatory markers and self reported psychopathological status. They found that cytokine-blocking agents were protective of depressive symptoms at three month follow up but not PTSD.
Publication Date/Reference: 06/10/2020 Samrah et al. Depression and Coping Among COVID-19-Infected Individuals After 10 Days of Mandatory in-Hospital Quarantine, Irbid, Jordan. Psychol Res Behav Manag.
Summary: In this cross-sectional study of patients admitted to a hospital in Jordan with covid-19, the authors used the PHQ-9 to screen for symptoms of depression. They found that 21% were at ‘high-risk’ of depression (PHQ-9 score ≥10). This is a moderately high prevalence, but it is worth bearing in mind that in Jordan any patients with confirmed covid-19, even if they are asymptomatic, are required by law to be detained in hospital; this clearly introduces a substantial cofounder.
Publication date / reference: 22/10/20. Fond et al. Disparities in Intensive Care Unit Admission and Mortality Among Patients With Schizophrenia and COVID-19: A National Cohort Study. Schizophr Bull.
Summary: This population-based cohort study in France examined all patients admitted with COVID-19 who were hospitalised (n=50,750) between February and June 2020. Cases were patients with a diagnosis of schizophrenia. Controls were patients without a diagnosis of severe mental illness. The outcomes studied included in-hospital mortality and intensive care admission. 823 cases were included; patients with schizophrenia had increased in-hospital mortality (25.6% vs 21.7%; adjusted OR 1.30 [95% CI, 1.08-1.56], p=0.0093) and a decreased ICU admission rate (23.7% vs 28.4%; adjusted OR 0.75 [95%CI, 0.62-0.91], p=0.0062) compared with controls. Significant interactions between schizophrenia and age for mortality and ICU admission were observed (p=0.0006 and p<0.0001). Patients with schizophrenia between the ages of 65 and 80 years had a significantly higher risk of death than controls of the same age (+7.89%) and those younger than 55 years had more ICU admissions (+13.93%). The authors highlighted the disparities in health and health care between patients with schizophrenia and individuals without a diagnosis of severe mental illness. They concluded that age and clinical profile was an important factor in the disparities, suggesting that personalised management of COVID-19 in such cases is of importance.
Publication date / reference: 22/10/2020 Jaworowski et al. Three Cases of COVID-19-related First Onset Brief Reactive Psychosis. Isr Med Assoc J.
Summary: This is a case series of three men with COVID-19 who developed transient new onset psychotic symptoms while infected which resolved within 2 days. All had mild respiratory symptoms, had religious and grandiose delusions and were treated with neuroleptic medications. The authors argue that as all patients had mild symptoms and were not recieving steroids their symptoms are most likely caused by non-organic brief psychotic disorder induced by situational stress related to the COVID-19 pandemic
Publication date / reference: 02/10/20. Xie et al. COVID-19 patients managed in psychiatric inpatient settings due to first-episode mental disorders in Wuhan, China: clinical characteristics, treatments, outcomes, and our experiences. Transl Psychiatry.
Summary: The authors of this study compared 25 COVID-19 patients with first-onset mental disorders and 55 controls with first-onset mental disorders. In COVID-19 patients adjustment disorder and acute and transient psychotic disorders were most common, whilst schizophrenia and alcohol use disorders were most common amongst controls. Insomnia symptoms, aggressive behaviours and delusion were common in COVID-19 patients, and length of stay was significantly shorter in the COVID-19 group compared to controls.
Publication date / reference: 30/09/20. Chang and Park. Incidence of post-traumatic stress disorder after coronavirus disease. Healthcare (Basel).
Summary: The authors of this study followed-up 64 COVID-19 patients discharged from hospital between February and April 2020 and evaluated them with the Post-Traumatic Stress Disorder Checklist-5. They found that 13 participants had a score of >33 thus indicating a 20.3% prevlaance of PTSD, and no significant differences in sex, age, hospitalisation time and duration post-discharge were seen between those with or without PTSD.
Publication date / reference: 14/09/20. Liguori et al. Depressive and anxiety symptoms in patients with SARS-CoV2 infection. J Affect Disord.
Summary: Prospective study in 103 patients with COVID-19, in which anxiety symptoms were reported by 34/103 patients and depressive symptoms by 39/103. No information is given about how these symptoms were identified other than “by an anamnestic (history) interview requiring a ‘yes/no’ decision”. The prevalence figures were reported previously here. This secondary analysis adds detail including that depressive symptoms associated with higher CRP, more concomitant neurological symptoms, higher anxiety, and more reports of muscle ache.
Publication date / reference: 26/08/20. Yan et al. Neurological Implications of Non-critically Ill Patients With Coronavirus Disease 2019 in a Fangcang Shelter Hospital in Wuhan, China. Front Neurol.
Summary: This retrospective cohort study assessed the neurological manifestations of 1,682 patients with confirmed non-critically ill COVID-19 seen consecutively in a single shelter hospital in China. Critically unwell patients with organ failure, shock or needed ventilation were not admitted to the facility. Of these patients 30% had neurological symptoms, with myalgia (18.5%), headache (12.8%) and fatigue (4.9%) most commonly seen. Those with neurological symptoms had significantly longer admissions and significantly higher rates of respiratory symptoms.
Publication date / reference: 24/08/2020 Yang et al. Social support and clinical improvement in COVID-19 positive patients in China. Nurs Outlook.
Summary: Study of 35 patients with COVID-19. In total, 32 exhibited sleep, depressive and anxiety symptoms which improved post support intervention.
Publication Date/ Reference: 19/09/20. Ojeahere et al. Management of psychiatric conditions and delirium during the COVID-19 pandemic across continents: The lessons thus far. Brain Behav Immun Health.
Summary: Working within the World Psychiatry Association the authors surveyed 21 early-career psychiatrists on five continents about local insights on the management of delirium and other psychiatric conditions manifesting in patients with COVID-19. Consensus (“>70% representative agreeable”) was taken as a “modified Delphi method”. The authors reported country-specific insights from Germany, Iran, Kosovo, Lebanon, Nigeria, Thailand, Tunisia, Turkey, and the USA. The result is a very interesting narrative, even if it is difficult to draw conclusions beyond generalities.
Publication date / reference: 07/10/20. Wang et al. Increased risk of COVID-19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States. World Psychiatry.
Summary: Wang et al. examined the impact of mental disorders on the risk of COVID‐19 infection, using electronic health records from 360 hospitals and 317,000 providers across 50 states in the US. In over 60M adult patients, 11.2M had a lifetime diagnosis of a mental disorder and 1.3M had a recent diagnosis (within the past year), and 15110 patients had a diagnosis of COVID-19. After adjusting for age, gender, ethnicity, and medical comorbidities, patients with a recent diagnosis of a mental disorder had significantly higher odds of COVID‐19 infection than patients without a mental disorder. The strongest effects were seen for depression (OR=7.6), schizophrenia (OR=7.3), ADHD (OR=5.8), and bipolar disorder (OR=5.7). Among the 3,430 adults with both COVID‐19 and a recent diagnosis of a mental disorder, 290 (8.5%) died, with no evidence of differential effects by ethnicity. The authors speculated that the higher frequency of COVID-19 infection in people with mental disorders may be attributable to difficulty appraising health information and complying with preventive behaviors, or socioeconomic disadvantage. Apart from the limitations of correlational data the authors acknowledged that patient electronic health records have limited information on socioeconomic and lifestyle determinants, and are likely to have missed many cases of COVID-19 – particularly asymptomatic ones. However the study is consistent with a growing body of literature identifying mental disorders as a health risk factor for COVID‐19 infection.
Publication date / reference: 18/09/20. Chen et al. Investigation of the psychological status of suspected patients during the Coronavirus disease 2019 epidemic. Medicine (Baltimore).
Summary: The authors measured psychological symptoms in 31 patients suspected to have COVID-19 and admitted to hospital in Jan-Feb 2020. Using the PHQ-9 and GAD7 they found 10/31 patients reported symptoms of depression, eight of which were mild in severity. Similarly among the six patients with elevated anxiety, half were mild in severity.
Publication date / reference: Aug 2020. Zhang et al. A psychological investigation of coronavirus disease 2019 (COVID-19) patients in mobile cabin hospitals in Wuhan. Ann Transl Med.
Publication date / reference: 17/09/20. Pinnetti et al. SARS-CoV-2 infection does not induce HIV viral escape in Central Nervous System: a case series. Int J Infect Dis.
Publication date / reference: 13/09/20. Butler et al. Clozapine prescribing in COVID-19 positive medical inpatients: a case series. Ther Adv Psychopharm.
Summary: The authors report on their experiences of clozapine in COVID-19 positive patients who were admitted to medical hospital, some of whom were sufficiently unwell with COVID-19 pneumonia to require intensive care admission. Their data did not indicate worse outcomes for patients who received clozapine (one patient relapsed after it was held). Although previous larger studies have addressed risk of contracting COVID-19 in clozapine patients, this study was one of the first to address outcomes. Study limitations include the small size, retrospective design, and short follow-up period.
Publication date / reference: 10/09/20. Iqbal et al. Psychiatric presentation of patients with acute SARS-CoV-2 infection: a retrospective review of 50 consecutive patients seen by a consultation-liaison psychiatry team. BJPsych Open.
Summary: In this retrospective case note review, the authors characterised the psychiatric morbidity associated with confirmed SARS-CoV-2 infection in 50 consecutive adult patients referred to a consultation-liaison psychiatry service in Qatar. Most of the referrals had mild symptoms, or no symptoms, of COVID-19. Over three hospital sites in Doha the authors most commonly identified delirium, non-affective psychosis, acute stress reaction, anxiety disorder, mania, or depression. One-third of the patients had a past psychiatric history including eight with a history of psychosis or bipolar I disorder who all presented with a relapse in the context of COVID-19 infection. Conversely however, approximately half of the patients presenting with mania or non-affective psychosis had no past psychiatric history: their first episode of illness coincided with being positive for SARS-CoV-2. The authors concede that the quality of a retrospective case-note review depends on the quality of the medical notes, and that neuropsychiatric cases of a more neurological flavour may have been referred to neurology rather than to psychiatry. However the study provides a broad clinical overview of liaison psychiatric problems associated with acute SARS-CoV-2 infection in a general hospital setting, including patients who were asymptomatic for COVID-19 infection.
Publication date / reference: 28/08/20. Dai et al. Anxiety and depressive symptoms among COVID-19 patients in Jianghan Fangcang Shelter Hospital in Wuhan, China. PLoS One.
Summary: In this prospective study, Dai and colleagues collected questionnaire data on anxiety and depressive symptoms in patients with COVID-19 who were admitted to a shelter hospital in Wuhan, China (n=307; unclear if PCR). The prevalence of anxiety and depressive symptoms were 18.6% and 13.4%, respectively. The authors explored risk factors associated with symptoms of psychological distress. Poor sleep quality and having greater than two current physical symptoms were independent risk factors for anxiety symptoms. Whereas, female sex, having a family member with confirmed COVID-19, and having ≥ two current physical symptoms were independent risk factors for depressive symptoms. These preliminary findings may assist in detecting which patients with COVID-19 are at greatest risk of developing adverse psychological symptoms.
Publication date / reference: 14/06/20. Ramezani et al. The Role of Anxiety and Cortisol in Outcomes of Patients With Covid-19. Basic Clin Neurosci.
Summary: Cross-sectional study evaluating correlations between distress, serum cortisol and outcome in 30 patients with confirmed, mild-to-moderate COVID-19. HADS score correlated positively with cortisol level on the day of admission, and higher values of both variables associated with mortality. The authors hypothesised that stress and anxiety may increase the impact of an already-established infection. The hypothesis is interesting, but the study is small, did not specify whether cortisol was drawn at the same time of day for all patients (perhaps unlikely, if taken on the day of admission), and did not report longitudinal data.
Publication date / reference: 14/08/20. Wesemann et al. Influence of COVID-19 on General Stress and Posttraumatic Stress Symptoms Among Hospitalized high-risk Patients. Psychol Med.
Summary: This study aimed to determine the prevalence of “general stress” and post-traumatic stress in 60 patients hospitalised with suspected (n=41) or confirmed (n=19) COVID-19. Following hospital admission, all COVID-19 suspected patients were provided with the PTSD checklist for DSM-5 and the PHQ stress module. The prevalence of significant post-traumatic stress symptoms was 37.9% (96% CI: 35.5-40.3%) in all patients and 42.1% (95% CI: 37.2-47.0%) in the subgroup of patients with confirmed SARS-CoV-2 infection. There was no significant difference in severity of symptoms between groups. There was, however, a significant correlation between the diagnosis of COVID-19 and the stress module of the PHQ. The authors urged regular screening for mental fitness in COVID-19 patients.
Publication date / reference: 09/08/20. Huarcaya-Victoria et al. Psychotic symptoms in COVID-19: a case series from Lima, Peru. Psychiatry Res.
Summary: The authors of this case series reported three cases of psychosis in patients with recently diagnosed COVID-19. They appreciated that a direct causal relationship between SARS-CoV-2 and the development of psychotic symptoms was not established, and postulated that in these cases the psychosis may be explained by different pathogenic mechanisms including neuroinvasion, systemic inflammatory processes and psychosocial response to isolation and life changes during the pandemic.
Publication date / reference: 16/08/20. Taquet et al. Bidirectional associations between COVID-19 and psychiatric disorder: a study of 62,354 COVID-19 cases. MedRxiv.
Summary: The authors asked two questions. First, what is the incidence of a clinical psychiatric diagnosis following infection with the virus, and second, does pre-existing psychiatric disorder affect susceptibility to COVID-19 infection? They interrogated the TriNetX database and found that in 44 779 patients with no prior psychiatric history, COVID-19 was associated with a significantly increased incidence of a novel psychiatric diagnosis in the three months after infection, compared to six other health events. The probability of any new-onset clinical psychiatric illness following COVID-19 was 5.8%. Meanwhile in 1,729,837 matched patient-control pairs, having any psychiatric diagnosis in the previous year was associated with a 65% higher relative risk of COVID-19 independently of known physical health risk factors for COVID-19. The authors call for adequate service provision in anticipation of an increased incidence of psychiatric illness following COVID-19, perhaps with proactive psychiatric follow up among survivors of COVID-19, and for detailed investigation of the impact on COVID-19 on incident dementia.
Publication date / reference: 21/07/20 Kotabagi et al. COVID-19 positive mothers are not more anxious or depressed than non COVID pregnant women during the pandemic: A pilot case-control comparison. Eur J Obstet Gynecol Reprod Biol.
Summary: a follow up study to Kotabagi et al. reporting no significant differences in median GAD-9 and PHQ-9 measures for anxiety and depression respectively in groups of mothers with SARS-CoV-2 (n=14) and without (n=14). As they had previously shown, the scores on the measures rose to a peak at the height of the pandemic deaths and lockdown introduction but waned when more information was released regarding maternal and foetal health outcomes in SARS-CoV-2 infection.
Summary: This retrospective cohort study aimed to evaluate psychological distress and its correlates in a population of COVID-19 survivors (n=126) who were recently discharged from hospital and were in quarantine at a government facility. Participants were given a questionnaire including PTSD, anxiety and depression rating scales. The authors found that nine (31.0%), 28 (22.2%), and 48 (38.1%) of the patients met the cut-score for clinical significant symptoms of stress response, anxiety, and depression, respectively. Potential correlates of these measures included infected family members and postinfection physical discomfort. Interestingly, patients above the age of 60 experienced less severe stress response symptoms, fewer emotional symptoms of depression, and fewer anxiety symptoms than younger patients, which could indicate that younger people are more at risk of emotional distress following COVID-19.
Publication date / reference: Preprint. Hoertol et al. Association between SSRI Antidepressant Use and Reduced Risk of Intubation or Death in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study. MedRxiv Preprint.
Summary: In this multicentre observational retrospective study, the authors examined associations between the use of antidepressants in patients with COVID-19 and endpoints of intubation or death. A total 7,345 patients were included in the analysis, of whom 460 received an antidepressant during hospitalisation, at a mean fluoxetine-equivalent dose of 21.4mg per day. In patients exposed to any antidepressant the primary endpoint of intubation or death occurred in 143 patients (31.1%), whereas in non-exposed patients, 1,188 (17.3%) had this outcome. Unadjusted hazard ratio estimates of the association between antidepressant use and the primary outcome stratified by age were non-significant, except in the 71-80 years group, where antidepressant use was significantly associated with lower risk of intubation or death (HR=0.66, SE=0.20, p=0.041). After adjustment for older age and the greater medical severity of patients receiving antidepressants than those not, a significant association was found between any antidepressant use and reduced risk of intubation or death (HR=0.64, 95% CI 0.51-0.80, p<0.001). The authors concluded that use of antidepressants is associated with a substantial reduced risk of death or intubation.
Publication date / reference: 29/07/20 Mazza et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun.
Summary: Prospective cross-sectional analysis of depressive, anxious, obsessive, and post-traumatic symptoms among 402 survivors assessed one month post-hospital treatment. The authors found a high prevalence of psychopathology: more than half of patients scored above threshold in at least one instrument, and one in five scored highly in at least three. Female sex and a postive past psychiatric history independently predicted worse emotional states. The authors conclude that there may be a high prevalence of psychiatric sequelae post COVID-19.
Publication date / reference: 27/07/20 Govind et al. Clozapine treatment and risk of COVID-19. Br J Psychiatry.
Summary: This retrospective cohort study identified 6,309 individuals with schizophrenia-spectrum diagnoses taking antipsychotic medications within South London and Maudsley NHS Foundation Trust. Those taking clozapine were compared with those prescribed any other antipsychotics for risk of contracting COVID-19 during the pandemic. 1.62% of the cohort tested positive for SARS-CoV-2 infection and 20.32% were prescribed clozapine. A hazard ratio of 2.62 (95% CI 1.73 – 3.96) was reported for patients receiving clozapine who were SARS-CoV-2 positive which increased to 3.06 (95% CI 2.01 – 4.67) following adjustment for sociodemographic factors. However, after accounting for inpatient contact, BMI and smoking status, it reduced to 1.76 (95% CI 1.14 – 2.72). Despite a relatively small cohort, the authors thus concluded that receiving clozapine treatment may be associated with an increased risk of developing COVID-19.
Publication date / reference: 28/07/20 Silva et al. Clozapine and COVID-19. BJPsych Bulletin.
Summary: A correspondence piece outlining the risks and challenges posed by COVID-19 for initiating and managing individuals on clozapine. The authors highlight the overlap between COVID-19 symptoms and side-effects of clozapine, calling for cautious interpretation of abnormal laboratory tests as part of clinical evaluation. In particular, they highlight that acute-phase reaction in individuals with COVID-19 may result in reduced enzyme activity, raising clozapine levels and necessitating further investigations and dose adjustments if indicated. They also discuss modifications to routine blood test monitoring and clozapine clinics. The authors conclude that the risks of COVID-19 are insufficient to justify stopping clozapine.
Publication date / reference: 08/07/20 Chen et al. Predictors of Health-Related Quality of Life and Influencing Factors for COVID-19 Patients, a Follow-Up at One Month. Front Psychiatry.
Summary: Multi-centre, prospective cross-sectional study of the health-related quality of life (HRQoL) of 361 Chinese confirmed COVID-19 patients, measured one month following hospital discharge. A high majority of participants (90.6%) had mild disease and the remainder had severe disease. Using the SF-36 questionnaire and compared to Chinese population norms, patients reported poorer role functioning due to physical or emotional problems, and poorer social functioning; but also less pain and better general and mental health. Notwithstanding this conflict, patients with severe disease consistently reported worse QOL.
Publication date / reference: 23/07/20 Zhang et al. The relationship between resilience, anxiety, and depression among patients with mild symptoms of COVID-19 in China: A cross-sectional study. J Clin Nurs.
Summary: In this cross sectional survey study (n=299), the relationship between resilience (Chinese version of the Connor-Davidson Resilience Scale) and anxiety and depression (HADS) was investigated in patients with mild symptoms of COVID-19. The investigators found that resilience correlated inversely with anxiety and depression. The study is limited by the convenience sampling method, cross sectional study design but implies one reason why some patients may cope better with the uncertainty of infection than others.
Publication date / reference: 13/07/20 Liu et al. Risk factors associated with mental illness in hospital discharged patients infected with COVID-19 in Wuhan, China. Psychiatry Res.
Summary: This study utilised a cross-sectional survey (n=657) to explore the risk factors associated with mental health problems among discharged COVID-19 patients. A brief discrimination scale was used to determine personal attitudes following discharge as well as Chinese versions of validated measurement tools such as the GAD-7 and PHQ-9 (cut-offs of 5 for ‘mild’ anxiety and depression). 12.4% of respondents had clinically significant symptoms of PTSD. For anxiety, 10.4% were categorised as having moderate to severe symptoms, and 32.3% had mild symptoms. Median scores on the GAD-7 and PHQ-9 were 4 and 7, respectively. The odds of reporting moderate to severe anxiety were 2.91 times more likely with higher disease severity. Interestingly, perceived discrimination was ranked as the most important predictor of anxiety, depression and PTSD. The authors stated that their sample is representative of the general Chinese population, but noted causal inference is limited by the study design.
Publication date / reference: 19/05/20 Boland & Dratcu. Clozapine in the time of COVID-19. Clin Psychopharmacol Neurosci.
Summary: The authors report on two patients with treatment resistant schizophrenia who required psychiatric admission during the COVID-19 pandemic and who were treated with clozapine. One tested positive for SARS-CoV-2; the other tested negative but had contact with COVID-19 during initiation of clozapine treatment. Both responded well and were safely discharged from hospital without any complication.
Publication date / reference: 15/07/20 Hu et al. Factors related to mental health of inpatients with COVID-19 in Wuhan, China. Brain Behav Immun.
Summary: The authors report a cross-sectional questionnaire survey conducted in 85 Chinese inpatients with definite COVID-19 in two isolation wards of a Wuhan hospital. There was a reportedly high prevalence of depressive symptomatology (39/85 score 5+ on PHQ-9), anxiety (33/85 score 5+ on GAD-7), and insomnia (46/85 score 8+ on the Insomnia Severity Index). Like others, the questionnaire thresholds here are on the low side and in the case of the PHQ-9, very low indeed. Future papers should present frequencies arising from different thresholds for ‘caseness’ – or even better conduct clinical interviews to determine the presence or absence of neuropsychiatric disorder.
Publication date / reference: 16/07/20 Gee & Taylor. The effect of COVID-19 on absolute neutrophil counts in patients taking clozapine. Ther Adv Psychopharmacology.
Summary: The authors reviewed the neutrophil counts of thirteen patients admitted who were prescribed clozapine and developed confirmed COVID-19. There is currently uncertainty surrounding the use of clozapine in patients with COVID-19. Here the authors conclude that it is indeed safe to continue clozapine in COVID-19, and that neutropenia in COVID-19 patients taking clozapine should not be assumed to be a direct effect of the virus.
Publication date / reference: 07/07/20. Wu et al. Anxiety persists after recovery from acquired COVID-19 in anaesthesiologists. J Clin Anesth.
Summary: The authors hypothesized that anaesthetists who contracted COVID-19 might have a high prevalence of elevated anxiety, persisting after recovery. Using a survey design to identify anaesthetists with possible hospital-acquired COVID-19 (n=18, 14 of whom responded) they reported that most (n=11) did report ongoing mild anxiety after recovery.
Publication date / reference: 02/07/20. Ma et al. Prevalence of depression and its association with quality of life in clinically stable patients with COVID-19. J Affect Disord.
Summary: Using an online questionnaire survey design based in China, the authors propose a high prevalence of depressive symptoms of 43.1% (95%CI: 39.6%−46.6%) in adult patients with at least clinically likely COVID-19. The survey is notable for a very high reported response rate to invitation (770/784; 98.2% of those who were invited to participate returned questionnaires). However depressive symptoms were called using a PHQ-9 score of only five or more, which is very low when the usual threshold is ten. Individual patient data that would permit a sensitivity analysis at different PHQ-9 thresholds are not provided in the article.
Publication date / reference: 14/07/20. Nie et al. Anxiety and depression and its correlates in patients with coronavirus disease 2019 in Wuhan. Int J Psychiatry Clin Pract.
Summary: This single-centre cross-sectional study assessed self-reported depressive and anxiety symptoms (Zung self-rating depression scale [ZSDS] and Zung self-rating anxiety scale [ZSAS], respectively) in patients hospitalised with clinically confirmed COVID-19 (n=78). Twenty-eight patients scored above threshold for clinically significant depressive symptoms, mostly mild, and 30 likewise for anxiety. Therefore over one-third of COVID-19 patients reported distressing psychological symptoms. After adjusting for sex and education level, having a family member who either had, or who had died, from COVID-19 was independently associated with psychological outcomes.
Publication date / reference: 01/06/20. Anmella et al. COVID-19 inpatients with psychiatric disorders: Real-world clinical recommendations from an expert team in consultation-liaison psychiatry. J Affect Disord
Summary: The authors present three case-scenarios to demonstrate the challenges and best-practice recommendations of psychiatric comorbidity in COVID-19. Anmnella and colleagues make certain case-centered recommendations including psychopharmacological adaptations in patients receiving anti-retrovirals, appropriate prescribing in delirium and the importance of a personalised approach to treatment. Managing pharmacological interactions in this population can be challenging, the authors stress that when prescribing it is important to contextualise interaction risks, rather than seeing them as absolute.
Publication date / reference: 30/06/20 Li & Wang Prevalence and predictors of general psychiatric disorders and loneliness during COVID-19 in the United Kingdom. Psychiatry Res
Summary: This is a large scale (n=15530) cross sectional survey aimed to explore the prevalence and predictors of general psychiatric disorders (GHQ-12) and loneliness (adapted question from ELSA) in the UK during COVID-19 pandemic. The study found high prevalence rates of general psychiatric disorders (29.2%) and loneliness (35.86%). People with current or past symptoms of COVID-19 were significantly more likely to report general psychiatric disorders and to endorse loneliness. It is worth noting that the study used self-reported COVID-19-related symptoms instead of confirmed diagnoses. The authors argued that this method addressed the problem of delayed testing, and that suspected patients deserve scholarly attention regardless of confirmation.
Publication date / reference: Suwanwongse & Shabarek. Lithium toxicity in two Coronavirus Disease 2019 (COVID-19) patients. Cureus.
Summary: Two cases of psychiatric patients on lithium, presenting with some features consistent with lithium toxicity (primarily behavioural change and change in consciousness level), high Lithium levels on admission (both >2.2 mmol/L) with acute kidney injury, and PCR-confirmed SARS-CoV-2. Ataxia, nystagmus, and other neurological signs were not reported. The authors recommend that Lithium levels are obtained in all suspected COVID-19 patients who are currently taking lithium.
Publication date / reference: 05/07/20. Taylor et al. COVID Stress Syndrome: Concept, Structure, and Correlates. Depress Anxiety.
Summary: The authors further validated their previously-published COVID Stress Scales measuring five intercorrelated factors corresponding to a putative “COVID stress syndrome”: fear of its dangerousness; worry about socioeconomic costs; xenophobic fears that foreigners spread it; traumatic stress syndromes associated with direct or vicarious exposure; and compulsive checking and reassurance seeking. Popular coping strategies included phoning friends, cleaning, cooking, sleeping, shopping, eating, drinking, and “searching for porn on the internet”.
Publication date / reference: 09/07/20 Yahya & Khawaja COVID-19 and Perinatal Psychiatry. Prim Care Companion.
Summary: commentary piece making the case that COVID-19 pandemic will cause increase in perinatal mental disorder.
Publication date / reference: 02/07/20 Speth et al. Mood, anxiety and olfactory dysfunction in COVID-19: evidence of central nervous system involvement? Laryngoscope.
Summary: This prospective cross-sectional study examined anxiety and depressive symptoms in n=114 confirmed COVID-19 patients, using the GAD-2 and PHQ-2 respectively. Sinonasal symptoms were also assessed. The measures were completed for the present state (during infection) and retrospectively assessed for patients’ pre-COVID-19 baseline. Scores on both questionnaires were significantly higher during infection than at the recalled pre-COVID baseline. Psychiatric symptom severity associated positively with age and olfactory and gustatory dysfunction. The authors suggest that emotional disturbances may result from SARS-CoV-2 neuroinvasion. Key limitations include the use of ultra-short screening questionnaires and retrospective recall of “baseline” symptomatology.
Publication date / reference: 01/07/20 Paz et al. Anxiety and depression in patients with confirmed and suspected COVID-19 in Ecuador. Psychiatry Clin Neurosci.
Summary: Correspondence reporting the prevalence of depressive (PHQ-9) and anxiety (GAD7) symptoms in confirmed and suspected COVID-19 cases in Ecuador. Data were from Ecuadorian Ministry of Public Health’s COVID- 19 epidemiological surveillance program. N=759 completed the survey. The prevalence of depression was 22.9% in confirmed cases and 18.5% in suspected cases, and the prevalence of anxiety was 24.2% in confirmed cases and 21.4% in suspected cases.
Publication date / reference: 24/06/20 Parra et al. Psychotic symptoms in COVID-19 patients. A retrospective descriptive study. Psychiatry Res.
Summary: Retrospective case series of ten cases of first-onset psychotic symptoms in the background of COVID-19 infection (putatively excluding delirium). The psychosis was characterised by structured delusions mixed with confusional/attentional symptoms, meaning delirium was possibly not fully out of the picture, but interestingly the onset was nearly always >2 weeks following the debut of COVID-19 somatic symptoms.
Publication date / reference: 12/06/20 Chaumont et al. Mixed central and peripheral nervous system disorders in severe SARS-CoV-2 infection. J Neurol.
Summary: Case series (n=4) of extubated SARS-CoV-2 positive patients in ICU who demonstrated neuropsychiatric symptoms for the first time. These confusion, cognitive dysfunction, paranoid delusion & hallucinations as well as a range of neuropathies.
Publication date / reference: 11/06/20 Zarghami et al. A Report of the Telepsychiatric Evaluation of SARS-CoV-2 Patients. Telemed J E Health.
Summary: Single-centre prospective cohort study of n=82 SARS-CoV-2 patients assessed by videocall facility. The prevalence of mental disorder was 40%, with insomnia (29%) and adjustment disorder (16%) the most common individual syndromes. Patients who had been hospitalised were significantly more likely to have psychiatric disorder. The authors propose value in using telepsychiatry to help treat such patients.
Publication date / reference: 27/05/20 Caan et al. A Case of Catatonia in a Man with COVID-19. Psychosomatics.
Summary: First known case report of new onset catatonia in SARS-CoV-2 with no medical/psychiatric history. After numerous presentations to ED the patient developed psychotic symptoms and abnormal posturing. He had been treated with azithromycin for 5 days which authors highlight as possible contributing cause to presentation along with other medications prescribed. MRI brain was normal and symptoms seemingly responded to lorazepam.
Publication date / reference: 31/05/20 Kotabagi et al. Anxiety and Depression Levels Among Pregnant Women With COVID-19. Acta Obset Gynecol Scanda.
Summary: Cross sectional survey of SARS-CoV-2 expectant mothers (n=11). The authors highlighted heightened levels of stress and anxiety at the height of the lockdown, however reassuring these levels have tailed off as information about the prognosis of infected pregnant mothers has materialised.
Publication date / reference: 27/05/20 Palomar-Ciria et al. Schizophrenia and COVID-19 Delirium. Psychiatry Res.
Summary: Case report of a 65-year-old patient with stable schizophrenia. The patient was psychotic on presentation, but there were no respiratory symptoms. SARS-CoV-2 PCR was negative, but the patient was positive for IgG and IgM.
Publication date / reference: 21/05/20 French and Lyne. Acute exacerbation of OCD symptoms precipitated by media reports of COVID-19. Irish Journal of Psychological Medicine.
Summary: Case report of a lady in her thirties with contamination centred OCD. She presented with severe disablement stemming from a fear of contagion exacerbated by media reporting on the COVID-19 crisis. The case highlights some of the unseen dangers of media reporting on pandemics.
Publication date / reference: 18/05/20 Liu et al. Illness perception, mood state and disease-related knowledge level of COVID-19 family clusters, Hunan, China. Brain, Behaviour and Immunity
Summary: Novel study investigating the psychological disturbances seen in family clusters of SARS-CoV-2 infection. The authors document decreased confidence in healthcare and some mood disturbances in the cases compared to patients outside of cluster groups.
Publication date / reference: 18/05/20 Kajani et al. Neuroleptic Malignant Syndrome in a COVID-19 Patient. Brain, Behaviour and Immunity.
Summary: Case report of a middle-aged male with schizophrenia (haloperidol decanoate depot 3 weeks prior) who presented with fever, hypoxia and altered mental state. He had severe rigidity with a creatinine kinase of >120,000. This is the first known case report of NMS during an acute phase infection with SARS-CoV-2. The patient was intubated and placed on dantrolene infusion and at the time of writing his outcome was unknown. It is of note that haloperidol is likely to continue to lead to cases of NMS, with or without coincidental COVID-19 infection.
Publication date / reference: (date unknown) Hu W et al. COVID-19 outbreak increased risk of schizophrenia in aged adults. ChinaXiv (preprint)
Summary: 13,783 records from outpatients in January 2020 showed a positive relationship between incidence of schizophrenia in first-time patients and COVID-19 pandemic, particularly first presentations in those aged 39 – 50, which is unusual (♦).
Publication date / reference: 12/05/20 Iasevoli et al. Psychological distress in serious mental illness patients during the COVID-19 outbreak and one-month mass quarantine in Italy. Psychological Medicine.
Summary: this observational case-control analysis compares the impact of one month of COVID-19 lockdown on perceived stress, anxiety, depressive, and psychotic symptoms in patients with serious mental illness (n=205), their first-degree relatives (51), and non-psychiatric subjects. Unsurprisingly the cases scored more highly on these domains relating to pandemic related anxiety, the controls more surprisingly scored more highly on these domains than caregivers.
Publication date / reference: 08/05/20 Ovejero et al. Coronavirus infection as a novel delusional topic. Schiz Res.
Summary: Case report of a Spanish woman with bipolar disorder including SARS-CoV-2 infection in her delusions.
Publication date / reference: 07/05/20 Huarcaya-Victoria et al. Psychosis in a patient with anxiety related to COVID-19: A case report. Psych Res.
Summary: Case report of a 38-year-old woman who developed first onset psychosis with fixed beliefs on the SARS-CoV-19 pandemic(♦).
Publication date / reference: 20/04/20 Liu et al. Clinical characteristics of hospitalised patients with schizophrenia who were suspected to have coronavirus disease (COVID-19) in Hubei Province, China. General Psychiatry.
Summary: Comparison of psychiatric symptomatology between a group of isolated patients with schizophrenia (COVID suspected) (n=21) and a control group of non-covid patients (n=30). Only one of the patients had a positive swab for SARS-CoV-2, despite this the isolated patients showed increased stress and mood alongside sleep disturbances. The authors call for the appropriate management of patients with severe mental illness when isolated.
Publication date / reference: 19/04/20 Colizzi M et al. Medically unexplained symptoms in the times of COVID-19 pandemic: a case-report. Brain, Behav Immun.
Summary: Single case report of a patient diagnosed with a somatic covid syndrome. Presened with tachycardia, pyrexia, dyspnoea, fatigue, and altered olfactory and gustatory sensitivity. Bloods were normal and he had a negative covid swab.
Publication date / reference: 15/04/20 Zhanga J et al. The differential psychological distress of populations affected by the COVID-19 pandemic. Brain Behav Immun.
Summary: Cross-sectional study finding increased prevalence of depression (29.2%) in patients who experienced COVID-19 infection, while the prevalence of anxiety was not statistically different.
Publication date / reference: 09/04/20 Epstein et al. Anxiety and Suicidality in a Hospitalized Patient with COVID-19 Infection. European Journal Case Reports Internal Medicine.
Summary: Case report of a 34-year-old man who developed symptoms of insomnia and anxiety during his stay on an isolation ward for treatment of SARS-CoV-19. On the 7th day he attempted suicide.
Publication date / reference: 31/03/20 Nguyen HC et al. People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy. J Clin Med.
Summary: Cross-sectional study which indicated that patients with symptoms of COVID-19 had a higher depression likelihood, particularly if they had low health literacy.
Publication date / reference: 27/03/20 Bo HX et al. Posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with COVID-19 in China. Psychol Med.
Summary: Cross-sectional study of 714 recovered and clinically stable COVID-19 inpatients; 96% had significant posttraumatic stress symptoms as defined by scoring ≥50 on the PTSD checklist – civilian version (PCL-C) and 50% considered psycho-educational services helpful.
Publication date / reference: 24/03/20 Yang, L. et al. Analysis of psychological state and clinical psychological intervention model of patients with COVID-19. medRxiv (preprint).
Summary: Prospective observational study of anxiety and depression symptoms. HAM-A and HAM-D scores of COVID-19 patients were higher than healthy controls and pneumonia (non-COVID-19) comparison group.
Publication date / reference: 02/02/20 Zulkifli et al. Brief Psychotic Disorder in Relation to Coronavirus, COVID-19 Outbreaks: A Case Report. Malaysian J Psych.
Publication date / reference: 01/05/2021 Shahjouei et al. SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group. Stroke.
Summary: This large multicenter (136 site) observational study attempted to compare the characteristics of stroke in patients with covid-19 in comparison to pre-pandemic stroke characteristics. The authors observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic
Publication date / reference: 20/04/21. Ahmed et al. Neuro-Imaging Manifestations of COVID-19: Predilection for PICA Infarcts. IDCases.
Summary: The authors report on six cases with posterior inferior cerebellar artery (PICA) infarction, from a consecutive population of 983 COVID-19+ individuals.
Publication date / reference: 21/04/2021 Ziai et al. Transcranial doppler in acute COVID-19 infection: unexpected associations. Stroke.
Summary: The authors of this study conducted transcranial doppler imaging on 16 patients with COVID-19 (two of whom had sustained acute ischaemic stroke secondary to large vessel occlusion) and 10 healthy controls. Comparatively lower cerebral blood flow velocities were observed in COVID-19 patients at median hospital day 4, and these velocities correlated with arterial oxygen content and CRP but not left ventricular ejection fraction.
Publication date/reference: 23/09/2020. Mullaguri et al. COVID-19 Disease and Hypercoagulability Leading to Acute Ischemic Stroke. The Neurohospitalist.
Summary: This brief case-series summarises three patients with ischaemic stroke who tested positive for SARS-CoV-2, of whom only one presented with respiratory failure. The authors therefore highlight the value of SARS-CoV-2 testing in individuals presenting with ischaemic stroke but no respiratory symptoms, particularly in communities with high COVID-19 incidence.
Publication date / reference: 1/3/2021 Shahjouei et al. SARS-CoV-2 Is a Culprit for Some, but Not All Acute Ischemic Strokes: A Report from the Multinational COVID-19 Stroke Study Group. J Clin Med.
Summary: This multicenter prospective study aimed at exploring vascular comorbidity patterns among SARS-CoV-2 infected patients with subsequent stroke and investigated whether the comorbidities and their frequencies under each subclass of TOAST criteria were similar to the AIS population studies prior to the pandemic. The authors included (n=323 AIS) patients from 71 centers in 17 countries. These patients were >6 years younger than other subgroups and more likely were men. The majority of patients suffered from an embolic-appearing stroke on imaging and had about 50% risk of large vessel occlusions. Binominal logistic regression demonstrated that ischemic heart disease, atrial fibrillation, and active neoplasm were associated with cardioembolic stroke.
Publication date / reference: 26/03/2021 Harrison et al. Higher mortality of ischaemic stroke patients hospitalized with COVID-19 compared to historical controls. Cerebrovasc Dis.
Summary: In this large retrospective cohort study Harrison et al identified 954 inpatients across 50 US healthcare organisations with stroke within 30 days of COVID-19 diagnosis using the TriNetX database. Initial comparisons with 48,363 historical controls found that COVID-19 patients with stroke had a higher prevalence of comorbidities and were more likely to be black or African American. After propensity score matching of 952 cases and 952 historical controls Kaplan-Meier survival analysis showed that survival probability was significantly lower in ischaemic stroke patients with COVID-19, with significantly higher odds for 60-day mortality in patients with ischaemic stroke and COVID-19.
Publication date / reference: 30/03/2021 Calmettes et al. Clinical Outcome of Acute Ischemic Strokes in Patients with COVID-19. Cerebrovasc Dis.
Summary: In this retrospective study of admissions for ischaemic stroke in the first lockdown in Paris, the authors compared COVID-19 patients (n = 40) with COVID-19 negative patients (n = 176). On this face of it, COVID-19 stroke patients had worse outcome (mRS scale and mortality) than controls, however when controlling for other factors known to be associated with admission with COVID-19 (e..g obesity), COVID-19 was not a significant risk factor.
Publication date / reference: 4/2021. Bruce et al. Missed cerebrovascular events during prolonged sedation for COVID-19 pneumonia. J Clin Neurosci.
Summary: Bruce and colleagues conducted a retrospective case series, where evidence of ischaemic (n=14) and primary haemorrhagic (n=2) stroke was found on neuroimaging, following a period of prolonged sedation. These findings indicate that sedation, required in severe cases of COVID-19, may limit the detection of clinical signs of stroke.
Publication date / reference: 03/03/2021 Peng et al. Smoking is correlated with the prognosis of coronavirus disease 2019 (COVID-19) patients: an observational study. Front Physiol.
Summary: The authors of this observational study of 622 patients found that there was significantly greater incidence of cerebrovascular disease in smoking patients with COVID-19 as opposed to non-smoking patients with COVID-19 (9.7% vs 3.4%, p = 0.017).
Publication date / reference: 18/03/2021 Khandelwal et al. Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study. Neurosurgery.
Summary: This large retrospective, multi-centre cross-sectional study aimed to look at the incidence and clinical characteristics of Large Vessel Occlusion (LVO) in COVID-19. They assessed 6698 COVID-19 patients that were admitted to stroke centres. Stroke had an incidence of 1.3% and they found LVOs were predominant in patients with ischaemic stroke and COVID-19. These typically occurred in younger patients (median age 51).
Publication date / reference: 24/02/2021 Shen et al., The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation. Front Neurosci.
Summary: This study aims to further epidemiological and mechanistic understanding of the neurological manifestations of COVID-19, using stroke as a case study. Network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome is used to inform the underlying inflammatory mechanisms behind COVID-19 and stroke. Higher vulnerability to severe COVID-19 was found in those with a stroke history, suggesting a monotonic possibly causal relationship between the two.
Publication date / reference: 19/02/2021 Al-Kuraishy et al. COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin. Front Med (Lausanne).
Summary: The authors of this retrospective cohort study aimed to evaluate if risk of acute ischaemic stroke in patients with COVID-19 and type 2 diabetes mellitus (n=42) was associated with differential use of anti-diabetic drugs. This was compared to a group of 21-matched healthy controls. Patients were analysed based on whether they were receiving metformin or non-metformin antidiabetic drugs. The authors found that metformin therapy in diabetics patients was linked to a lower risk of acute ischaemic stroke during COVID-19. Ferritin, CRP and d-dimer levels were also significantly lower in metformin compared to non-metformin treated patients. Conclusive evidence of a protective role for metformin in COVID-19 cannot be determined from this study design.
Publication date / reference: 01/03/21. Leveraging genetic data to elucidate the relationship between Covid-19 and ischemic stroke. medRxiv (not peer-reviewed).
Summary: This is a genetic association study to evaluate putative relationships between critical COVID-19. Based on the author’s analysis, a significant association was detected between critical Covid-19 and ischemic stroke. A Mendellian randomisation analysis determined that liability to critical Covid-19 was associated with increased risk of ischemic stroke (odds ratio per log increase in genetically predicted critical Covid-19 liability of 1.03). However, there was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical Covid-19.
Publication date / reference:7/03/2021. Rass et al. Neurological outcome and quality of life three months after COVID-19: a prospective observational cohort study. Eur J Neurol.
Summary: Prospective, multicentre, observational cohort study (n = 135) which assessed neurological and psychiatric signs and symptoms at 3-month follow-up post COVID-19 infection. Assessment included detailed neurological examination, the 16-item Sniffin-Sticks-test for the assessment of anosmia, Montreal cognitive assessment, 36-item Short Form to assess Quality of Life, the Hospital Anxiety and Depression Scale, and the Post-Traumatic Stress Disorder Checklist-5. At three-month follow-up, 20 patients (15%) presented with one or more neurological symptoms that were not present before COVID-19.
Publication date / reference: 30/01/2021 Vegunta et al. Diagnosis of Stroke on Neuroimaging of COVID-19 Patients in Coma: A Case Series. Cereus.
Summary: Small case series (n = 4) of severely unwell covid-19 patients with impaired consciousness. All patients were mechanically ventilated and, despite not being sedated, were unresponsive. CT scans showed stroke in all four cases.
Publication date / reference: 03/2021. Tabibkhooei et al. COVID-19-associated spontaneous subacute subdural haematoma: report of two cases. New Microbes New Infect.
Summary: Tabibkhooei report two cases of patients with PCR-confirmed COVID-19 infection, who both suffered a spontaneous subdural haematoma. Following both receiving a craniotomy, one patient was discharged the following week and the other patient died three days later.
Summary: This case series reported COVID-19 patients with clinical and radiological characteristics of CVST. The authors found six patients (31-62 years-old) admitted. Four patients had no respiratory symptoms, five patients developed the clinical manifestations of CVST and COVID-19 simultaneously, three patients had known predisposing factors for CVST. Despite receiving CVST and SARS-CoV-2 infection treatments, four patients died. SARS-COV-2 associated CVST patients were older, had lower female/male ratio, and higher mortality rate than CVST not associated with COVID-19. The authors concluded that practitioners should be aware of the possibility of CVST in SARS-CoV-2 infection.
Publication date / reference: 17/02/21. Benny et al. Characteristics and outcomes of 100 consecutive patients with acute stroke and COVID-19. J Neurol Sci.
Summary: In a retrospective study, the authors evaluated 100 consecutive acute stroke patients with COVID-19 from western India. They found that patients with ischemic stroke and COVID-19 were more likely to present with altered sensorium, poor GCS, large vessel occlusion, and multiple territory involvement. However mortality was comparable to patients with ischemic stroke who did not have COVID-19.
Summary: Jain and colleagues report a case series of six patients who suffered strokes whilst receiving ICU treatment for severe COVID-19. One of the patients was extubated and discharged to a neurological rehabilitation facility, whereas two patients remained on mechanical ventilation and with significant neurological damage. Three patients died, two of medical complications and one of brainstem death.
Summary: Lang and colleagues conducted a retrospective observational study which included 163 patients with ARDS, who were split into COVID-19 (PCR confirmed – 47/163), and non-COVID-19 groups. Intracerebral haemorrhage was detected in 22 patients, with no statistically significant difference between the groups.
Publication date / reference: 19/02/2021 Lawton et al. Coronavirus disease 2019 (COVID-19) can predispose young to Intracerebral hemorrhage: a retrospective observational study. BMC Neurol.
Summary: The authors of this retrospective observational study included 22 COVID-19 positive patients and 84 negative patients. Case group mean age was significantly lower and there was significant difference in presence of chronic arterial hypertension, but no difference in gender, diabetes, smoking, GCS, haematoma volume, and hydrocephalus on admission, as well as blood biomarkers.
Publication date / reference: 22/03/2021 Elfasi et al., Impact of COVID-19 on Future Ischemic Stroke Incidence eNeurologicalSci
Summary: This letter outlines current evidence on stroke manifestation in patients with COVID-19, many of which arising from a cardiac source. They also outline long-term cardiac effects in COVID-19 patients and emphasise atrial arrhythmias in these patients being associated with a more severe outcome. They. note the difficulties in determining the exact mechanism of ischemic stroke in this population and the possible future research needed in exacerbating cardiac complications.
Publication date / reference: 9/1/21 Alam et al. Coronavirus positive patients presenting with stroke-like symptoms. J Stroke Cerebrovasc Dis.
Summary: Retrospective case series of patients presenting with stroke symptoms who tested positive for COVID-19 between April and June 2020 (n=17). Most patients had large vessel occlusion infarcts however no embolic source was identified upon further investigations. The authors suggested this may reflect a COVID-19 induced hypercoagulable state. However, most patients displayed conventional risk factors for ischaemic stroke clouding the validity of this conclusion.
Publication date / reference: 04/02/21. Qureshi et al. Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients. Stroke.Summary: The authors conducted a retrospective cohort study to identify risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke, and compared these to patients without COVID-19 and acute ischemic stroke. Using the Cerner de-identified COVID-19 dataset they identified a sample of 8163 confirmed COVID-19 patients, of whom 103 (1.3%) developed acute ischaemic stroke. In 19513 patients without a diagnosis of COVID-19, 199 developed ischaemic stroke (1.0%). Among COVID-19 patients age, ethnicity, and cardiovascular system disease associated with increased stroke risk.
Publication date / reference: 24/12/20. Nahas et al. A case series of ischemic stroke with coronavirus disease 2019 in two Egyptian centers. Egypt J Neurol Psychiatr Neurosurg.
Summary: The authors present 10 cases with cerebrovascular manifestations after developing symptoms of COVID-19 a few days prior to stroke.
Publication date / reference: 08/01/2021 Mishra et al. Intracranial Hemorrhage in COVID-19 Patients. J Stroke Cerebrovasc Dis.
Summary: This was a descriptive retrospective study of patients who presented with stroke and covid-19. In total, eleven patients of a total of 65 who had an intracerebral haemorrhage had confirmed or suspected covid-19. Patients who had ICH tended to have severe covid-19 pneumonia and at least one risk factor for ICH.
Publication date / reference: 18/12/2020. Cezar-Junior et al. Subarachnoid hemorrhage and COVID-19 Association or coincidence?. Medicine (Baltimore).
Summary: Retrospective case series (N=4) of COVID-19 patients who developed spontaneous SAH.
Publication date / reference: 18/01/2021 Ischaemic stroke as an initial presentation in patients with COVID-19: evaluation of a case series in an emergency in Brazil. Neuroradiol J
Summary: This was a retrospective case series (n=30) of COVID-19 patients admitted to a hospital in Fortaleza, Brazil, who presented with acute neurological symptoms and ischaemic stroke. Hypercoagulable and prothrombotic states were observed with laboratory tests in a subgroup of 18 patients, suggesting a cytokine storm syndrome. The authors discuss this as a possible contributing factor in the occurrence of stroke.
Publication date / reference: 11/01/2021. Lee et al. Arterial and venous thromboembolic complications of COVID-19 detected by CT angiogram and venous duplex ultrasound. Emerging Radiol.
Summary: Authors of the study aimed to investigate the incidence of thromboembolic events, specifically pulmonary embolism (PE), deep vein thrombosis (DVT), and cerebrovascular accidents (CVA), in patients who tested positive for COVID-19 through RT-PCR. 3727 (23%) were positive with the virus. Out of those, 192 patients underwent 245 vascular imaging studies including chest CTA, venous duplex ultrasound and CTA head and neck. Among those who underwent imaging 6/25 (24%) had CVA. Results of this study indicate that COVID-19 patients are at increased risk for thromboembolic complications.
Publication date / reference: 18/1/21. Nogueira et al. EXPRESS: Global impact of the COVID-19 pandemic on stroke hospitalizations and mechanical thrombectomy volumes. Int J Stroke.
Summary: This retrospective multicentre observational study aimed to assess the impact of the COVID-19 pandemic on global stroke incidence. 1.45% (n=791/54,366) of COVID-19 hospitalisations had stroke (95% CI; 1.35-1.55), whereas 3.9% (n=784/20,250) (95% CI; 3.61-4.14) of the stroke admissions were diagnosed with COVID-19. However, overall the authors noted a global decline in stroke admissions during the pandemic (-19.2%). It was hypothesised that despite the increase in thromboembolic events associated with COVID-19 the behavioural changes related to the pandemic to avoid seeking medical help.
Publication date / reference: 09/12/20. Daneshi et al. SARS coronavirus 2 and central nervous system manifestations: causation, relation, or coexistence? a case series study and literature review. Br J Neuro.
Summary: This is a case series of five patients with COVID-19 and cerebrovascular events. The patients ranged from 35-85 years old and included a heterogenous pathology including a mix of intraventricular haemorrhage (n= 4), intracerebral haemorrhage (n=3) and infarcts (n=2). The coagulation profile was not deranged in any of the patients. It was not clear based on the authors’ description at what point in the COVID-19 disease course that the cerebrovascular events manifested.
Publication date / reference: 04/12/2020. Ji et al. Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study. Phytomedicine.
Summary: multicenter retrospective study of COVID-19 patients with stroke (N=27). Those with a severe case of the disease, older, with co-morbidities and poor indicators of coagulation had a higher risk of complications. However the study finding is severely limited by the small sample size.
Publication date / reference: 11/12/2020 Kwan et al. Impact of COVID-19 Pandemic on a Regional Stroke Thrombectomy Service in the United Kingdom. Cerebrovasc Dis.
Summary: This is a single-center health service evaluation examining the impact of COVID-19 on a regional stroke-thrombectomy service in the UK. The authors found that the pandemic had a negative impact on stroke admission numbers (falling by 17%), but not on stroke thrombectomy rate, successful recanalisation rate or early neurological outcomes. Interestingly, they also saw an improvement in internal delays for external referrals, attributed to improved efficiency within the department as well a reduced caseload of elective and emergency procedures.
Publication date / reference: 17/10/2020 Beslow et al. Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2. Ann Neurol.
Summary: This multicenter retrospective observational study surveyed 61 international sites with paediatric stroke expertise for the incidence of stroke in a paediatric population from March-May 2020. The authors found that as in adults, stroke was an uncommon complication of SARS-CoV-2 with only 4.7% of those tested testing positive for SARS-CoV-2. In particular the authors highlight that less than 50% of paediatric stroke cases were tested and in future testing should be considered in all paediatric stroke cases.
Publication date / reference: 15/10/2020 Karvigh et al. Ischaemic stroke in patients with COVID-19 disease : A report of 10 cases from Iran. Cerebrovasc Dis.
Summary: In this case series of 10 COVID patients in Iran admitted for ischaemic stroke with concomitant COVID-19, eight patients were reported to develop large infarcts, while two had cardiogenic embolic stroke. However, only 50% of the patients had prior vascular risk factors and stroke occurred within a week of respiratory symptoms with moderate pulmonary involvement. An outstanding characteristic of these stroke patients was the size of the infarct and involvement of large size arteries.
Publication date / reference: 09/12/20 De Havenon et al. Impact of COVID-19 on Outcomes in Ischemic Stroke Patients in the United States. J Stroke Cerebrovasc Dis.
Summary: The authors compared 166,586 ischaemic stroke controls from 2019, versus 2086 ischaemic stroke + COVID-19 cases, from 312 hospitals in 46 American states. Cases were more likely to be male, younger, and Black or Hispanic, with significant increases in morbidity and mortality compared to ischemic stroke controls.
Publication date / reference: Dec 2020. Nwajei et al. Cerebral Venous Sinus Thrombosis in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature. J Stroke Cerebrovasc Dis.
Summary: This retrospective paper presented three cases of patients with SARS-CoV-2 infection who developed cerebral venous sinus thrombosis. The three patients were aged 68, 79 and 25 and all female. All had comorbidities and presentations included nausea, vomiting, weakness, headaches, disorientation, diplopia and papilledema. All three were discharged home after treatment. The authors also searched the literature and found 12 similar cases. The article concluded that the diagnosis, monitoring and treatment of cerebral venous sinus thrombosis in COVID-19 might present unique challenges. The authors called for more large studies in order to guide therapy in this population.
Publication date / reference: 7/12/2020. Dhamoon et al. Acute cerebrovascular events with COVID-19 infection. Stroke.
Summary: This retrospective observational study compared clinical characteristics and outcomes in patients admitted with acute cerebrovascular events. COVID-19 infected stroke patients (38%) were significantly more likely to have lobar stroke and a cryptogenic cause (51.8% versus 22.3%, P<0.0001). COVID-19 infection was also associated with poorer clinical outcomes and in-patient death rate (33% VS 12.9%, P<0.0001) despite similar patient characteristics between COVID-19 positive and negative patients. COVID-19 infection therefore led to poorer outcomes in stroke patients independent of pre-existing physical risk factors.
Publication date / reference: 04/12/2020. Appavu et al. Arteritis and Large Vessel Occlusive Strokes in Children Following COVID-19 Infection. Pediatrics.
Summary: The authors report two interesting COVID-19 paediatric cases of arterial ischemic strokes secondary to post infection arteritis. Both children had elevated markers of systemic inflammation that is inconsistent with a diagnosis of ‘focal cerebral arteriopathy’ however neither would have met the criteria for diagnosis of multisystem inflammatory syndrome in children either due to the absence of fever.
Publication date / reference: 02/11/2020 Al-Mufti et al. Acute Cerebrovascular Disorders and Vasculopathies Associated with Significant Mortality in SARS-CoV-2 Patients Admitted to The Intensive Care Unit in The New York Epicenter. J Stroke Cerebrovasc Dis.
Summary: This prospective case series of hospitalised patients with covid-19 found 48/600 (8%) had associated ischaemic stroke, eight of whom required intensive care support. The authors present a short case series of these eight patients, including three of them who had cerebral artery dissection. Outcomes were poor: three died, one was discharged home, and the other four were discharged to external facilities and continued to require mechanical ventilation.
Publication date / reference: 20/11/2020 Chen et al. High incidence of stroke in COVID-19 patients. Aging.
Summary: In this (n = 2037) retrospective review the authors found 11 strokes (0.5%) in admitted COVID-19 patients. Although the authors found this to be higher in comparison to usual admissions, this prevalence is lower than in much of the covid-19 literature. As author research has indicated, D-dimer was raised in COVID-19 patients with stroke and they felt that it can be used as an early warning indicator of cerebral infarction.
Publication date / reference: 19/11/2020 Richter et al. Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. A Nationwide analysis. Neurol Res Pract.
Summary: This study compared the treatments of patients with acute ischaemic stroke in COVID-19 and non-COVID-19 populations. The rate of thrombolysis was identical, however the rates of mechanical thrombectomy was less than half in the former (3.8% vs. 7.9%). In addition, stroke patients were much more likely to die if they had COVID-19 (22.5% vs. 7.8%). The authors did not set out to analyse prevalence of acute ischaemic stroke in covid-19, but nevertheless it was on the lower endof estimates from the COVID-19 literature (0.7%).
Publication date / reference: 01/11/20. Fayed et al. Intracranial hemorrhage in critically ill patients hospitalized for COVID-19. J Clin Neurosci.
Summary: The authors reported 3 cases of spontaneous intracranial haemorrhage in critically ill COVID-19 patients receiving ventilatory support. The cases are in line with growing evidence that COVID-19 patients are at increased risk of developing intracranial haemorrhage. The authors postulated that tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via ACE-II receptors may be a possible underlying pathogenesis pathway.
Publication date / reference: 23/11/2020 Mac Grory and Yaghi. Response by Mac Grory and Yaghi to Letter Regarding Article, “SARS-CoV-2 and Stroke in a New York Healthcare System”. Stroke.
Summary: MacGrory and Yaghi respond to correspondence from Bayona et al, who question whether the high incidence of cryptogenic stroke in their original article was an overestimation due to misclassification. Bayona et al point out that the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system includes hypercoagulability under “other determined aetiology”. The authors acknowledge the challenges of attributing causality. They maintain that there are many contributing mechanisms to stroke in COVID-19, beyond acute hypercoagulability, and explain their reasoning for their classification.
Publication date / reference: 23/11/20. Cagnazzo et al. European Multicenter Study of ET-COVID-19. Stroke.
Summary: The authors of the ET-COVID-19 study (Endovascular Thrombectomy in COVID-19 Patients) aimed to study early outcomes after mechanical thrombectomy in patients with COVID-19. They conducted a multicentre cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium, with data for the current paper collected between March and May 2020. They included consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with mechanical thrombectomy. The primary outcome was 30-day mortality. Of n=93 patients, acute ischaemic stroke in the anterior circulation represented the majority (83 patients). The most common sites of occlusion were M1 (n=46) and M2 (n=16), followed by the carotid terminus (n=13). Tandem occlusion occurred in nine patients with basilar artery occlusion in six further cases. Mortality at 30 days was 27/93 [29%, 95%CI, 20–39.4]). The primary cause of mortality was neurological (associated with ICH or malignant cerebral infarction/edema) in 14 patients and non-neurological (respiratory failure and multiorgan failure) in 13 patients.
Publication date / reference: 23/11/2020 Uchino and Cho. Letter by Uchino and Cho Regarding Article “Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19: A Snapshot in Time”. Stroke.
Publication date / reference: 23/11/2020 Sparr and Bieri. Response by Sparr and Bieri to Letter Regarding Article, “Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19: A Snapshot in Time”. Stroke.
Summary: Uchino and Cho point out other radiological studies in critically ill, mechanically ventilated COVID-19 patients which have shown frequent occurrences of (otherwise rare) cerebral infarcts and microhaemorrhages in the splenium of the corpus callosum, such as those reported by Sparr and Bieri. They suggest the possibility that this may be due to a microangiopathic process common among patients with critical illness, regardless of COVID-19 status. Sparr and Bieri have cited, in response, several larger imaging studies showing a wide range of imaging findings on MRI, including hyperintense lesions in the splenium of the corpus callosum. They maintain that the splenium of the corpus callosum seems unusually susceptible to injury in patients with severe COVID-19 but concur that none of these findings and patterns of injury are unique to the disease itself.
Publication date / reference: 21/11/20. Katsanos et al. The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-analysis. Ann Neurol.
Summary: This is a meta-analysis examining the potential impact of COVID-19 on the management and outcomes of acute stroke. 18 cohort studies, including 67845 patients were identified. The authors report that among patients with SARS-CoV-2, 1.3% were hospitalized for cerebrovascular events, 1.1% for ischemic stroke, and 0.2% for hemorrhagic stroke. Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR=3.58) and cryptogenic stroke (no clear attributable cause) (OR=3.98). Diabetes mellitus, known to be a significant risk factor for stroke, was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls (OR=1.39). Odds for in-hospital mortality were higher among SARS-CoV-2 stroke patients – approximately five-fold (OR=5.60), compared to non-infected contemporary or historical stroke patients. The authors suggest that the increased risk of ischemic and cryptogenic stroke could be related to blood hyper-viscosity and a hypercoagulable state that has been linked to an immune-mediated response following SARS-CoV-2 infection.
Publication date / reference: 06/11/20 Sabayan et al. COVID-19 respiratory illness and subsequent cerebrovascular events, the initial Iranian experience. J Stroke Cerebrovasc Dis.
Summary: The authors of this study utilised the Iranian Neurological Association to gather fifteen cases across the country of neurological symptoms secondary to stroke after definite or probably COVID-19.11/15 patients had previous cardiovascular comorbidities and median time from respiratory symptoms to neurological symptom onset was seven days. Stroke severity was severe in 7/15 and moderate in 6/15 (NIHSS), mortality was 6/15 and all but one surviving patient demonstrated significant disability on a modified ranking scale.
Publication date / reference: 11/11/2020 Wang et al., COVID-19 Associated Ischemic Stroke and Hemorrhagic Stroke: Incidence, Potential Pathological Mechanism, and Management. Front Neurol.
Summary: This article aims to explain various mechanisms pertaining to the CNS involvement in COVID-19 infected patients. Mechanisms for invasion of the CNS include hematogenous and neuronal routes – via ACE2 receptors or retrograde axonal transport. It also explains the evidence for COVID-19 infection causing a procoagulant state and thus inducing venous and arterial thromboembolism. They also talk about the possible mechanism and management of patients with COVID-19 related stroke. The authors conclude that further studies need to be done to ascertain the exact links between cerebrovascular disease and COVID-19.
Publication date / reference: 06/11/2020 Dakay et al. Cerebral Venous Sinus Thrombosis in COVID-19 Infection: A Case Series and Review of The Literature. J Stroke Cerebrovasc Dis.
Publication date / reference: 02/11/20 Akhtar et al. Characteristics and Comparison of 32 COVID-19 and Non-COVID-19 Ischemic Strokes and Historical Stroke Patients. J Stroke Cerebrovasc Dis.
Summary: This retrospective cohort study compared admission rates for stroke and their phenotype in the 6 months prior to SARS-CoV-2 and during the COVID-19 pandemic. They found that stroke numbers declined marginally during the COVID-19 pandemic. They found that patients who suffered strokes who were SARS-CoV-2 positive were typically younger, had less incidence of hyperlipidaemia, diabetes and hypertension and had more cortical and severe strokes with longer hospitalisation.
Publication date / reference: 02/11/20 Mousa-Ibrahim et al. Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series. J Stroke Cerebrovasc Dis.
Summary: In their report Mousa-Ibrahim et al. present 6 cases of patients with COVID- 19, who received anticoagulant treatment and developed intracranial hemorrhage (ICH). Five of these patients were critically ill with COVID ARDS and developed ICH while on intermediate or full-dose therapeutic anticoagulation. One patient was SARS-CoV-2 positive but asymptomatic and suffered intracranial hemorrhage after prophylactic anticoagulation. The authors conclude that as therapeutic coagulation comes with increased risk of bleeding, clinicians must carefully balance the risks and benefits of anticoagulation in COVID-19 patients.
Publication date / reference: 28/09/20. Haroon et al. COVID-19 Related Cerebrovascular Thromboembolic Complications in Three Young Patients. Case Rep Neurol.
Summary: The authors reported the cases of three young patients who suffered cerebrovascular thrombolic complications secondary to SARS-CoV-2 infection. The first patient had mild to moderate COVID-19 severity, whilst the second and third had mild infection. The first and third patients presented with stroke at the onset of COVID-19 whilst the second developed a stroke two weeks after the onset of symptoms, suggesting that SARS-CoV-2 infection-associated thromboembolism can occur both early and later in the disease course.
Publication Date/Reference: 09/12/2020. Elkhider et al. COVID-19 and stroke, a case series and review of literature. Brain Behav Immun Health.
Summary: Case-series of 4 COVID-19 patients who were all under 60 years old and suffered ischemic strokes as a complication. The authors discussed several possible mechanisms linking leading to the increased risk of ischemic stroke in COVID-19 patients, including hypercoagulability, vasculitis, new onset atrial fibrillation and direct result of the viral infection.
Publication date / reference: 09/11/2020. Smilowitz et al., Thrombosis in Hospitalized Patients with Viral Respiratory Infections versus COVID-19. Am Heart J.
This is a case-control study aimed at evaluating the incidence of thrombosis in patients hospitalised with non-COVID-19 acute viral respiratory illnesses (adult patients from 2002-2014) compared to patients with COVID-19. Within the non-COVID-19 viral pneumonia group, acute MI occurred in 2.8% of hospitalisations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%.The authors found that the proportion of hospitalisations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs. 16%; p<0.001). This is the largest series to evaluate risks of in-hospital thrombosis among patients with non-COVID-19 respiratory illnesses, a majority of which were due to viral influenza.
Publication date / reference: 03/11/2020. Cheruiyot et al.Intracranial hemorrhage in coronavirus disease 2019 (COVID-19) patients. Neurol Sci.
Summary: This systematic review looked at the link between COVID-19 patients developing or presenting with cerebrovascular disease. 23 studies were analysed comprising of n=148 COVID-19 patients with ICH. The authors note that the incidence of ICH in these patients was 0.7% (95% CI 0.5–0.9). Most of these COVID-19 patients with ICH were male (65.8%), the majority of patients were over 50 years of age. The most common type of ICH in these patients were intraparenchymal haemorrhage (62.6) %, closely followed by SAH (15.0%). The majority of patients developed ICH during their admission rather than presenting with it (71%). Pre-existing co-morbidities were present in these patients including: hypertension, DM and hyperlipidaemia. Concerning outcomes, mortality was 48.6%.
Publication Date/Reference: 5/11/20 Perry et al. Characteristics and outcomes of COVID-19-associated stroke: a UK multicentre case-control study. J Neurol Neurosurg Psychiatry.
Summary: This case-control study aims to determine characteristics and outcomes of stroke associated with COVID-19. The authors included patients admitted with stroke and COVID-19 (n=86) compared with stroke patients without COVID-19 who admitted during the same time period (n=1,384). They found that cases with ischaemic stroke were more likely than ischaemic controls to occur in Asians, more likely to involve multiple large vessel occlusions, more severe, higher D-dimer levels, and more severe disability on discharge and inpatient death. Recurrence of stroke during the patient’s admission was rare in Cases and Controls. They concluded that COVID-19 may be an important modifier of the onset, characteristics and outcome of acute ischaemic stroke.
Publication Date/Reference: 27/10/2020 Bekelis et al. Ischemic Stroke Occurs Less Frequently in Patients With COVID-19: A Multicenter Cross-Sectional Study. Stroke.
Summary: This large scale cross-sectional study reviewed the incidence of stroke and COVID-19 among discharged from January to April 2020 in the state of New York. A total of 10.1% had COVID-19 while 0.2% presented with acute ischaemic stroke. Surprisingly the authors found that having COVID-19 was associated with a one-quarter odds of having ischaemic stroke across all age groups and stayed significant in sensitivity analyses and propensity-weighted regression models. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. The authors explore some proposed hypotheses for this decreased incidence but increased mortality of ischaemic stroke in COVID-19 from the wider literature and finally call for longer term follow-up of these patients to evaluate if any increased longer term complications occur.
Publication Date/Reference: 29/10/20. Katz et al. COVID-19 severity and stroke: correlation of imaging and laboratory markers. AJNR Am J Neuroradiol.
Summary: The authors of this study conducted a retrospective case series of COVID-19 patients with imaging-confirmed stroke (n=86) between March 14 and April 26, 2020. Comparisons revealed that patients with stroke already hospitalised for severe COVID-19 (n=41) had significantly more frequent infarctions, with multivascular distributions and associated haemorrhage, than patients with out-of-hospital stroke onset and milder or no COVID-19 symptoms (n=45). In addition, patients with stroke admitted with more severe COVID-19 had significantly higher CRP, ferritin and D-dimer levels, as well as more frequent lymphopenia, and renal and hepatic injury.
Publication Date/Reference: Oct, 2020. Alharthy et al., Life-threatening COVID-19 presenting as stroke with antiphospholipid antibodies and low ADAMTS-13 activity, and the role of therapeutic plasma exchange: A case seriesSAGE Open Med Case Rep.
Summary: This case series (n=3) included ICU COVID-19 patients with imaging showing confirmed brain infarctions. All cases were given plasma exchange. The findings suggest that high severity COVID patients who are showing immune dysregulation signs, plasma exchange can be effective.
Publication Date/Reference: 30/10/2020. Lan et al. Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the USA. Occup Environ Med.
Summary: Cross sectional study of workers from a single grocery store (N=104). 20% of workers tested positive for SARS-Cov-2, 76% of which were asymptomatic. The study also reported a 24% prevalence of depression (PHQ-9 score>4) and 8% prevalence of anxiety (GAD-7 score >4). Those able to practice social distancing had consistently lower risk for anxiety and depression (OR =0.1).
Publication date / reference: Nov, 2020 Requena et al., COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center. J Stroke Cerebrovasc Dis
This single-centre retrospective study aimed to evaluate the association between acute stroke in COVID-19 patients. They studied SARS-CoV-2 positive patients (n=2050) with stroke diagnoses. Of these, 21 (1.02%) presented with acute ischaemic stroke and 4 (0.2%) had intracranial haemorrhage. Only n=6 patients with diagnosed stroke were thought to be related to COVID-19; all of these patients required mechanical ventilation prior to stroke onset. The key findings suggested that the presence of acute stroke was only found in 0.2% of patients, who all had previous stroke risk factors and for most, a cause was identified. Of these, the most prominent was hypertension n=14/25 (56.0%). Regarding outcomes, of the n=25 stroke patients, 8 (32.0%) warranted ICU admission,14 (56.0%) had severe infection, and 10 (40.0%) had in hospital mortality.
Publication date / reference: Nov, 2020 Carneiro et al., Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19 J Stroke Cerebrovasc Dis
This is a multicentre case series (9 centres) evaluating patients with COVID-19 and acute neurological deficits who were treated with IV tPA (n=13). Three patients (n=3) underwent mechanical thrombectomy. The authors found that CT angiography revealed large vessel occlusion (LVO) in 8 cases (61.5%) and MRI brain confirmed acute ischemic stroke in 4 cases (30.7%). They also found that the most common stroke mechanism was cardioembolic (n=3). Administering IV tPA in their sample did not show any further complications and at follow-up showed clinical improvement. 8 (61.5%) patients had an improvement in their NIHSS score of 4 points or more and all except one patient was discharged home. The authors conclude that IV tPA was safe to use in acute ischemic stroke patients with COVID-19. However larger studies should be done to investigate this further.
Publication date / reference: 09/20. Kananeh et al. Arterial and venous strokes in the setting of COVID-19. J Clin Neurosci.
Summary: This retrospective study examined patients presenting to a large tertiary care centre in the US with stroke and COVID-19. Four patients were presented including characteristics on medical history, disease severity and laboratory findings. There were three cases of arterial ischaemic strokes and one case of venous stroke: Three males and one female. The mean age was 55 (48-70) years. All arterial strokes presented with large vessel occlusions and had mechanical thrombectomy performed. Two of the cases presented despite adequate anticoagulation being prescribed. The authors called for further studies needed in order to understand the role of anticoagulation in stroke patients.
Publication date / reference: 10/09/20. Ghanchi et al. Racial disparity amongst stroke patients during the coronavirus disease 2019 pandemic. Cureus.
Summary: The authors of this US study reviewed the ‘Get with the Guidelines National Stroke Database’ to assess patients presenting with stroke between February – May 2020. A downward trend in the total number of patients presenting with stroke during this period of the pandemic was noted. A statistically significant increase in Black and Hispanic patients presenting with stroke was noted in California, Pacific hospital, Western hospitals and all US hospitals was observed during various months when comparing 2020 to 2019.
Publication date / reference: 14/10/20. Mowla et al. Cerebral venous sinus thrombosis associated with SARS-CoV-2; a multinational case series. J Neurol Sci.
Summary: Case series of COVID-19 patients presented with Cerebral venous Sinus thrombosis (CVST) (N=13). Compared with non-Covid control groups, the SARS-CoV-2 infected patients were significantly older, had a lower rate of identified CVST risk factors, more frequent cortical vein involvement, and a non-significant higher rate of in-hospital mortality.
Publication date/ reference: 15/10/2020. Emanuella Keller et al. Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series. Stroke.
Summary: This case series assess large and small cerebral vessel involvement in severe COVID-19. The authors concluded that central nervous system disorders associated with COVID-19 could lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.
Publication date / reference: 29/11/20. Anand et al. Posterior Reversible Encephalopathy Syndrome in Patients with Coronavirus Disease 2019: Two Cases and A Review of The Literature. J Stroke Cerebrovasc Dis.
Summary: Case report of two COVID-19 patients with posterior reversible encephalopathy syndrome (PRES)
Publication date / reference: 09/20. Pirau et al. Case Series: Evidence of Borderzone Ischemia in Critically-Ill COVID-19 Patients Who “Do Not Wake Up”. Front Neurol.
Publication date / reference: 14/10/2020 Yao et al. The clinical characteristics and prognosis of COVID-19 patients with cerebral stroke：a retrospective study of 113 cases from one single center. Eur J Neurosci.
Summary: In this retrospective notes review, researchers found that 1.0% of patients admitted to hospital had new-onset stroke associated with covid-19. Unsurprisingly, stroke was associated with poorer mortality rates, which was posited to be mediated by multiorgan dysfunction and an ‘overactivated’ inflammatory response.
Publication date / reference: 12/09/20. Nallebelle et al. Coronavirus Disease 2019 in Patients with Prior Ischemic Stroke. Cureus.
Summary: Nalleballe and colleagues utilised the TriNetX global COVID-19 database and aimed to investigate if patients with prior history of ischemic stroke are vulnerable to COVID-19.
Of those identified with a history of ischemic stroke (n=604,258), 0.15% developed COVID (n= 891). The investigators found that compared to control (n= 32,136), those with previous history of ischemic stroke tend to be older with multiple comorbidities which contributed to more severe COVID-19 complications.
Publication date / reference: 17/09/20. Tiwari et al. Etiologic Subtypes of Ischemic Stroke in SARS-CoV-2 Patients in a Cohort of New York City Hospitals. Front Neurol.
Summary: In this multi-site prospective cohort study, Tiwari and colleagues explored the characteristics of ischaemic stroke in patients hospitalised with COVID-19 during a peak period in the pandemic (PCR-confirmed). The vast majority (81%) had known vascular risk factors and ischaemic stroke was an acute complication in the COVID-19 disease course, occurring a median of 4 days from symptoms onset. There was an equal split between large vessel (LVO) and non-large vessel occlusion (NLVO) strokes (n=8 in each). Sub-group analysis revealed that LVO patients tended to be younger, had significantly higher mortality and raised acute phase reactants (except d-dimer) when compared to the NLVO group. The most common stroke aetiology was cryptogenic.
Publication date / reference: 09/10/2020. Mathew et al. COVID-19 Related Strokes are associated with increased mortality and morbidity: A multi-center comparative study from Bengaluru, south India. Int J Stroke.
Summary: Multicentre retrospective study (13 hospitals) of COVID-19 associated stroke. Most of the 62 included patients (97%) had ischaemic stroke. Based on a comparison with non-covid strokes, those associated with SARS-CoV-2 infection were of a more severe nature.
Publication date / reference: 15/9/2020. Bihlmaier et al. Disseminated Multifocal Intracerebral Bleeding Events in Three Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation As Rescue Therapy. Crit Care Explor.
Summary: Describes an unusual white matter multifocal bleeding pattern in three patients suffering from acute respiratory distress syndrome secondary to COVID-19 who required extracorporeal membrane oxygenation. They used clinical examination, CT and post-mortem examination. Neuropathological analyses found cerebrovascular occlusions which lead to microvascular and then macrovascular bleeding events. They use this as a basis for further consideration of bleeding risk and systemic anticoagulation strategies for patients suffering from COVID-19.
Publication date / reference: 24/08/2020. Shekhar et al. Neurological Complications Among Native Americans with COVID-19: Our Experience at a Tertiary Care Academic Hospital in the U.S. J Stroke Cerebrovasc Dis.
Summary:. Retrospective single center study for CNS complications in patients hospitalized with Covid -19 (N=90). Of the total screened seven were found with CNS complications (subarachnoid hemorrhage (SAH), Intraparenchymal hemorrhage (IPH), Ischemic stroke (IS) and seizure), all were Native Americans. Authors reported clinical characteristics of each patient, there was no long term follow up.
Publication date / reference: 06/10/20. Kihira et al. Neurovascular complications that can be seen in COVID-19 patients. Clin Imaging.
Summary: Case series of neurovascular complications in 4 covid-19 positive patients.
Publication date / reference: 31/08/20. Rajdev et al. Acute Ischemic and Hemorrhagic Stroke in COVID-19: Mounting Evidence. Cureus.
Summary: Rajdev and colleagues present a series of three patients presenting with COVID-19 and stroke. In two cases, the patient presented to hospital with sudden onset right sided weakness and were later diagnosed with ischaemic stroke. The third patient sustained an acute intracerebral haemorrhage as an inpatient. In all three cases, SARS-Cov-2 was elicited as being a precipitant for the stroke. The authors conclude that there should be a low threshold for suspecting stroke in patients with COVID-19 and that patients with cardiovascular risk factors should be closely monitored.
Publication date / reference: 20/08/20. Grewal et al. Acute Ischemic Stroke and COVID-19: Experience From a Comprehensive Stroke Center in Midwest US. Front Neurol.
Summary: This retrospective study looked at patients hospitalised with acute ischaemic stroke (AIS) and SARS-CoV-2 infection within a comprehensive stroke center in Chicago, IL. The authors reviewed stroke characteristics, etiologies and composite outcomes. The cohort was compared with historic patients with AIS without COVID-19 admitted in the year previous. Of the 13 patients with AIS and COVID-19, Latinos and African-Americans comprised the majority of the cohort (76.8%). Most strokes were cortical (84.6%) and more than 50% of patients had no identifiable source and were therefore characterised as embolic stroke of unknown cause. Less alteplase administration was noted in the COVID-19 AIS group as compared to the non-COVID-19 2020 group (7.1% vs. 20.7% p=0.435). Systemic thrombotic complications occurred in three of the COVID-19 patients. Eight patients were discharged home or to acute rehabilitation and two deceased from COVID-19 complications. The authors concluded that AIS in the setting of COVID-19 is associated with worse outcomes, especially among African-American and Latino populations.
Publication date / reference: 24/09/20. Bach et al. Stroke in COVID-19: a single-centre initial experience in a hotspot of the pandemic. Stroke Vasc Neurol.
Summary: This study retrospectively examined all patients admitted to their hospital in New Jersey, USA, with positive RT-PCR swab tests for SARS-CoV-2. Acute ischaemic strokes (AIS) were identified and the demographics, clinical, laboratory, imaging characteristics, treatments and outcomes were reviewed. 683 positive patients were identified, 20 of which had AIS. Large vessel occlusion was identified in 11 patients. Intravenous alteplase was administered in four patients and mechanical thrombectomy was performed in five patients. Respiratory symptoms preceded the onset of AIS in most of the patients (70%) by 1 to 21 days. Mortality in patients with AIS was 50% compared to 26% of all COVID-19 admissions. However, most of these patients died due to non-neurological causes. The authors concluded that large vessel occlusion was more common in patients with AIS and COVID-19 despite the lack of a control group.
Publication date / reference: 24/09/20. Melmed et al. Risk factors for intracerebral hemorrhage in patients with COVID-19. J Thromb Thrombolysis.
Summary: This study aimed to assess risk factors associated with intracerebral haemorrhage (ICH) in a population of adult patients admitted to NYU Langone Health system with a positive SARS-CoV-2 swab test. Among 3824 patients admitted with COVID-19, 755 had neuroimaging and 416 were identified after the exclusion criteria were applied. The mean age was 69.3 and 35.8% were women. ICH occurred in 33 patients. Older age, non-caucasian race, respiratory failure requiring mechanical ventilation and therapeutic anticoagulation were associated with ICH on univariate analysis (p<0.01 on each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p<0.001). ICH was also associated with increased mortality (OR 2.6, 95% CI 1.2-5.9). The authors concluded that anticoagulation use was associated with increased risk of ICH in COVID-19 patients. They called for further investigation into the potential underlying mechanisms and prevention strategies in these populations.
Publication date / reference: 18/09/20. Pata et al. Probability of COVID-19 Being the Culprit in Neurocognitive Deception: A Case Series of Incidental Strokes in ICU Patients With COVID-19. Cureus.
Publication date / reference: 18/09/20. Jillella et al. Ischemic stroke in COVID-19: An urgent need for early identification and management. PLoS One.
Publication date / reference: 17/09/20. Siddiqui et al. COVID-19 Stroke Apical Lung Examination Study: A Diagnostic and Prognostic Imaging Biomarker in Suspected Acute Stroke. AJNR Am J Neuroradiol.
Publication date / reference: 12/09/20. Siepmann et al. Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis. Eur J Neurol.
Summary: The authors conducted a multi-centre retrospective case-note review of the prevalence of stroke in 165 confirmed COVID-19 patients. They also conducted a systematic review of stroke prevalence to calculate a pooled prevalence estimate. In the cohort study a requirement for intensive care independently predicted stroke, with an estimated prevalence of 4.2%. The meta-analysis returned a pooled prevalence estimate of 2.9%. This pooled figure masked a possible differential split between mild (1.7%) and severe (5.5%) forms of COVID-19. The search extended until May 19th, and the meta-analysis included only two studies.
Publication date / reference: 13/09/20. Mowla et al. Cerebral Venous Sinus Thrombosis Associated with SARS-CoV-2; a Multinational Case Series. MedRxiv (preprint).
Summary: The authors collected 13 cases of CVST (eight female) in SARS-CoV-2 infected patients admitted to nine tertiary stroke centers from the beginning of the pandemic to June 30th, 2020. They compared the demographics, clinical and radiological characteristics, risk factors, and outcome of these patients with a control group of non-SARS-CoV-2 infected CVST patients in the same seasonal period of the years 2012-2016. Compared to controls, SARS-CoV-2 infected patients with CVST were significantly older, with a lower rate of identified CVST risk factors, more frequent cortical vein involvement and a higher rate of in-hospital mortality.
Publication date / reference: 08/09/20. Jensen et al. Neuropathological findings in two patients with fatal COVID-19. Neuropathol Appl Neurobiol.
Summary: The authors report two cases of fatal COVID-19 as well as the pathology observed through autopsy and histological analysis. The first case displayed severe multifocal cortical infarctions consistent with severe multi-territorial cerebral vascular injury, whilst the second case displayed a brainstem encephalitis centered on the dorsal medulla as well as subacute regional infarct involving the cerebellar cortex. In both cases it was noted that in situ hybridisation and RT-PCR for SARS-CoV-2 RNA were negative in tissue sampled from the area of pathology, which the authors suggest may indicate that these are para-infectious phenomena from systemic hyperinflammation and hypercoagulable state.
Publication date / reference: 01/09/20. Lin et al. Racial differences and an increased systemic inflammatory response are seen in patients with COVID-19 and ischemic stroke. Brain Behav Immun Health.
Summary: This retrospective observational study reviewed patients admitted for acute ischaemic stroke to a single centre in the United States between March to May 2020. 60 patients were admitted for ischaemic stroke during this period of which 9 tested positive for COVID-19. These nine patients had an average age of 58.21; three were male and five were African American. Patients with infection had a more severe neurological deficit on presentation (higher NIHSS), increased inflammatory response (increased neutrophil to lymphocyte ratio- NLR) and increased mortality (44.4% vs. 7.6%) compared with those patients with no infection. These results should be taken with extreme caution due to the small COVID-19 sample size and as the absolute number of african-americans in the infected group was only one greater than the non-infected group, the effects of racial disparities in stroke are difficult to assess. Despite this the authors build on previous studies comparing stroke in groups with and without COVID-19 infection that haven’t addressed racial differences or systemic inflammation. As African Americans genetic variations are associated with inflammation it provides an additional avenue of research for future studies to explore the racial disparities in stroke outcomes. The authors propose that as the NLR is a well studied biomarker of inflammation in COVID-19 and the constituent blood tests are carried out routinely it may be a cost-effective marker in helping assess disease severity and predict complications.
Publication date / reference: 07/09/20. Kwon et al. Characteristics of Acute Stroke in Patients with Coronavirus Disease 2019 and Challenges in Stroke Management during an Epidemic. J Korean Med Sci.
Summary: In a retrospective case note review, the authors describe another five patients with COVID-19 and ischemic stroke.
Publication date / reference: 28/07/20. Usman et al. A Case Series of Devastating Intracranial Hemorrhage During Venovenous Extracorporeal Membrane Oxygenation for COVID-19. J Cardiothorac Vasc Anesth.
Summary: This retrospective case-series (n=10) described devastating intracranial haemorrhage in COVID-19 patients supported with extracorporeal membrane oxygenation (ECMO). An inclusion criteria was set consisting of severe refractory ARDS due to COVID-19, failure of proning therapy with muscle relaxant infusion and ECMO initiation. The primary outcome was the incidence of any type of stroke for the duration of ECMO. Diagnosis of stroke was suspected via bedside findings of local neurological deficits, notably an abnormal pupillary examination in patients treated with heavy sedation and neuromuscular blockade. Four patients had haemorrhagic strokes during ECMO treatment, three were intraparenchymal and one was mild SAH. The authors noted previous studies with lower rates of ICH in ECMO support, and raised that venovenous ECMO has much different anticoagulation requirements. Study limitations included the low number of participants and the limited value of aPT testing for prediction of actual coagulation status in COVID-19. The authors concluded that COVID-19 is not a prothrombotic condition alone and actually causes severe imbalances in bleeding and thrombotic risk.
Publication date / reference: 24/08/20 Kvernland et al. Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System. Neurocrit Care.
Summary: This retrospective cohort study (n=4071) examined patients with haemorrhagic stroke who were hospitalised between March 1st 2020 and May 15th 2020 in New York during the COVID-19 pandemic. Both patients who developed haemorrhagic stroke on admission and those who developed haemorrhagic stroke during hospitalisation were included. Clinical characteristics and demographic variables were compared between those with COVID-19 and without COVID-19. Of the total sample, 34 patients with COVID-19 had haemorrhagic stroke. 15 were then excluded due to a diagnosis of haemorrhagic transformation of ischaemic stroke. 84.2% of those with COVID-19 who developed stroke required mechanical ventilation and the mortality rate at discharge was 84.6%. Coagulopathy was the most common etiology of haemorrhagic stroke with a prevalence of 73.7%. Of the 17 patients on anticoagulation (two not prescribed), the goal intensity was full therapeutic range. 10/17 were supratherapeutically anticoagulated before stroke development. The authors concluded that they had seen a relatively low rate of haemorrhagic stroke in hospitalised patients with COVID-19 and urged large studies to further validate the clinical characteristics found in the study.
Publication date / reference: 27/08/20 Lang et al. Risk of acute cerebrovascular events in patients with COVID-19 infection. AJNR Am J Neuroradiol.
Summary: The authors of this letter describe how between March 2th 2020 and April 10th 2020, 468 patients at a single institution were tested positive for COVID-19, 105 of whom underwent neuroimaging. Six cases were seen to have sustained an acute cerebrovascular event, four of which were haemorrhagic and two of which were ischaemic. No significant difference in age or comorbidities was seen between COVID-19 patients with or without acute cerebrovascular events.
Publication date / reference: 27/08/20 John et al. Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke. AJNR Am J Neuroradiol.
Summary: This retrospective cohort study assessed patients with COVID-19 presenting with ischemic stroke from March 1st 2020 to May 25th 2020. Of 20 patients with COVID-19 and acute ischaemic stroke 15 had large vessel occlusion, average patient age was 46.5 years and patients were predominantly male (93%) and free from major burden of classic cardiovascular risk factors. Large vessel occlusions were detected in multiple vessels in 40% of cases and systemic thrombosis separate from large-vessel occlusion was seen in 26% of cases.
Publication date / reference: 13/08/20 Dmytriw et al. Ischaemic stroke associated with COVID-19 and racial outcome disparity in North America. J Neurol Neurosurg Psychiatry.
Summary: This retrospective multi-centre study builds on the finding that the mortality rate of COVID-19 patients with stroke is greater than that reported in COVID-19 alone. The authors compared and contrasted the co-morbidities, treatment received, laboratory tests and stroke outcomes of confirmed COVID-19 patients by race. 27 African american patients were compared with 42 non-african americans, made up of caucasian, hispanic and asian participants. The authors used either t-tests or Wilcoxon rank sum test to compare participants on a range of variables. They found that African-American participants were significantly more likely to have diabetes mellitus, higher LDL, symptomatic intracranial haemorrhage, and higher mortality. The authors discuss a range of possible causes for the racial disparities but caution readers in interpretation pending larger-scale studies.
Publication date / reference: 19/08/20. Escalade et al. Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients. Stroke.
Summary: In this comparative cohort study, Escalard and colleagues compared patients with PCR-confirmed COVID-19 who had anterior circulation large vessel occlusion (aLVO) and early brain imaging within 3 hours from onset (n=12) with a control group admitted during the same period in 2019 (n=34). The authors found that patients in the COVID-19 group had more severe strokes with a significantly lower clot burden score, higher rate of multivessel occlusion, higher infarct core volume and higher in-hospital mortality. The authors found no difference between the groups in terms of successful recanalization rate, time of onset to imaging and the National Institutes of Health Stroke Scale. The baseline characteristics of the groups were similar, however, the COVID-19 group was younger with a higher frequency of diabetes mellitus. Although the sample was small and selected, the authors concluded that patients with COVID-19 had more severe strokes than patients without COVID-19.
Publication date / reference: 13/08/20. Pop et al. Stroke Thrombectomy in Patients with COVID-19: Initial Experience in 13 Cases. AJNR Am J Neuroradiol.
Summary: In this retrospective review Pop and colleagues examined patient cases over a two month period in two stroke units. They identified those who underwent mechanical thrombectomy for acute ischemic stroke who also had a confirmed SARS-Cov2 infection (n=13), representing one third of all patients who underwent stroke thrombectomies during this period. They note that in most cases patients did not have a COVID-19 diagnosis/suspicion before the acute stroke presentation. Limited by the small sample size, the authors were restricted to reporting descriptive findings only. They report an increased mortality rate (15.3%) and higher rate of thrombotic complications during hospitalization (DVT=23%, PE=7.6%) in this cohort of patients. Based on these findings, the authors call for full PPE measures for all stroke thrombectomies performed during the pandemic period.
Publication date / reference: 17/08/20. Shahjouei et al. Risk of stroke in hospitalized SARS-CoV-2 infected patients: a multinational study. EBioMedicine.
Summary: The authors of this large multicentre, multinational observational study received data on 26,175 hospitalised patients infected with SARS-CoV-2 from 99 tertiary centres across 65 regions of 11 countries until May 1st 2020. 17,799 patients had sufficient clinical data to be included in meta-analyses, of whom 156 (0.9%) had sustained a stroke. Of patients who had a stroke, 123 (79%) had ischaemic stroke, 27 (17%) had intracerebral/subarachnoid haemorrhage, and 6 (4%) experienced cerebral sinus thrombosis. Meta-analyses determined an overall stroke risk of 0.5%, and ischaemic heart disease and requirement for mechanical ventilation were independently predictive of stroke, though the authors do note that the overall stroke risk would be lower if non-hospitalised COVID-19 patients were also included.
Publication date / reference: 01/09/20. Fifi and Mocco. COVID-19 related stroke in young individuals. Lancet Neurol.
Summary: In this comment on Ellul and colleagues’ rapid review ‘Neurological associations of COVID-19’ the authors discuss their own previously reported observations of five COVID-19 patients under the age of 50 presenting with large vessel stroke over a two week period, as well as findings in the literature suggesting stroke patients who tested positive for SARS-CoV-2 are on average younger than uninfected stroke patients. The authors conclude that there is an increasing amount of data suggesting an association between COVID-19 and stroke in young populations that are typically free from vascular risk factors.
Publication date / reference: 17/08/20. Diaz-Perez et al. Acutely altered mental status as the main clinical presentation of multiple strokes in critically ill patients with COVID-19. Neurol Sci.
Summary: The author report on two critically ill patients with COVID-19 in whom acutely altered mental status was the main manifestation of multiple strokes. Following ICU care both patients displayed fluctuating drowsiness, inattention, disorientation, slow or inconsistent speech, and psychomotor agitation. Neuroimaging revealed multiple ischaemic lesions.
Publication date / reference: 06/08/20. Nawabi et al. Clinical and Imaging Characteristics in Patients with SARS-CoV-2 Infection and Acute Intracranial Hemorrhage. J Clin Med.
Summary: A multicentre retrospective, case series (n=18) of patients with SARS-CoV-2 infection and intracranial hemorrhage. The median time of ICH was at 11 days post admission. Isolated cortical subarachnoid haemorrhage was the main ICH seen, and in most cases manifested in rarely reported areas along the convexity of the brain, which is previous reports are most commonly seen in vascular disorders like PRES. The authors postulate that endothelial dysfunction, perhaps as a manifestation of SARS-CoV-2, could be a risk factor for ICH in these populations. Caution is required given that a large proportion of the patients were anticoagulated at the time of the bleeds, and seven patients received ECMO, a known risk factor for ICH.
Publication date / reference: 09/07/20. Ntaios et al. Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry. Stroke.
Summary: International case control study asking whether stroke severity and outcomes differ between patients with and without COVID-19. The authors reported 174 consecutive patients hospitalized with laboratory-confirmed COVID-19 and ischaemic stroke in 28 sites from 16 countries, and matched them with non-COVID-19 stroke patients on a set of prespecified covariates, including demographics (age, sex), stroke risk factors, and ten comorbidities. There was a trend towards higher prevalence of large-artery stroke between the two populations. Stroke patients with COVID-19 had higher risks for severe disability and death compared with stroke patients with non- COVID-19. The authors conclude that COVID-19 associated ischaemic strokes are more severe and call for studies to uncover underlying mechanisms.
Publication date / reference: 12/08/20. Goncalves et al. Thrombotic and Hemorrhagic Neurological Complications in Critically Ill COVID-19 Patients. Neurocrit Care.
Summary: The authors report three patients with acute respiratory distress syndrome (ARDS) and acute renal failure who developed catastrophic intracerebral hemorrhages. They call for randomized clinical trials of anticoagulation strategies.
Publication date / reference: 29/07/20. Kihira et al. Association of Coronavirus Disease (COVID-19) With Large Vessel Occlusion Strokes: A Case-Control Study. AJR Am J Roentgenol.
Summary: Kihira and colleagues present a retrospective case-control study aimed at investigating the association between COVID-19 and stroke subtypes. Of all patients (N=329) who presented with a suspected stroke, 126 of them tested positive for SARS-COV-2. The SARS-COV2 negative patient group (n=203) acted as control. The study found an increased proportion of large vessel occlusion in the covid-19 population compared to control (31.7% vs. 15.3%), the same difference was not found in the small vessel occlusion subtype. Using multivariate analysis, controlling for race and ethnicity, a significant association was found between COVID-19 and large vessel occlusion stroke. Due to its retrospective design, the authors accept that the study is unable to evaluate causality between large vessel occlusion stroke and COVID-19.
Publication date / reference: 06/08/20. Katz et al. Cerebrovascular Complications of COVID-19. Stroke.
Summary: Retrospective case series of COVID-19 patients with imaging confirmed stroke (N=86) during the months of peak pandemic in New York City and Long Island. Logistic regression analysis found COVID -19 to be a strong independent risk factor for in-hospital stroke amongst age, sex, black race, ICH, DVT, AF, Obesity and past stroke/ TIA. Other significant risk factors identified were male and presence of DVT. in addition, the authors found that in this study population the stroke presentations were frequently atypical, that majority presented with non focal deficits (67.4%), instead are multi-vascular territories, with concomitant haemorrhages. It is important to highlight that the study used historical patients as controls, raising the possibility of differences between the control and study group that could not be accounted for (for example the behaviour of hospital staff during the pandemic).
Publication date / reference: 06/08/20. Lapergue et al. Large vessel stroke in six patients following SARS-CoV-2 infection: a retrospective case study series of acute thrombotic complications on stable underlying atherosclerotic disease. Eur J Neurol.
Summary: This is a retrospective study aiming to identify the association between ischemic strokes associated with SARS-CoV-2 infection in 6 patients with underlying atherosclerotic disease. All 6 patients had both intra and extracerebral thrombi, as shown on CT or MR imaging as well as underlying vascular risk factors. 5/6 of these patients had large thrombi in the cervical carotid artery with underlying mild non-stenosing atheroma. 3 of these patients eventually died, while the other 3 were successfully discharged to rehab centres. The authors acknowledge the limitations of a retrospective study – but urge clinicians to be vigilant for new onset of ischemic stroke in patients with vascular risk factors, atherosclerotic disease and concurrent COVID-19.
Publication date / reference: 05/08/20. Agarwal et al. Cerebral Microbleeds and Leukoencephalopahy in Critically Ill Patients With COVID-19. Stroke.
Summary: This study retrospectively examined patient charts of SARS-CoV-2 adults admitted to an academic medical center in New York City. Out of 4131 admitted COVID-19 patients, 115 adults had an MRI of the brain performed. Of these, 35 had cerebral leukoencephalopathy and/or cerebral microbleeds. Of the remaining 80, 47 had acute/chronic infarcts, haemorrhages, or other chronic findings and 33 patients had normal MRI brains. In this cohort, patients with leukoencephalopathy and/or microbleeds were younger and perhaps predominantly male. The odds ratio ‘per day increase’ when being on a ventilator and having leukoencephalopathy and/or cerebral microbleeds was 1.09 (95% CI 1.06-1.12) when compared to not having leukoencephalopathy and/or cerebral microbleeds. The authors concluded that leukoencephalopathy and/or cerebral microbleeds are seen in patients with COVID-19 patients with severe illness marked by prolonged ventilator support and hospitalisation, thrombocytopenia and elevated D-dimer.
Publication date / reference: 31/07/20. Zhang et al. Clinical Course and Mortality of Stroke Patients With Coronavirus Disease 2019 in Wuhan, China. Stroke.
Summary: This case series examined the clinical course and mortality of pre-existing stroke patients with SARS-CoV-2 infection. Forty-nine out of 651 patients with COVID-19 had a pre-existing diagnosis of stroke. Patients with prior stroke were more likely to be elderly (70 vs 55 years). Initial symptoms of COVID-19 included fever (80%), cough (66%), fatigue (36%) and dyspnoea (39%). These symptoms did not differ between stroke and non-stroke patients. However, patients with prior stroke more easily developed ARDS and critical pneumonia. Mortality was higher among stroke patients than among those without stroke (45% versus 9%). The authors concluded that this was the first study examining the clinical course and mortality of COVID-19 in pre-existing stroke patients and urged more intensive surveillance and treatment in such cases.
Publication date / reference: 31/07/20. Majidi et al. Emergent Large Vessel Occlusion Stroke During New York City’s COVID-19 Outbreak: Clinical Characteristics and Paraclinical Findings. Stroke.
Summary: In this retrospective, observational case series, Majidi et al collected data from all patients who presented with emergent large vessel occlusion (ELVO) (N=45) during over a three week period where COVID-19 was at its peak in New York City. They found 53% of patients presented with ELVO tested positive for COVID-19, and that these patients had an unusual demographic and risk factor profile (younger, more likely to be male and less likely to be white). The authors also reported a 2-fold increase in the number of large vessel occlusion patients presenting compared to the same period the previous year. Mindful that the study is limited by small sample size and retrospective design, the study nonetheless highlights importance for clinicians to consider acute ischemic stroke as a presentation of COVID-19, particularly in populations without typical cardiovascular risk factors.
Publication date / reference: 07/08/20. Shahjouei et al. SARS-CoV-2 and stroke characteristics: a report from the multi-national COVID-19 stroke study group. MedRxiv preprint.
Summary: In this preprint multi-national observational case-series study involving 136 tertiary centres in 32 countries, data were collected on SARS-CoV-2 infected adult patients with subsequent imaging-confirmed stroke. A total of 432 cases were included. Among these 74.8% (323/432) had sustained an acute ischaemic stroke, 21.1% (91/432) intracranial haemorrhage, and 4.2% (18/432) cerebral venous or sinus thrombosis. Among acute ischaemic stroke patients 44.5% had large vessel occlusion whilst 10% had small vessel occlusion according to the TOAST criteria. The authors reported a large proportion of young patients and patients without vascular risk factors, with just under a quarter (104/432) of patients being under the age of 55 and a similar proportion (105/432) having no identifiable risk factors. Interestingly a substantial minority of patients (144/380 available) had presented to the hospital with stroke-related symptoms as the major presenting complaint, with asymptomatic or undiagnosed COVID-19.
Publication date / reference: 07/20. Uchino et al. Decline in Stroke Presentations During COVID-19 Surge. Stroke.
Summary: The authors obtained healthcare data from 19 emergency departments in Ohio, USA, in order to establish whether the number of acute stroke presentations had been altered during the COVID-19 pandemic. Variables included total daily stroke alerts, thrombolysis, time to presentation and severity of stroke. Baseline (January 1st – March 8th, 2020) data was compared with COVID-19 period (March 9th – April 2nd, 2020) data. The study reported a significant reduction in daily stroke alerts from the baseline (median 10, IQR 8-13) to COVID period (median 8, IQR 4-10), p=0.001. Other variables such as severity and in-hospital process times did not differ between the periods. The authors comment that this may be as a result of a reduced number of ED visits due to fear of contracting SARS-CoV-2.
Publication date / reference: 25/07/20. Shtaya et al. Comment on “Stroke in patients with SARS‑CoV‑2 infection: case series” from a London hospital experience. J Neurol.
Summary: Correspondence describing a case series of two broad populations: stroke patients who subsequently caught COVID-19 (n=5) and COVID-19 patients who subsequently developed stroke (n=17). The authors discerned a further subpopulation of very severe COVID-19 patients in the latter group. In all groups patients who died tended to have higher CRP. However not all COVID-19 patients were scanned, so the number of cases diagnosed with stroke due to COVID-19 disease may be underestimated.
Publication date / reference: 30/07/20. D’Amore et al. Pressing issues in COVID-19: Probable cause to seize SARS-CoV-2 for its preferential involvement of posterior circulation manifesting as severe posterior reversible encephalopathy syndrome and posterior strokes.AJNR Am J Neuroradiol.
Summary: In this retrospective case series, D’Amore and colleagues collected clinical data regarding patients with COVID-19 (PCR confirmed) who underwent CT, CT angiogram or MRI scans (n=27). In 15 cases, there was evidence of acute pathology with the majority of findings being acute posterior circulation ischaemic haemorrhagic events (n=7). One patient in the cohort presented with PRES evidenced by extensive cerebral oedema alongside haemorrhagic lesions. D’Amore and colleagues speculated that SARS-Cov-2 neurotropism may be a contributory factor in the development of acute haemorrhagic brain injury, with preferential involvement of the posterior circulation. However, this study is limited by its small sample size of patients treated at a single institution.
Publication date / reference: 19/07/20. Aoud et al. Ischemic cerebrovascular diseases in patients with COVID-19. Rev Neurol (Paris).
Summary: Three cases of ischaemic stroke are presented representing 0.83% of the total cohort of SARS-CoV-2 positive testing patients in Saint-Camille hospital in France. The study provides more evidence to support a prothrombotic state in COVID-19, as well as the heterogeneity of clinical and radiological findings in ICD.
Publication date / reference: 26/07/20. Altschul et al. Hemorrhagic presentations of COVID-19: Risk factors for mortality. Clin Neurol Neurosurg.
Summary: This retrospective cohort study (n=5,227) included patients with COVID-19 admitted to one of three major New York hospitals during the pandemic. The study aimed to characterise the incidence, risk for mortality and identify risk factors for mortality in patients presenting with brain haemorrhage and COVID-19. 35/5,227 SARS-CoV-2 patients presented with haemorrhagic stroke. Only four cases underwent surgical management and 16/35 subsequently died. Mortality rates varied between subtypes: Subdural haematoma (SDH) = 6/17, Multifocal intracerebral haemorrhage (MFH) = 2/4, subarachnoid haemorrhage (SAH) = 1/2, Multi-compartmental haemorrhage (MCH) = 5/7 and focal intracerebral haemorrhage (fICH) = 2/5. Patients that died had higher rates of severe COVID-19 on admission, higher rates of heart failure, higher rates of INR >1.7 and mostly spontaneous haemorrhages.
Publication date / reference: 07/20. Dogra et al. Hemorrhagic stroke and anticoagulation in COVID-19. J Stroke Cerebrovasc Dis.
Summary: This cohort study aimed to evaluate the presence of intracranial haemorrhage (ICH) in hospitalised patients with COVID-19, as well as the use of prior anticoagulation. The authors examined neuroimaging reports in 755 patients for evidence of haemorrhage. 33 SARS-CoV-2 positive patients suffered an ICH; 22 received therapeutic dose anticoagulation and three received prophylactic dose anticoagulation prior to ICH discovery. The most frequent reason for initiating anticoagulation was elevated D-dimer levels. Limitations included not comparing anticoagulation use to non-ICH patients. The authors called for more research in order to more effectively balance the risks and benefits of anticoagulation in COVID-19.
Publication date / reference: 10/07/20. Argirò et al. Cerebral hemorrhage related to vein thrombosis in Covid-19 patients in different Italian hospitals: View point for clinical and imaging implications. J Neurol Sci
Summary: In this correspondence, the authors reported six patients with COVID-19 (unclear if PCR-confirmed) and intraparenchymal cerebral hemorrhage related to cerebral vein thrombosis. Heparin (LMWH) was given to five of the patients, at least three days prior to the cerebral haemorrhage diagnosis. The neurological presentation and COVID-19 severity greatly varied across the series, with four patients requiring mechanical ventilation and one patient with no respiratory symptoms, who presented with cerebral haemorrhage. The authors call for more selective use of CT brain imaging in ICU and mechanically ventilated patients to detect subversive acute neurological complications of COVID-19.
Publication date / reference: 14/07/20. Annie et al. Prevalence and Outcomes of Acute Ischemic Stroke Among Patients ≤50 Years of Age With Laboratory Confirmed COVID-19 Infection. Am J Cardiol.
Summary: The authors investigated the incidence and outcomes of acute ischaemic stroke in young adults. They queried the TriNetx Research Network to select patients <50 years of age with laboratory confirmed COVID-19 infection (n=9358, one third of whom were hospitalised with severe symptoms). In this young cohort, the incidence of acute ischemic stroke was 64/9358 (0.7%). Stroke was more likely in an older sub-population of these patients, with more comorbidities including hypertension, diabetes, heart failure, nicotine dependence, COPD, prior stroke, and renal failure. Comparing outcomes in patients who had, versus who did not have stroke, all-cause mortality occurred in 10/64 patients after stroke and 58/9294 patients (0.6%) in the no-stroke cohort. The authors acknowledge that a control arm without COVID-19 would be required to confirm an association between COVID-19 and increased risk of ischemic stroke.
Publication date / reference: 20/07/20. Sparr & Bieri. Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19: A Snapshot in Time. Stroke.
Summary: Callosal infarction is generally rare, but the authors report four such cases presenting to a single New York centre over a two-week period. All patients presented with encephalopathy, and had vascular risk factors that were likely exacerbated by hypoxia, renal failure, inflammation, and coagulopathy caused by COVID-19. The authors argue that a cluster of infarctions isolated to the corpus callosum involving the splenium is distinctly unusual and deserving of further evaluation.
Publication date / reference: 20/07/20. Rothstein et al. Acute Cerebrovascular Events in Hospitalized COVID-19 Patients. Stroke
Summary: In this retrospective observational study Rothstein et al selected hospitalised COVID-19 patients with brain imaging across 3 hospitals in Philadelphia (N=833) and sought to investigate the incidence of ischemic (2.4%) and haemorrhagic stroke (0.9%) in this patient population. The authors found that overall risk of acute cerebrovascular events are relatively low. Majority of those with ischemic stroke were older in age with established vascular risk factors, and it is also notable that 80% of the patients were black. Limited by the small overall number of ischemic (n=20) and haemorrhagic (n=8) patients captured, the authors acknowledged that studies of a larger cohort of stroke patients with COVID-19 is needed to understand the various mechanisms contributing to stroke risk.
Summary: This retrospective cohort study investigated the MRI findings of 16 patients with neurological complications of severe COVID-19. 11 of the 16 cases had punctate foci of abnormal susceptibility signal and eight had more than 10 microvascular lesions. Four of the eight cases with clustered lesions involved the corpus callosum and the other four showed predilection for subcortical and deep white matter. The authors reported that their findings suggest that cerebral microvascular lesions, both ischaemic and haemorrhagic, are common in COVID-19 patients with neurological abnormalities. Hypoxic microvascular injury and endothelial disruption are offered as potential pathogenic mechanisms for microvascular injury in COVID-19. The authors questioned whether tracking serum-based markers of coagulability and hyperinflammatory states could be of value in predicting micro haemorrhage and ischaemia.
Publication date / reference: 15/07/20. Diaz-Segarra et al. COVID-19 Ischemic Strokes as an Emerging Rehabilitation Population: A Case Series. Am J Phys Med Rehabil.
Summary: This is a case series of four patients with COVID-19 (unclear if confirmed) and ischemic stroke. Interestingly, two of the patients were non-critically ill and less than 55 years of age whereas the other two were critically ill, >55 years of age and developed stroke during the course of hospitalisation. This small cohort demonstrates some of the clinical heterogeneity of patients with ischaemic stroke and COVID-19. All patients had elevated ferritin, fibrinogen, CRP, and d-dimer levels – reflecting a prothrombotic state which may have contributed to the development of an ischaemic event. However, the paradoxical increase in prothrombin time in these cases and other reports requires further elucidation. The authors call for improved access to appropriate rehabilitation to maximise recovery in this population.
Publication date / reference: 15/07/20. Degeneffe et al. Acute hemorrhage after intra-cerebral biopsy in COVID-19 patients: a report of 3 cases. World Neurosurg.
Summary: In this correspondence, Degeneffe and colleagues responded to criticism regarding the importance of pre-operative screening in patients with COVID-19 to identify those prone to haemorrhagic complications following neurosurgical interventions. However, the authors disputed the use of viral load (SARS-CoV-2) CSF testing and assessment of anosmia and ageusia as a means of screening patients for haemorrhagic risk. They drew on data regarding the non-specificity of disturbed taste and smell and reports of undetectable CSF viral loads in patients with neurological COVID-19 manifestations.
Publication date / reference: 08/07/20 Liang et al. COVID-19 and Decompressive Hemicraniectomy for Acute Ischemic Stroke. Stroke.
Summary: Case series (n=7) of SARS-CoV-2 patients with large hemispheric strokes who were admitted to a neuroscience ITU for edema monitoring. Four died, three received decompressive hemicraniectomy of which two survived. Although caution should be given to the small retrospective series, the authors argue being infected with the virus should not preclude such an operation.
Publication date / reference: 09/07/20 Hernandez-Fernandez et al. Cerebrovascular Disease in Patients With COVID-19: Neuroimaging, Histological and Clinical Description. Brain.
Summary: Single-centre retrospective cohort study examining patients admitted to hospital with confirmed or likely COVID-19 between 1st March and 19th April (n=1683), of whom 23 developed an acute cerebrovascular event (1.4%). Among these CVD patients there were seventeen ischaemic strokes; ten with large vessel occlusion and six affected in the vertebrobasilar territory. The overall clinical outcome was mostly poor and logistic regression modelling identified age as the only independent prognostic factor.
Publication date / reference: 02/07/20. Gulko et al. Acute common carotid artery bifurcation thrombus: an emerging pattern of acute strokes in patients with COVID-19? AJNR Am J Neuroradiol.
Summary: Correspondence describing two cases in response to a previous case report (Goldberg et al., 2020) that had attributed COVID-19 associated stroke to progression of atherosclerotic disease. Here Gulko et al. propose acute thrombosis in the ipsilateral common carotid artery bifurcation as an alternative explanation, per their two cases. They call for studies to examine this potential cause of acute strokes in the context of COVID-19.
Publication date / reference: 02/07/20. Mohamud et al. Intraluminal carotid artery thrombus in COVID-19: another danger of cytokine storm? AJNR Am J Neuroradiol.
Summary: This is a case series of six COVID-19 patients (mean age 65, five male) with acute ischaemic stroke as a consequence of intraluminal carotid artery thrombus. Vascular risk factors were present in all cases, including hyperlipidemia, diabetes, and/or smoking. Elevated CRP and D-Dimer were reported in all cases, amongst other inflammatory markers. The authors hypothesise that the elevated inflammatory state due to COVID-19 leads to instability and rupture of atherosclerotic plaques, resulting in thrombosis / ischaemic stroke.
Publication date / reference: 02/07/20. Li et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol.
Summary: This is a retrospective cohort study examining clinical features, laboratory findings and outcomes of n=219 COVID-19 patients. Acute ischaemic stroke was observed in ten patients (4.6%) and intracerebral haemorrhage in one (0.5%), with six deaths. Features associated with new-onset CVD were older age, severe COVID-19, diabetes, hypertension, history of CVD, and elevated CRP or D-dimer. Treatments for ischaemic stroke were antiplatelet (n=6; aspirin, clopidogrel) or anticoagulant (n=4; enoxaparin).
Publication date / reference: 02/07/20. Merkler et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol.
Summary: This retrospective study compared the risk of ischaemic stroke in patients attending hospital with COVID-19 to that of a historical control group of patients with influenza. N=31/1916 COVID-19 patients had an acute ischaemic stroke compared to n=3/1486 with influenza. Influenza controls tended to be younger and female, and had fewer vascular risk factors. After adjusting for demographic variables, number of vascular risk factors, and ICU admissions, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (OR= 4.6; 95%CI 1.4-15.7).
Publication date / reference: 05/06/20. Agarwal et al. Intracerebral hemorrhage and SARS-CoV-2: association or causation? Ann Indian Acad Neurol.
Summary: The purpose of this retrospective study was to evaluate if SARS-CoV-2 infection was associated with an increased risk of intracerebral haemorrhage (ICH). The authors analysed medical records of patients admitted to their neurology unit with stroke and found that of n=14 patients with ICH, two tested positive for SARS-CoV-2. The sample size is insufficient to detect a statistically significant association.
Publication date / reference: 25/06/20. Belani et al. COVID-19 Is an Independent Risk Factor for Acute Ischemic Stroke. AJNR Am J Neuroradiol.
Summary: Retrospective case-control study examining whether there is a statistically independent association between COVID-19 and ischemic stroke. Drawing entirely from patients referred for neuroimaging ‘query stroke’ the authors studied n=41 cases with positive scans and n=82 matched controls with negative scans. In this selected population, having COVID-19 increased the odds of a diagnosis of stroke almost four-fold (OR=3.9, 95%CI=1.7-8.9).
Publication date / reference: 24/06/20. D’Anna et al. Characteristics and clinical course of Covid-19 patients admitted with acute stroke. J Neurol
Summary: Correspondence describing a case series of n=8 patients with PCR-positive COVID-19 who were admitted to ICU with stroke (seven ischaemic, one haemorrhagic). The authors propose that early detection of stroke symptoms in Covid-19 patients may allow better identification of those patients who could benefit from reperfusion therapy.
Publication date / reference: 24/06/20 Ashrafi et al. COVID-19-related strokes in adults below 55 years of age: a case series. Neurol.sci.
Summary: Case series of n=6 patients under the age of 55 presenting with neurological symptoms of stroke and admitted to acute stroke unit. 5 out of 6 patients were not known cases of COVID-19, but diagnosis was confirmed later. These patients had no previous history of CVD and all had negative carotid doppler. Most involved area was MCA (n=5). Most patients had low lung involvement score (zonal score based on CT chest scan). Elevated d-dimer was seen in all patients and all had oxygen saturations below 92% on room air. But lung involvement extension appeared unrelated to stroke development.
Publication date / reference: 22/06/20 Immovilli et al. Stroke in COVID-19 patients—A case series from Italy. Int J Stroke
Summary: Case series of n=19 patients with COVID and stroke from a COVID outbreak epicentre in Italy. Retrospective analysis found that incidence of stroke among COVID inpatients was 2.2% at the site. The majority of strokes were ischaemic (17/19, 89.5%) compared to haemorrhagic (2/19, 10.5%). The majority (15/19) had a stroke during COVID illness. Interestingly, an association between stroke and pneumonia severity was found.
Publication date / reference: 16/06/20 Sharifi-Razavi et al. Ischemic Stroke Associated with Novel Coronavirus 2019: A Report of Three Cases. J Int Neurosci.
Summary: Case series (n=3) of patients with ischaemic stroke and concurrent SARS-CoV-2.
Publication date / reference: 11/06/20 Khan et al. COVID-19 and Acute Ischemic Stroke- A Case Series From Dubai, UAE. Int J Stroke.
Summary: Correspondence reporting a case series of n=22 patients with ischaemic stroke and confirmed COVID-19 infection. Most patients were young males, and two thirds had one or more vascular co-morbid conditions. All patients had large territory infarctions, with most having evidence of vessel occlusion on CT angiogram. The authors discuss the concept of COVID-19 associated coagulopathy.
Publication date / reference: 11/06/20 Morelli et al. COVID-19-Related Stroke: Barking Up the Wrong Tree? Eur Neurol.
Summary: Correspondence arguing that it is too early to consider a direct “cause-effect” relationship between 2019-nCoV infection and stroke occurrence, and calling for more prospective large-volume studies.
Publication date / reference: 11/06/20 Franceschi et al. Neurovascular Complications in COVID-19 Infection: Case Series. Am J Neuroradiol.
Summary: Case series of 10 hospitalized patients with confirmed coronavirus 2019 infections who developed severe neurovascular complications, mostly ischemic stroke, and mostly with very poor outcomes.
Publication date / reference: 09/06/20 Cantador et al. Incidence and Consequences of Systemic Arterial Thrombotic Events in COVID-19 Patients. J Thromb Thrombolysis.
Summary: Single-centre retrospective cohort (case note review) study. Of 1419 patients admitted with COVID-19, n=14 (1%) had a systemic arterial thrombotic event, eight of which were in the brain (six ischaemic strokes and two TIAs).
Publication date / reference: 08/06/20 Mehrpour et al. EXPRESS: COVID-19 and stroke in Iran; a case series, and effects on stroke admissions. Int J Stroke.
Summary: retrospective case control study of stroke patients with (n=31) and without (n=99) SARS-CoV-2 infection. Patients with COVID-19 were older had more large vessel and more severe strokes on average.
Publication date / reference: 05/06/20 Malentacchi et al. Concomitant Brain Arterial and Venous Thrombosis in a COVID-19 Patient. Eur J Neurol.
Summary: Case report of an 81-year-old man receiving non-invasive respiratory support, who developed confusion progressing subacutely to coma. CT angiogram suggested partial bilateral MCA occlusions and contrast-enhanced CT showed a filling defect in the right sigmoid sinus. COVID-19 coagulopathy may involve both arterial and venous systems: the authors recommend early neuroradiological investigation where indicated.
Publication date / reference: 05/06/20 Sweid et al. EXPRESS: Brain Ischemic and Hemorrhagic Complications of COVID-19. Int J Stroke.
Summary: Retrospective case series of SARS-CoV-2 confirmed patients with stroke. 17 acute ischemic strokes, three aneurysmal rupture, and two sinus thromboses. COVID-19 strokes were more complicated, due to burden and consistency, plus the involvement of venous and arterial vasculature. Those affected were also younger.
Publication date / reference: 04/06/20 COVID-19 presenting with thalamic haemorrhage unmasking moyamoya angiopathy. Can J Neurol Sci.
Summary: Case of a 19-year-old SARS-CoV-2 positive patient who presented with thalamic stroke and moyamoya angiopathy. Her presentation included cognitive impairment and dystonia.
Publication date / reference: 03/06/20 García-García et al. Haemorrhagic Conditions Affecting the Central Nervous System in COVID-19 Patients. Neurosurgery.
Summary: Case series (n=4) of SARS-CoV-2 positive patients with neurological symptoms and CNS haemorrhage, both typical and atypical.
Publication date / reference: 26/05/20 Zayet et al. Acute Cerebral Stroke With Multiple Infarctions and COVID-19, France, 2020. Emerg Infect Dis.
Summary: Case series (n=2) of coronavirus disease patients in France involving presumed thrombotic stroke that occurred during ongoing anticoagulation treatment for atrial fibrillation stroke prophylaxis; 1 patient had positive antiphospholipid antibodies.
Publication date / reference: 26/05/2020 Venketasubramanian et al. Stroke in COVID-19 and SARS-CoV-1. Cerebrovasc Dis.
Summary: Short article comparing rates of stroke in COVID-19 versus SARS.
Publication date / reference: 25/05/20. Jillella et al. Characteristics of Ischemic Stroke in COVID-19: A Need for Early Detection and Management. MedRxiv (preprint).
Summary: Case series (n=8) of SARS-CoV-2 confirmed patients with ischaemic stroke. The authors report higher than expected rates of cryptogenic stroke in the COVID-19 group (62.5% vs 20% of non-COVID-19 strokes).
Publication date / reference: 22/05/20. Gunasekeran et al. Stroke in a young COVID -19 patient. QJM.
Summary: Case report of 40-year-old female without a past medical history who was intubated due to critical SARS-CoV-2 infection. Whilst in ICU she developed a huge MCA infarct which caused a central diabetes insipidus. She was negative for lupus anticoagulant with no septal defects on echo.
Publication date / reference: 20/05/20 Morassi et al. Stroke in patients with SARS-CoV-2 infection: case series. Journal of Neurology.
Summary: Retrospective case-series (n=6) of ischaemic strokes in cases of confirmed SARS-CoV-2. One was encephalopathic prior to the stroke with focal seizures and behavioural disturbance. All patients saw raised LFTs and LDH, whilst 4 of the patients demonstrated.
Publication date / reference: 19/05/20
Heman-Ackah et al. Neurologically Devastating Intraparenchymal Hemorrhage in COVID-19 Patients on Extracorporeal Membrane Oxygenation: A Case Series. Neurosurgery.
Summary: Retrospective case analysis (n=2) of confirmed SARS-CoV-2 confirmed patients on ECMO (a treatment for severe hypoxia) who suffered massive intracranial bleeds whilst receiving treatment. The authors posit that ECMO can derange clotting cascades, however, there was no such derangement in the patients described in this report.
Publication date / reference: 18/05/20 Merkler et al. Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza. MedRxiv (preprint)
Summary: retrospective cohort study of stroke in patients with SARS-CoV-2 (n=2,132) and influenza (1,516). 1.5% of SARS-CoV-2 had an ischaemic stroke compared with 0.2% of patients with influenza, a 7.5-fold increase. Interestingly 13 (42%) of the strokes in the SARS-CoV-2 group were cardioembolic in origin.
Publication date / reference: 14/05/20 Goldberg et al. Cerebrovascular Disease in COVID-19. American Journal of Neuroradiology.
Summary: Case report of a 64-year-old male with PCR confirmed SARS-CoV-2. Authors describe this as the first case to include imaging at multiple time points and CT angiography.
Publication date / reference: 12/05/20 Hughes et al. COVID-19 and the Cerebro-Cardiovascular Systems: What do we Know so Far? J Am Heart Assoc.
Summary: Detailed review of the shared mechanisms of systemic infection and cerebrovascular disease from coagulopathy in SARS-CoV-19 infection. Summary table of current evidence so far.
Publication date / reference: 12/05/20 Valderrama et al. Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Ischemic Stroke. Stroke (preprint)
Summary: Detailed case report of a 52-year-old man who represented with stroke following SARS-CoV-19 infection. The report provides imaging data on the case, as well as investigation of a potential risk of thrombotic strokes in infection. Authors suggest stroke may be increased due to direct damage to the heart and vascular endothelium, inflammation, and elevation of prothrombotic factors.
Publication date / reference: 11/05/20 Wang et al. Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics. J Neurointerv Surg.
Summary: Case series (n=5) of patients presenting with stroke and concurrent SARS-CoV-2 who underwent thrombectomy. Each patient did have objective coagulopathy on blood tests; however, the authors maintain these are a novel group to treat given their young age (mean 52.8) and a propensity for multiple territory infarcts and high clot burden. For these reasons, successful revascularisation will prove difficult.
Publication date / reference: 06/05/20 Tunç et al. Coexistence of COVID-19 and acute ischemic stroke report of four cases. Journal of Clinical Neuroscience.
Summary: Case series (n=4) of co-diagnosed ischaemic stroke and SARS-CoV-2 (NT PCR confirmed) in patients aged between 45-77. The authors further the existing evidence potentially linking the prothrombotic state seen during infection and cerebrovascular infarcts. It should be noted that each case had independent risk factors for stroke.
Publication date / reference: 05/05/20 Muhammad et al. Letter to editor: Severe brain haemorrhage and concomitant COVID-19 Infection: A neurovascular complication of COVID-19. Brain Behav Immun.
Summary: Case report of aneurysmal rupture in a patient with SARS-CoV-19 infection. Commentary implicating systemic inflammatory responses in endothelial dysfunction and increasing risk of haemorrhage.
Publication date / reference: 03/05/20 Berekashvili et al. Etiologic Subtypes of Ischemic Stroke in SARS-COV-2 Virus patients. medRxiv (preprint)
Summary: Case series (n=10) of ischaemic strokes in patients with SARS-CoV-19 with varying aetiologies (ages 27-75). There were no common risk factors for stroke in a fifth of patients.
Publication date / reference: 01/05/20 Garaci et al. Venous Cerebral Thrombosis in COVID-19 Patient. Journal of Neurological Sciences.
Summary: Authors report the case of a 44-year-old female with no comorbidities who developed a cerebral venous thrombosis as well as thromboses of the superior vena cava and pulmonary artery. She developed these 2 weeks following a positive nasopharyngeal swab for SARS-CoV-2. Her bloods demonstrated a disseminated intravascular coagulopathy (DIC).
Publication date / reference: 01/05/2020 González-Pinto et al. Emergency Room Neurology in times of COVID-19: Malignant Ischemic Stroke and SARS-COV2 Infection. Eur J Neurol.
Summary: Single case report of a 36-year-old health care worker who suffered left MCA infarct in the context of a COVID-19 infection.
Publication date / reference: 30/04/2020 Beyrouti R, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry.
Summary: Case series (n=6) of consecutive patients with acute ischaemic stroke and COVID-19 including demographic, clinical, radiological and laboratory characteristics(♦).
Publication date / reference: 30/04/2020 Al Saiegh et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry.
Summary: Case series (n=2) with confirmed covid-19 on nasopharyngeal swab but not in CSF. Patient one developed a aneurysmal subarachnoid haemorrhage and patient two developed an ischaemic stroke with massive haemorrhagic conversion.
Publication date / reference: 29/04/20 Hughes et al. Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19. Eur J Case Reports Internal Medicine.
Summary: Detailed case report of CVST as a presenting symptom of COVID-19 infection.
Publication date / reference: 28/04/2020 Avula A et al. COVID-19 presenting as stroke. Brain Behav Immun.
Summary: Case series of four patients presenting with imaging confirmed acute strokes and PCR confirmed SARS-CoV-2 infection.
Publication date / reference: 28/04/2020 Oxley TJ et al. Large-Vessel Stroke as a Presenting Feature of COVID-19 in the Young. N Engl J Med.
Summary: Case series (n=5) of large-vessel stroke in patients younger than 50 diagnosed with SARS-CoV-2
Publication date / reference: 23/04/2020 Zhang Y et al. Coagulopathy and Antiphospholipid Antibodies in Patients with COVID-19. N Engl J Med.
Summary: Case series (n=3) of stroke (as well as additional infarcts) positive for COVID-19 and antiphospholipid antibodies.
Publication date / reference: 23/04/2020 Lodigiani et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis Research.
Summary: Prospective observational study of 288 patients with confirmed COVID-19. Ischaemic stroke was diagnosed in 9 (2.5%) of included patients.
Publication date / reference: 23/04/2020 Lushina N, et al. Pulmonary, Cerebral, and Renal Thromboembolic Disease Associated with COVID-19 Infection. Radiology.
Summary: Single case report of 84-year-old man with thrombotic occlusion of the distal basilar artery concurrent with COVID-19 infection.
Publication date / reference: 21/04/2020 Moshayedi P et al. Triage of Acute Ischemic Stroke in Confirmed COVID-19 : Large Vessel Occlusion Associated With Coronavirus Infection. Front Neurol.
Summary: Single case report of an elderly patient with multiple infarctions (STEMI, ischaemic limbs) who subsequently developed left middle cerebral artery infarct in the context of COVID-19 infection.
Publication date / reference: 20/04/2020 Morassi, M et al. Cerebrovascular complications in patients with SARSCoV- 2 infection: Case series. Research Square.
Summary: Case series of six patients (4 ischaemic stroke, 2 haemorrhagic stroke). CT/MRI demonstrated probable thromboembolic ischaemic strokes in 2, ischaemic strokes in 2 and haemorrhage in 2. All RT-PCR positive in nasopharyngeal swabs.
Publication date / reference: 20/04/2020 Aggarwal G, et al. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke.
Summary: Meta-analysis of 4 studies showing 2.5-fold increase in OR of severe COVID-19 in patients with history of stroke. No statistically significant association of stroke with mortality in patients with COVID-19 infection.
Publication date / reference: 10/04/2020 Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res.
Summary: Case series of three patients with ischaemic stroke. CT brain was performed in all cases, but no details given. Authors stats “Proven COVID-19”, but details not reported.
Publication date / reference: 01/04/2020 Zhai P, et al. The impact of COVID-19 on ischemic stroke: A case report. Preprint (Research Square).
Summary: Single case report of 79 year old male diagnosed with acute ischemic stroke (lacunar infarction on CT imaging) presenting with right sided weakness. COVID-19 positive.
Publication date / reference: 13/03/2020 Li, Y. et al. Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study. Preprint (SSRN/Lancet).
Summary: Case series (n=221) of patients with COVID-19. 11 (5%) developed acute ischemic stroke, 1 (0·5%) cerebral venous sinus thrombosis (CVST), and 1 (0·5%) cerebral haemorrhage
Publication date / reference:27/03/2020 Sharifi-Razavi A et al. COVID 19 and Intra cerebral hemorrhage: Causative or Coincidental. New Microbes New Infect.
Guillain-Barré Syndrome (GBS) and variants
Publication date / reference: 18/04/2021 Sheikh AB et al., Association of Guillain-Barre syndrome with COVID-19 infection: An updated systematic review. J Neuroimmunol.
Summary: The authors of this systematic review investigated the link between Guillain Barre syndrome (GBS) development as a result of COVID-19 infection. Following analysis of 64 relevant studies, the mean age of patients was established at 56 ± 16 years. The majority of those affected were males (64.9%). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for diagnosis of the majority of patients (69.2%). Paresthesia was the most prevalent symptom (with 48.9% of patients affected); and whilst most patients recovered, a minority of patients (4.26%) later presented with facial diplegia. Acute inflammatory demyelinating polyneuropathy (AIDP) was linked with higher levels of glucose on CSF analysis and reduced paresis. 77.7% of patients received immunoglobulin therapy (IVIg). AIDP patients were more likely to receive IVIg therapy and, thus, develop respiratory complications.
Publication date / reference: 03/04/2021 González del Castilo et al., Currently available data regarding the potential association between COVID-19 and Guillain-Barré syndrome Brain
Summary: This study forms part of the Unusual Manifestations of Covid-19 (UMC-19) project, a retrospective, case-controlled, emergency department-based, multicentre study investigating the potential relationship between COVID and 10 different entities that could be influenced by SARS-Cov-2 infection. This study showed that GBS is rarely observed as a form of COVID-19 presentation. However, in comparison with non-COVID-19 patients coming to the emergency department, patients with COVID presented a significantly higher relative frequency of GBS.
Publication date / reference: 12/03/2021. Moure et al. Acute Polyneuropathy in an Outpatient Context During the SARS-CoV-2 Pandemic: A Brief Case Serie Report. SN Compr Clin Med.
Summary: This is a case series of five patients with mild COVID-19 who manifested neurological symptoms consistent with acute polyneuropathy (confirmed with neurophysiological studies). Interestingly, not only was the COVID-19 disease mild in these patients, but the neurological deficits were also self-limiting. The patients only required outpatient care and symptoms resolved in all cases.
Publication date / reference: 10/3/2021 Li et al. Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID-19-associated Guillain-Barré syndrome. Cell Prolif.
Summary: This study aimed to delineate the potential genetic crosstalk between COVID-19 and GBS using bioinformatic analyses. The authors found that COVID-19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein-protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID-19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA-DRB1, HLA-DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID-19 and GBS further demonstrated the activation of interleukin-17 signalling in both conditions. They concluded that aberrant Th17 cell differentiation as a possible mechanism by which COVID-19 can increase the risk of GBS.
Publication date / reference: 13/03/2021 Umapathi et al. Guillain-Barré syndrome decreases in Singapore during the COVID-19 pandemic. J Peripher Nerv Syst.
Summary: This paper from Singapore presents further data suggesting that COVID-19 may not be a significant antecedent infection of GBS. During the covid-19 outbreak in the country in 2020, in comparison to 2019, there was a halving of presentations of GBS (9/month to 4/month). There was also no association between cases of GBS and patient’s covid-19 status.
Publication Date/Reference: 09/10/2020 Sriwastava et al. Guillain-Barré Syndrome and its variants as a manifestation of COVID-19: A systematic review of case reports and case series. J Neurol Sci
Summary: This is among the initial reports that systematically reviewed GBS and its variants for clinical presentation, outcomes and neurological complications. GBS variants like Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP), Acute Motor Sensory Axonal Neuropathy (AMSAN) and Acute Motor Axonal Neuropathy (AMAN) and rare variants like Miller Fisher Syndrome and Bilateral facial Palsy with paresthesia, among others were included. 66% of the patients had AIDP and 34% had non-AIDP variants of GBS. The modified Erasmus GBS Outcome Score (mEGOS) – a prediction model for estimating the probability of walking independently in first six months of follow up – was determined and wasn’t significantly different for AIDP and AMSAN/AMAN patients. Majority of the patients in both sub-groups belonged to Brighton Level 1 indicative of certainty of the diagnosis.
Publication Date/Reference: 09/12/2020. Fragile et al. Incidence, clinical characteristics, risk factors and outcomes of Guillain-Barré syndrome in patients with Covid-19. Ann Neurol.
Summary:In this retrospective case-control study, which included 61 emergency department centers in Spain, Fragiel et al. focused on the incidence of Guillen-Barre Syndrome (GBS) in patients with COVID-19 and reported that among 71,904 patients, 11 had GBS (0.015%), which was higher than non-COVID-19 (0.002%) patients (OR=6.30, 95%CI=3.18-12.5), with standardised incidence (9.44 and 0.69 cases/100,000-year, respectively, OR=13.5; 95%CI=9.87-18.4). Olfactory-gustatory disorders and admission to intensive care were more frequent in COVID-GBS than non-COVID-GBS patients; however the two groups did not significantly differ in terms of mortality.
Publication date / reference: 14/11/2020. Abolmaali et al. Guillian-Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series. J Clin Neurosci.
Summary: Three cases of GBS during the active phase of COVID-19 were reported, with GBS leading to death in one 47 year old male patient on day four of admission. The authors recommend testing for COVID-19 in patients presenting with GBS.
Publication Date/Reference: 06/11/20. Filosto et al. Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions. J Neurol Neurosurg Psychiatry.
Summary: This multicentre retrospective study examined the incidence of Guillain-Barré syndrome (GBS) during the COVID-19 pandemic and compared this to the same time period (March and April) in 2019. Previously, case reports and case series had identified GBS as a potential consequence of SARS-CoV-2 infection. This study aimed to further explore the connection. Within 12 Italian referral hospitals, 34 diagnoses of GBS were made during March-April 2020. During the same time period in 2019, 13 diagnoses were made. Out of the 34 cases of GBS during the pandemic, 30 (88.2%) had confirmed positive SARS-CoV-2 infection. The authors estimated the incidence of GBS in COVID-19 patients during the pandemic as 2.14/100,000/year, while in 2019, the incidence was 0.93/100,000/year. Therefore the relative incidence in March and April compared to 2019 was 2.6. Within the SARS-CoV-2 positive GBS patients, 90% presented with a classical form of GBS and the interval between COVID-19 onset and neuropathic symptoms was 24.2 (SD=1.81) The authors concluded that their findings further supported a pathogenic link between COVID-19 and GBS and presented direct viral damage and immune function dysregulation as possible hypotheses.
Publication Date/Reference: 16/09/20. Satyan Nanda et al. Covid-19 associated Guillain-Barre Syndrome: Contrasting tale of four patients from a tertiary care centre in India. Am J Emerg Med.
Summary: This communication report details four cases of COVID-19 who presented to hospital with features in keeping with Guillain-Barre Syndrome.
Publication date / reference: 02/10/2020. Gigli et al. HLA and immunological features of SARS-CoV-2-induced Guillain-Barré syndrome. Neurol Sci.
Case report of a 53 year old man who developed GBS 2 months following COVID-19. CSF analysis showed increased CSF concentration of IL-8, and moderately increased serum levels of IL-6, IL-8, and TNF-α. This patient also carried several HLA alleles known to be associated with GBS, including distinctive class I (HLA-A33) and class II alleles (DRB1*03:01 and DQB1*05:01). To the best of the authors’ knowledge, this is the first case of GBS in which SARS-CoV-2 antibodies were detected in the CSF.
Publication date / reference: 01/10/20. Fatehi et al. Acute Ischemic and Hemorrhagic Stroke and COVID-19: Case Series. SN Compr Clin Med.
Fatehi and colleagues report a case series of five patients with COVID-19. All patients presented with fever, chills, muscular pain, cough and tachypnea were present in all patients. All patients had a erythrocyte count and abnormal findings present on CT scans of the brain. The authors promote that COVID-19 may cause blood vessel damage and lead to stroke.
Publication date / reference: 02/09/20. Garnero et al. COVID-19-related and not related Guillain-Barré syndromes share the same management pitfalls during lock down: The experience of Liguria region in Italy. J Neurol Sci.
Summary: The authors compared the clinical characteristics and course of GBS patients with COVID-19 (n=6) and without COVID-19 (n=9), presenting to their Italian hospital during the height of the pandemic. Five of the COVID-19 patients also had pneumonia. Outcomes in this very small case series were severe: one COVID-19 associated case died and another two remained quadriplegic and ventilator-dependent in ICU at one month followup.
Publication date / reference: 11/09/20. Trifan et al. Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex. J Stroke Cerebrovasc Dis.
Summary: This retrospective study of patients with acute stroke with COVID-19 aimed to describe the characteristics of a diverse cohort of acute stroke patients. The study included 83 patients, 47% of which were black, 28% hispanics and 16% whites. The median age of the included patients was 64 years. Approximately 89% had at least one pre-existing vascular risk factor. The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalisation (73% vs. 49%; p=0.04). By stroke subtype, 77% were ischaemic, 19% were intracerebral hemorrhage and 3% were subarachnoid haemorrhages. Compared with females, males had a higher mortality (38% vs. 13%; p=0.02) and were less likely to be discharged home (12% vs. 33%; p=0.04). The authors concluded that in this cohort of SARS-CoV-2 infected stroke patients, severe in-hospital complications and worse outcomes after ischaemic strokes were higher in males than in females.
Publication date / reference: Preprint 24/07/20. Keddie et al. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barre syndrome. Preprint MedRxiv
Summary: This epidemiological and cohort study sought to investigate a causative association between COVID-19 and Guillain-Barré syndrome (GBS). Cases reported via the UK National Immunoglobulin Database between 2016-2019 were studied and compared to case reports published during the pandemic. Also, the clinical features, investigations and outcomes were compared between COVID-19 probable (n=12), confirmed (n=13), and negative (n=22) cases reported by members of the British Peripheral Nerve Society. GBS and COVID-19 incidence varied by region and did not correlate (r=0.06, 95%CI -0.56, p=0.86). Interestingly, fewer cases of GBS were reported during March, April and May compared to previous years. No significant differences were found in the pattern of weakness, time to nadir, neurophysiology or outcomes between case groups. The authors concluded that their evidence did not point to SARS-CoV-2 as a causative agent of GBS.
Publication date / reference: 14/07/20. Manganotti et al. Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain Barré syndrome and polyneuritis cranialis in COVID-19 patients: a case series. J Med Virol.
Summary: the authors reported a case series (n=5) of patients with GBS following COVID-19 disease. The onset of neurological symptoms included polyradiculoneuritis and cranial polyneuritis (including facial nerve involvement). Serum interleukins (IL-6 and IL-8) were significantly raised in three patients, and the authors argue that the observed polyneuropathy should be considered as part of a cytokine storm syndrome. The authors propose that facial nerve involvement, in the demyelinating process, could underlie the observed ageusia in this report.
Publication date / reference: 23/06/20. Tatu et al. Guillain-Barré syndrome in the COVID-19 era: another occasional cluster? J Neurol.
Summary: Correspondence reporting a small but unusually clustered case series (n= 7) of patients admitted with GBS to two hospitals in France and Switzerland. As with a similar prior study in Italy, all patients were PCR negative for SARS-CoV-2. The authors speculate about possible mechanistic explanations including false negative PCR results, or/and a cryptic immunological response to
Publication date / reference: 16/06/20 Ahmad and Rathore. Guillain Barre syndrome in COVID-19:A scoping review. MedRxiv (preprint).
Summary: review up to the 18th of May of 24 cases of GBS. The authors provide a thorough review of the clinical and electrophysiological findings in SARS-CoV-2 positive GBS patients to date.
Publication date / reference: 11/06/20 Manganotti et al. Miller Fisher syndrome diagnosis and treatment in a patient with SARS-CoV-2. J Neurovirol.
Summary: Case report of a 50-year-old woman admitted to hospital with SARS-CoV-2 pneumonia. Ten days after admission she developed ophthalmoplegia, ataxia, and areflexia, and was treated with IVIG for Miller Fisher syndrome. It resolved one week after starting treatment.
Publication date / reference: 09/06/20 Sancho-Saldana et al. Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection. Clin Med (Lond).
Summary: Case report of a 56-year-old lady developing Guillain-Barré syndrome following severe SARS-CoV-2) infection, in association with leptomeningeal enhancement. She was treated with intravenous immunoglobulin and improved over 2 weeks. The authors speculate that leptomeningeal enhancement could be a marker of GBS in association with SARS-CoV-2 infection.
Publication date / reference: 05/06/20 Reyes-Bueno et al. Miller-Fisher Syndrome After SARS-CoV-2 Infection. Eur J Neurol.
Summary: case report of a 51-year-old female diagnosed with Miller-Fisher Variant of GBS two weeks after SARS-CoV-2 infection.
Publication date / reference: 04/06/20 Oguz-Akarsu et al. Guillain-Barré Syndrome in a Patient with Minimal Symptoms of COVID-19 Infection. Muscle Nerve.
Summary: Case report of a 53-year-old woman with progressive weakness and numbness of her lower extremities. She had a low-grade fever, but no other symptoms of COVID-19. She was SARS-CoV-2 positive on nasopharyngeal swab.
Publication date / reference: 01/06/20 Lascano et al. SARS-CoV-2 and Guillain-Barré Syndrome: AIDP Variant with Favourable Outcome. Eur J Neurol.
Summary: Case series (n=3) of patients with SARS-CoV-2 who presented with distal paraesthesia and rapidly progressive limb weakness. NCS showed a classic demyelinating pattern.
Publication date / reference: 29/05/20 Chan et al. Guillain-Barré syndrome with facial diplegia related to SARS-CoV-2 infection. Can J Neuro Sci.
Summary: Case report of a 58-year-old otherwise healthy male who presented with acute-onset bilateral facial weakness, dysarthria, and paraesthesia in his feet. His lower limb reflexes were absent. He was SARS-CoV-2 swab positive but had no respiratory symptoms.
Publication date / reference: 28/05/20 Andrea et al. New clinical manifestation of COVID-19 related Guillain-Barré syndrome highly responsive to intravenous immunoglobulins: two Italian cases. Neurol Sci.
Summary: Case series of (n=2) of two COVID-19 related GBS. One of GBS/Miller-Fisher overlap, the other an Acute Motor Sensory Axonal Neuropathy with whole body impairment. In both cases, patients were highly responsive to IVIG. CSF for SARS-CoV-2 was negative in both cases.
Publication date / reference: 28/05/20. Lantos et al. COVID-19-Associated Miller Fisher Syndrome: MRI Findings. AJNR Am J Neuroradiol.
Summary: Case of COVID-19-associated Miller Fisher syndrome with MR imaging. Antibody testing was testing was negative for anti-GQ1b.
Publication date / reference: 27/05/2020 Bigaut et al. Guillain-Barré Syndrome Related to SARS-CoV-2 Infection. Neurol Neuroimmunol Neuroinflamm.
Summary: Case series of 2 patients exhibiting demyelinating form of Guillain-Barré syndrome (GBS)
Publication date / reference: 26/05/2020 Fernández-Domínguez et al. Miller-Fisher-like Syndrome Related to SARS-CoV-2 Infection (COVID 19). J Neurol.
Summary: Case report of a patient admitted for impaired gait after SARS-Cov2 infection. MRI head showed non-pathological alterations and CSF SARS-CoV-2 PCR was also negative.
Publication date / reference: 26/05/2020 Riva et al. Post-infectious Guillain-Barré Syndrome Related to SARS-CoV-2 Infection: A Case Report. J Neurol.
Summary: Case report of GBS; SARS-CoV2 on CSF tested negative.
Publication date / reference: 26/05/20 Su et al. SARS-CoV-2 Associated Guillain-Barre Syndrome with Dysautonomia. Muscle and Nerve.
Summary: 72-year-old male with SARS-CoV-2 and quadriplegic GBS and dysautonomia following mild diarrhoea. Weakness presented 6 days after diarrhoea, at no point had he had fever or respiratory symptoms. After initial treatment for GBS he developed fluctuating blood pressures and tachycardia.
Publication date / reference: 19/05/2020 Gigli et al. Guillain-Barré syndrome in the COVID-19 era: just an occasional cluster?Journal of NeurologyJournal of Clinical Neurosciences
Summary: Review of a cluster of GBS cases in a specialist neurology centre during the peak Italian SARS-CoV-2 pandemic. The authors argue an increase from the usual rates of GBS could be linked to the pandemic.
Publication date / reference: 15/05/20 Ghiasvand et al. Symmetrical Polyneuropathy in Coronavirus Disease 2019 (COVID-19). ID Cases.
Summary: Case report of a 68-year-old female who developed bilateral ascending limb weakness on day 3 of her admission due to SARS-CoV-2 infection. This progressed to breathing compromise and she did not survive intubation.
Publication date / reference: 14/05/2020 CCaamaño & Beato. Facial diplegia, a possible atypical variant of Guillain-Barré Syndrome as a rare neurological complication of SARS-CoV-2.Journal of Clinical Neurosciences
Summary: case report of 61-year-old male with no previous neurologic morbidity presenting with facial diplegia ten days after PCR confirmed SARS-CoV-19 infection. The authors propose this could be a rare variant of GBS.
Publication date / reference: 12/05/20 Pfefferkorn et al. Acute polyradiculoneuritis with locked-in syndrome in a patient with Covid-19. J Neurol.
Summary: Case report of a 51-year-old male who developed extensive polyradiculoneuritis leading to a locked-in syndrome. The patient developed generalized nerve root contrast enhancement on MRI suggestive of parainfectious Guillain-Barré-syndrome (GBS). CSF revealed mild pleocytosis (9 cells/μl), normal protein content and negative PCR testing for SARS-CoV-2. Serum anti-ganglioside antibodies were negative.
Publication date / reference: 11/05/20 Arnaud et al. Post SARS-CoV-2 Guillain-Barré syndrome. Clinical Neurophysiology
Summary: Case report of a 64-year old with confirmed SARS-CoV-2. Three weeks later he presented with 4 days of progressive lower limb weakness. His CSF showed markedly raised protein, but no presence of SARS-CoV-2.
Publication date / reference: 12/05/20 Ottaviani et al. Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital. Neurological Sciences.
Summary: Case report of a 66-year-old female who developed rapidly progressive flaccid paralysis with unilateral facial neuropathy after 10 days of mild respiratory symptoms. CSF demonstrated no SARS-CoV-2 but was consistent with GBS. During her ITU stay she experienced transient episodes of confusion with psychomotor agitation(♦).
Publication date / reference: 10/05/20 Scheidl et al. Guillain-Barre syndrome during SARS-CoV-2 pandemic: a case report and review of recent literature. J Peripher Nerv Syst.
Summary: Case report of a 54-year-old female who developed features of acute demyelinating inflammatory polyneuropathy (AIDP) three weeks post SARS-CoV-2 positive PCR.
Publication date / reference: 08/05/20 Marta-Enguita J et al. Fatal Guillain-Barre syndrome after infection with SARS-CoV-2. Neurología (English Edition).
Summary: Case report of fatal clinically diagnosed GBS concurrent with COVID-19 infection. Authors acknowledge that the main limitation of their report is lack of diagnostic tests supporting the diagnosis: neurophysiology and ganglioside antibodies are not reported.
Publication date / reference: 30/04/20 Alberti et al. Guillain-Barre syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm.
Summary: Single case report of a 71-year-old man who developed symptoms suggestive of GBS. As with some other reports, nasopharyngeal swab was positive for COVID-19 however CSF was negative for the virus.
Publication date / reference: 28/04/20 Coen M et al. Guillain-Barré Syndrome as a Complication of SARS-CoV-2 Infection. Brain Behav Immun.
Summary: Case report of an elderly man who presented with paraparesis, distal allodynia, difficulties in voiding and constipation. Nerve conduction studies suggested a demyelinating polyneuropathy. He tested positive for SARS-CoV-2 before the first signs of polyneuropathy, thus supporting a postinfectious GBS phenotype.
Publication date / reference: 24/04/20 Padroni, M et al. Guillain-Barré syndrome following COVID-19: new infection, old complication? J Neurol.
Summary: Single case report of GBS in a 70-year-old with confirmed COVID-19 on nasopharyngeal swab
Publication date / reference: 18/04/20 Virani, A et al. Guillain-Barré Syndrome associated with SARS-CoV-2 infection. ID Cases.
Summary: Single case report of progressive, ascending weakness associated with COVID-19 infection. Note patient had concurrent diarrhoeal illness too.
Publication date / reference: 17/04/20 Gutiérrez-Ortiz, C et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology.
Summary: Case series (n=2) of patients with COVID-19 presenting acutely with Miller Fisher syndrome and polyneuritis cranialis.
Publication date / reference: 17/04/20 Toscano, G et al. Guillain–Barré Syndrome Associated with SARS-CoV-2. N Engl J Med.
Summary: Case series (n=5) of Guillain–Barré syndrome after the onset of COVID-19. Four had a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome.
Publication date / reference: 15/04/20 Camdessanche, J.P et al. COVID-19 may induce Guillain–Barré syndrome. Revue Neurologique.
Summary: Single case report of GBS in a 64-year-old with confirmed COVID-19 on nasopharyngeal swab.
Publication date / reference: 14/04/20 Sedaghat, Z et al. Guillain Barre syndrome associated with COVID-19 infection: A case report. J Clin Neurosci.
Summary: Single case report of 65-year-old male patient with progressive symmetric ascending quadraparesis, diagnosed as Guillain-Barré syndrome
Publication date / reference: 01/04/20 Zhao, H et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol.
Anosmia and dysgeusia
Publication date / reference: 31/04/2021 Amérigo et al. High Frequency of Smell and Taste Dysfunction in Health Care Professionals With COVID-19 Working in Allergy Departments. J Investig Allergol Clin Immunol.
Summary: The authors aimed to assess smell and taste dysfunction, STD in health care professionals with COVID-19, using an online survey to find associations with STD. Of 234 respondents with COVID-19, 74.4% reported STD and 95.6% had ‘moderate-severe impairment’. Being over 55 was associated with fever, anorexia and a longer STD recovery time, but a lower frequency of headache. They conclude STD is a frequent manifestation of COVID-19, typically affecting younger individuals, and dysgeusia may imply more systemic involvement in COVID-19-positive HCPs.
Publication date / reference: 20/04/21 Biadsee et al. Eight-month follow-up of olfactory and gustatory dysfunctions in recovered COVID-19 patients. Am J Otolaryngol.
Summary: This study assessed the prevalence of persistent olfactory impairment in 65 patients eight months post non-hospitalised covid-19. Via self-reported questionnaire, only 52% reported full recovery of olfactory function (the remaining 48% had at least partial recovery). Usual limitations of self-report apply, however this non-recovery rate is high.
Publication date / reference: 20/04/2021 Tsivgoulis et al. Hypothyroidism is associated with prolonged COVID-19-induced anosmia: a case-control study. J Neurol Neurosurg Psychiatry.
Summary: This case-control study aimed to compare the prevalence of hypothyroidism in patients with prolonged COVID-19-induced hyposmia/anosmia versus age- and sex-matched patients with COVID-19 without olfactory disorders. The authors evaluated (n=12) cases with prolonged anosmia/hyposmia (25% men, median age 45 years)(as the only lingering symptom of COVID-19, along with taste disorders in seven patients) and 24 controls (38% men, median age 48 years). A medical history of hypothyroidism had a higher prevalence (50%). All subjects with hypothyroidism had a medical history of autoimmune thyroiditis, treated with oral levothyroxine supplementation. After adjusting for potential confounders (age and sex), hypothyroidism was independently associated with higher likelihood of persistent olfactory dysfunction among patients with COVID-19. They concluded that the findings support an intriguing hypothesis. SARS-CoV-2-induced smell dysfunction could be triggered by a direct viral insult of both the olfactory nerve and the thyroid gland.
Publication date / reference: 13/04/2021 Rebholz et al. Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence. Am J Otolaryngol.
Summary: This study utilised self-administered smell tests to 70 patients an average of four months after confirmed covid-19 in comparison to a control group. The covid-10 group had poorer accuracy in detecting smells, but only by around 10% in comparison to controls. Particular smells such as strawberry, soap, and lemon were poorly identified by the covid-19 group.
Publication date / reference: 4/2021. Bax et al. Hyposmia and Dysgeusia in COVID-19: Indication to Swab Test and Clue of CNS Involvement. Neurol Clin Pract.
Summary: Bax and colleagues interviewed a cohort of 93 patients who were admitted to a non-intensive COVID-19 unit, who had PCR-confirmed SARS-Cov-2 infection. Olfactory and gustatory impairment was present in 58 patients. Where this was present, this preceded systemic systems in 22.4% of cases. Total leukocyte and neutrophil count was found to be 23% and 29% lower in patients with olfactory impairment, respectively.
Publication date / reference: 14/04/2021 Pirker-Kees et al. Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results. Dement Geriatr Cogn Disord.
Summary: In this paper the authors correlate two known neuropsychiatric complications of covid-19 – anosmia and cognitive impairment – and find associations between the two in seven patients versus controls. They suggest the former symptom may be used to predict the latter, but this tiny correlative study is insufficient to make this conclusion.
Publication date / reference: 06/04/2021 Otte et al. Persisting olfactory dysfunction improves in patients 6 months after COVID-19 disease. Acta Otolaryngol.
Summary: This study aimed to investigate how many patients with olfactory function impairment, which was detected in a validated olfactory test 3 months after COVID-19 disease, showed improvement in olfactory function after 6 months. The authors included (n=26) patients with a PCR-confirmed, former COVID-19 disease, with an impaired olfactory function after three months. The olfactory function was evaluated with the sniffing sticks test, the taste function with taste sprays. They found that smelling function improved in all but one patient (96%). All measured subitems, i.e. olfactory threshold, identification and discrimination of odours significantly improved. In the whole mouth taste test all patients showed normal taste function. They concluded that 6 months after COVID-19 disease, olfactory function improves in just about all patients.
Publication date / reference: 04/04/2021 Sehnanobish et al. COVID-19-induced anosmia and ageusia are associated with younger age and lower blood eosinophil counts. Am J Rhinol Allergy.
Summary: The authors of this case-control study aimed to identify associations with anosmia and ageusia amongst patients with COVID-19 (n=486) compared to a control group without COVID-19 (n=103). Data was collected using self-report questionnaire and past medical history obtained from healthcare records. Younger patients were significantly more likely to have anosmia )OR 0·98, 95%CI:0-97-0·99, p = 0·003) and ageusia (OR 0·98, 95%CI:0·97-0·99, p = 0·005). Eosinophil count was also significantly related to anosmia and ageusia. The authors found that these symptoms were associated with a lower eosinophil count OR for anosmia per 0.1-K/μL increase in eosinophils: 0·02, 95%CI:0·001-0·46, p = 0·01, for ageusia 0·10, 95%CI:0·01-0·97, p = 0·047. These results provide insight into potential biomarkers for these neurological sequellae of COVID-19; more research is needed.
Publication date / reference: 31/03/2021 Schwab et al. Sustained Chemosensory Dysfunction during the COVID-19 Pandemic. ORL J Otorhinolaryngol Relat Spec.
Summary: The aim of this study was to investigate the duration of olfactory, gustatory and trigeminal dysfunction in patients in people after 27th February when the first COVID-19 case was confirmed in Denmark. Participants with confirmed and unknown COVID-19 status filled in a baseline online questionnaire on subjective chemosensory dysfunction after 2 months of CD onset. Patients who had not fully recovered could fill-in three found follow-up questionnaires every 6 weeks. Overall 467 patients filled in the questionnaire, of which 401 had combined olfactory and gustatory dysfunction, 31 had isolated olfactory and 31 had isolated gustatory dysfunction. After a mean follow-up of 94.5 days. 82.6% (360/436) of participants reported olfactory improvement and 86.7% (360/436) reported gustatory improvement (376/436). Full recovery was reported in 43.8% (191/436) and 55.0% (240/436) of patients.
Publication date / reference: 22/03/2021 Coelho et al., Clinical and Electrophysiological Outcome Measures of Patients With Post-Infectious Neurological Syndromes Related to COVID-19 Treated With Intensive Neurorehabilitation. Am J Otolaryngol.
Summary: This prospective longitudinal study investigated chemosensory changes in COVID-19 patients and effects 6 months later (n=322) via survey. 96% of respondents reported an impact on QOL at 6 months; 43% self-reported depression. The study population were mostly female (80.4%) with a mean age of 41.6. 67% of patients reported smell alterations beyond 6 months. The paper raises that long-term chemosensory changes can impact not only quality of life but also safety.
Publication date / reference: 26/3/21 Pasquini et al. Testing olfactory dysfunction in acute and recovered COVID-19 patients: a single centre study in Italy. Neurol Sci.
Summary: This cross-sectional, case-control study included 25 patients hospitalised with COVID-19 at the time of data collection and non-matched controls (n=26) comprising recovered patients. Median time from symptom onset to olfactory dysfunction was 33 days in the acutely ill group and 122 days in the recovered group. Olfaction was tested using a 33 item test; the Italian Olfactory Identification Test. Acute illness group had significantly more errors on the olfactory test ; 8 vs 3 (p<0.002). There was a highly variable time to recovery from 9 days to >3 months. Large prospective studies are needed to track the course of olfactory dysfunction in COVID-19 patients.
Publication date / reference: 24/03/2021 Jeyanshree et al. Self-reported and clinically identified loss of smell and taste among persons tested for COVID-19 in Chennai, southern India, July-August 2020: A cross sectional study. Clin Epidemiol Glob Health
Summary: This cross-sectional study by Jeyashree et al. included 277 participants from sample collection centres in Chennai city, Southern India (219 negative and 58 positive for COVID-19). Overall 36 patients either reported loss of smell/taste and/or had these symptoms on clinical examination. Self-report was more common in patients negative for COVID-19 than identification of these symptoms by clinical examination, while patients positive COVID-19 were more likely to have loss of smell/taste identified by clinical examination. Patients who reported these symptoms were twice more likely to be positive for COVID-19 in comparison to COVID-19 negative participants (LRpos = 2·13).
Publication date / reference: 22/03/21 Cousyn et al. Olfactory and gustatory dysfunctions in COVID-19 outpatients: a prospective cohort study. Infect Dis Now
Summary: This is a prospective observational study which sought to evaluate the evolution of olfactory and gustatory function in outpatients with COVID-19 (n=98). Participants were followed up via weekly telephone interviews over a 60 day period using standardised questionnaires. At 30 days, 67.5% of participants had recovery of smell and taste and the median time of recovery was 20 days. Individuals were more likely to have a later or prolonged recovery if they had complete loss of smell and taste at disease onset and if they were over 40-years-old. This is promising data demonstrating that the majority of patients with mild COVID-19 recover their sense of smell and taste after a month of illness.
Publication date / reference: 9/3/21 Ferreira Sbrana et al. Olfactory dysfunction in frontline healthcare professionals during COVID-19 pandemic in Brazil. Front Physiol.
Summary: This cross-sectional study (n=1376) aimed to investigate the prevalence of olfactory dysfunction amongst healthcare professionals in Brazil. 39.3% (n=541) of the participants tested positive for SARS-CoV-2. A 17 question online survey with data collected between May 29th and July 8th 2020. Taste disturbance present in 74.1% of infected participants and olfactory dysfunction in 83.9% (n=454). Olfactory dysfunction was higher in professionals working in close contact with COVID-19 patients; 61.5% in ICU vs 22.3% of those working in outpatient clinics (OR 2.4; CI 1.1-5.4, P=0.03).
Publication date / reference: 14/10/2020 de Souza et al. Response to Letter to the Editor: Taste and Smell Dysfunction in COVID-19 Patients. Ann Otol Rhinol Laryngol.
Summary: Short letter describing two cases of covid-19 associated phantosmia, parageusia, and parosmia.
Publication date / reference: 12/02/2021. Cao et al. Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing. World J Otorhinolaryngol Head Neck Surg.
Summary: Cao and colleagues conducted a prospective study which investigated the prevalence of anosmia and dysgeusia amongst healthcare workers with a history of SARS-Cov-2 infection, using self-administered smell and taste tests. Among participants with a history of SARS-Cov-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Participants with recent SARS-Cov-2 infection had significantly lower olfactory scores compared to other participants. There was a time-dependent increase in olfaction scores following infection, which was not observed for gustation scores.
Publication date / reference: 01/03/2021. Prta-Etessam et al. COVID-19 anosmia and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry. Infection.
Summary: The authors aimed to investigate if olfactory and gustatory dysfunction (OGD) in COVID-19 are good prognosis symptoms, a sub-analysis study as part of an ongoing large multicenter cohort study (N=5868). The study population were exclusively inpatients. Authors reported that in this cohort of patients, prevalence of OGD was 8.5%, and higher prevalence was found in younger populations. The olfactory and gustatory dysfunction was significantly more frequent in Afro-Americans and Latino-American than Caucasian or Asian people (p < 0.0001). Patients reporting a loss of smell had five-fold reduction in risk of death (OR0.026 p>0.001). The authors postulated that one explanation for this finding may be that patients with immune dysfunction could have less OGD, due to lower immune reaction and less epithelial and olfactive cells degeneration. Keeping in mind the limitations of the study, the finding that OGD symptoms are related to prognosis of COVID-19 could have important clinical implications in the treatment of COVID-19 patients.
Publication date / reference: 3/3/2021 Weiss et al. Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection. PLoS One.
Summary: This prospective cohort study aimed to determine if tracking smell sensitivity and loss using an at-home assessment could identify COVID-19 in healthcare workers (HCW). The authors performed tracking (n=473) HCW across three months with a longitudinal, behavioral at-home assessment of olfaction with household items. SARS-CoV-2 was identified at 3.6%. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire. 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss. They concluded that self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.
Publication date / reference: 26/02/2021 Capelli et al. Anosmia in the first coronavirus disease 2019 outbreak in Europe: functional recovery after eight months. J Laryngol Otol.
Summary: This study was one of the few in the literature at the time of writing which analysed longer-term recovery of anosmia in covid-19. They evaluated 55 patients who developed anosmia at the same time as covid-19 symptoms eight months later via interview. They showed that 53% had self-reported total recovery, with a further 38% partial recovery (9% no recovery). Limitations include no confirmed covid-19 in some patients (due to lack of testing at the time) and the telephone interview style of data collection with the usual inherent biases.
Publication date / reference: 12/02/2021 Cao et al. Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing. World J Otorhinolaryngol Head Neck Surg.
Summary: A survey of 250 healthcare workers found that 73% of individuals with previous COVID-19 reported olfactory and/or gustatory dysfunction. Those with recent infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was also a time-dependent increase in smell but not taste scores in those with prior infection and chemosensory symptoms.
Publication date / reference: 23/0121 Al-Shaks et al. The Association of Smell and Taste Dysfunction with COVID19, And Their Functional Impacts. Indian J Otolaryngol Head Neck Surg.
Summary: The authors aimed to measure the prevalence of insomnia and dysgeusia in n=274 COVID-19 patients in Saudi Arabia and investigate their functional and psychological effects on patients. Using the short version of the Olfactory Disorders-Negative Statements (sQODNS) Questionnaire, they found a very high prevalence of loss of smell or taste (>64% for each).
Publication date / reference: 01/01/2021 Bagnasco et al. Quick Olfactory Sniffin’ Sticks Test (Q-Sticks) for the detection of smell disorders in COVID-19 patients. World Allergy Organ J.
Summary: The authors report that from a sample of patients (n = 37) with varying degrees of covid-19 illness, 22 had hyposmia or anosmia on Q-stick exam. This was more than the five who reported subjective smell loss.
Publication date / reference: 28/01/2021. Koul et al. Olfactory and Gustatory Alterations in Covid-19 Patients: A Tertiary Care Covid-19 Centre Inpatient Experience. Indian J Otolaryngol Head Neck Surg.
Summary: Cross sectional study of selected cohort of patients admitted with COVID-19 (N=300), subjectively tested for olfactory and gustatory alterations. 53% (N=159) reported alteration in taste or smell within 5 days after testing positive for COVID-19. A proportion of patients reported olfactory dysfunction (19.52%) or gustroy dysfunction (45%) prior to testing.
Publication date / reference: 09/01/2021. Le-Bon et al. Efficacy and safety of oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell. Eur Arch Otorhinolaryngol.
Summary: This pilot study investigated the efficacy and safety of corticosteroid and olfactory training in the treatment of persistent olfactory dysfunction as a result of COVID-19. Extensive psychophysical testing was used to identify 27 individuals with persistent dyssomnia at 5 weeks post infection. They then chose to receive either olfactory training alone or olfactory training with a 10 day course of oral corticosteroids. Olfactory function was then measured again after 10 weeks and showed patients in the OCS+OT group had significantly improved their olfactory score by 7.7 points on average compared to only 2.1 points in the olfactory training only group. It is worth noting however that participants were not randomised and only 9 participants agreed to be in the oral corticosteroid group. The authors advocate for larger cohorts and a control group of dysosmic patients would help separate the effect of treatment from spontaneous recovery
Publication date / reference: 03/01/2021 Yadav et al. Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Tertiary Care Institute Experience in India. Indian J Otolaryngol Head Neck Surg.
Summary: This single centre indian prospective observational study assessed inpatients PCR positive for SARS-COV-2 for olfactory and gustatory symptoms using self-report questionnaires on a weekly basis (baseline, 7 days, 14 days and discharge if after 14 days). Of 152 included patients, 28 had olfactory dysfunction and of these 13 had further dysguesia as well. In this group of 28 with olfactory dysfunction, 82% had resolution of their dysfunction by 7 days and all having resolved by 14 days. Dysguesia was noted in 20 patients and of these 55% had recovery of symptoms by 7 days and all by 14. Although a relatively small sample size the authors report this is the first indian single centre study to investigate olfactory/gustatory dysfunction in confirmed COVID-19 patients.
Publication date / reference: 16/01/2021 Lechien et al. Epidemiological, otolaryngological, olfactory and gustatory outcomes according to the severity of COVID-19: a study of 2579 patients. Eur Arch Otorhinolaryngol
Summary: A cross-sectional study of 2579 with a positive diagnosis of COVID-19 including 2166 mild (84.0%), 144 moderate (5.6%) and 269 severe-to-critical (10.4%) patients. Otolaryngological symptoms, including olfactory dysfunction (OD) and gustatory dysfunction (GD), were collected through a patient-reported outcome questionnaire. They concluded that OD and GD are more prevalent in patients with mild COVID-19 compared with individuals with moderate, severe or critical diseases. Females also had a higher prevalence of subjective OD and GD compared with males. Diabetes was associated with a higher risk to develop GD.
Publication date / reference: 14/01/2021. Rusetsky et al. Smell Status in Children Infected with SARS-CoV-2. Laryngoscope.
Summary: Cross-sectional survey of children (n = 79) with confirmed COVID-19. Smell impairment was detected in 86.1% of children by means of a Identification test and in 68.4% of children by means of a survey. The majority of (94.3%) had no subjective olfactory complaints by the end of the first month.
Publication date / reference: 12/01/21. Jain et al. Is there a correlation between viral load and olfactory & taste dysfunction in COVID-19 patients? Am J Otolaryngol.
Summary: The authors of this study assessed 200 COVID-19 patients, 100 of whom had olfactory and taste dysfunction and 100 of whom did not. The two groups did not differ significantly with regards to demographics but cycle threshold values of 3 genes assessed in COVID-19 RT-PCR: E (envelope encoding) gene, N (nucleocapsid encoding) gene, and RdRp (RNA-dependent RNA polymerase) gene differed significantly.
Publication date / reference: 6/1/2021. Niklassen et al. COVID-19: Recovery from Chemosensory Dysfunction. A Multicentre study on Smell and Taste. Laryngoscope.
Summary: This prospective cohort study assessed 111 patients who tested positive for SARS-CoV-2 at Day 3, 28 and 169. They undertook extensive olfactory testing and found a significant difference in olfactory function during infection compared to after the infection. During infection 21% were anosmic while after infection this was only 1%. For gustatory function there were significant changes in sour, bitter and and overall. They showed that a quarter of patients had persistent dysfunction and recommend referral to specialist clinics for rehabilitation.
Publication date / reference: 05/1/21. Nguyen et al. Long-term persistence of olfactory and gustatory disorders in COVID-19 patients. Clin Microbiol Infect.
Summary: The authors of this study randomly selected 200 patients who had previously reported anosmia and/or ageusia during a COVID-19 episode. Of the 125 who answered a questionnaire, 68.1% had recovered smell and 73.0% taste during the first six weeks following onset, with anosmia tending to take longer to resolve than ageusia. 30 patients reported persistent taste and smell disorders, and female patients were more likely to report persistent symptoms than male patients (p = 0.02).
Publication date / reference: 01/01/2021. Kavaz et al. Clinical significance of smell and taste dysfunction and other related factors in COVID-19. Eur Arch Otorhinolaryngol.
Summary: This retrospective survey study aimed to evaluate smell and taste dysfunction (STD) in COVID-19, and to assess the factors associated with STD in COVID-19 patients. The authors identified (n=210) patients who tested either (n=53) positive or (n=51) negative for SARS-CoV-2 by RT-PCR, and applied telephone-based assessment to both groups. They found that STD was eightfold more frequent in the Positive Group. ‘Ground-glass appearance’ on chest-computed tomography was more frequent and median lymphocyte count was significantly lower in COVID-19 positive patients with STD. VAS scores were significantly lower than the pre- and post-COVID scores and STD scores were significantly correlated with anxiety scores but not correlated with nasal breathing scores. They concluded that STD may be related to increased inflammatory response as well as damage of olfactory neuronal pathway or non-neuronal olfactory mucosa.
Publication date / reference: Jan 2021. Mubaraki et al. Prevalence of anosmia among COVID-19 patients in Taif City, Kingdom of Saudi Arabia. Saudi Med J.
Summary: This retrospective cohort study aimed to calculate the incidence of anosmia and hyposmia amongst COVID-19 patients (n=1022). A total of 32.7% reported anosmia and 20.3% reported hyposmia following COVID-19 infection, with significantly higher rates amongst females, and younger patients.
Publication date / reference: 04/01/21. Niesen et al. Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell. Eur J Nucl Med Mol Imaging.
Summary: Niesen et al conducted a prospective study to assess cerebral correlates of dysosmia in COVID-19 patients using hybrid PET-MR imaging. COVID-19 patients (n=12) were imaged after reporting dysosmia with scans from healthy patients used at controls. The olfactory tracts were blocked bilaterally in six patients, and olfactory bulb asymmetry was observed in three. No changes were seen in higher cortical regions in any patients (p<.001). The authors concluded from this small sample that COVID-19 related dysosmia was caused by changes to olfactory structures rather than SARS-CoV-2 neuroinvasion.
Publication date / reference: 22/10/20. Romero-Gameros et al. Evaluation of predictive value of olfactory dysfunction, as a screening tool for COVID-19. Laryngoscope Investig Otolaryngol.
Summary: Romero-Gameros and colleagues used a cross-sectional, observational design to investigate the utility of olfactory dysfunction as a clinical screening tool for COVID-19. Patients (n=139) completed a psychophysical olfactory test after which they were tested for SARS-Cov-2 using PCR. The authors report a PPV of 73.46% and NPV of 60% for this novel screening tool; concluding these do not justify its use as a screening tool in isolation.
Publication date / reference: 25/12/20. Gerkin et al. Recent smell loss is the best predictor of COVID019 among individuals with recent respiratory symptoms. Chem Senses.
Summary: This multinational study used a cross-sectional, case-control design to identify if smell loss/anosmia could be used to predict COVID-19 infection. The authors recruited participants who tested positive (n=4148) and negative (n=546) for COVID-19 and completed 10 point self-report questionnaires on loss of smell. Using logistic regression models, the authors found loss of smell during active infection was the best predictor of infection (ROC AUC=0.72). Gerkin and colleagues suggest the screening of anosmia when contact tracing individuals thought to have been in contact with a positive case where laboratory testing cannot be utilised.
Publication date / reference: 21/12/20. Mangia et al. Olfactory function and findings on chest computed tomography in COVID-19: is there any correlation? Acta Otolaryngol.
Summary: The authors of this cross-sectional study aimed to compare olfactory and chest CT findings in patients hospitalised with COVID-19 (n=57). Olfaction was quantitatively assessed using the Alcohol Sniff Test and CT scans were analysed by a blinded radiologist. The authors found no correlation between olfactory function and the extent of lung involvement or CT indicators of disease severity.
Publication date / reference: 19/01/2021 Mazzoli et al. Olfactory function and viral recovery in COVID-19. Brain Behav.
Summary: Mazzoli and colleagues conducted a prospective cohort study investigating the association between viral recovery (testing negative for SARS-CoV-2 infection) and objective assessment of olfactory function as evaluated using the Smell Identification subtest of the Sniffin’ Sticks Test (SI-SST). 51 patients with (previously) confirmed SARS-CoV-2 infection were included. At the point of enrollment, 45% were clinically recovered (afebrile, not requiring oxygen) and 39% had viral recovery. The authors found that subjective, self reported olfactory disorders were not associated with clinical or viral recovery. However, there was a significant correlation between viral recovery and SI-SST sores (OR = 2.242; 95% CI 1.322–3.802, p < .003). The authors conclude that objectively assessed olfactory function recovery is associated with viral recovery.
Publication date / reference: 13/01/2021. Kumar et al. Loss of smell and taste in COVID-19 infection in adolescents. Int J Pediatr Otorhinolaryngol.
Summary: This is a prospective cohort study examining the prevalence, clinical course and outcomes of olfactory and taste dysfunction in adolescents with COVID-19 (n=141). 28.4% (40/141) patients had olfactory or taste dysfunction. Of these, 19.8% (28/141) had both. 24.1% (34/141) had olfactory dysfunction. Of these, 16 had hyposmia and 18 had anosmia. Dysguesia was noted in 24.1% (34/141) patients. The mean duration of these symptoms was 5.7 days.
Publication date / reference: 12/021/2021 Salcan et al. Is taste and smell impairment irreversible in COVID-19 patients? Eur Arch Otorhinolaryngol
Summary: This prospective study included 94 COVID-19 patients. Smell and taste tests were applied to all patients. Ten days after the first test, a second test was applied to the patients with an impaired sense of smell to compare the results. Of the 94 patients, 55.3% were male, and the mean age was 53 ± 19.6 (21–90) years. There were 67 patients with smell and taste impairment, of whom 34 (50.7%) had smell impairment only, 3 (4.4%) had taste impairment only, and 30 (44.7%) had both smell and taste impairment. It was found that the smell scores of 55 patients with smell and taste impairment in the first evaluation were significantly higher at the second measurement; and their tasting period was significantly shortened compared to the first measurement (p˂0.001). From this study it can be concluded that impairments in smell and taste are common in COVID-19.
Publication date / reference: 01/01/2021. Burak Numan Ugurlu et al. Quantitative evaluation and progress of olfactory dysfunction in COVID-19. Eur Arch Otorhinolaryngol.
Summary: This study aimed to assess olfactory dysfunction in COVID-19 using the Brief Smell Identification Test (BSIT). 42 patients were surveyed, and the authors noted a high rate of mild-moderate symptoms with a high rate of recovery in the 3 month follow up. 40% of the patients had olfactory disturbance as the first symptom, thereby emphasizing the importance of inquiring about olfactory function for early diagnosis.
Publication date / reference: 24/11/2020 Lechien et al. Severity of Anosmia as an Early Symptom of COVID-19 Infection May Predict Lasting Loss of Smell. Front Med (Lausanne).
Summary: This prospective observational study aimed to evaluate the recovery rate of loss of smell (LOS) with objective olfactory testing in COVID-19 patients. The authors recruited n=88 adults with confirmed COVID-19. Patients were evaluated using self-reported sudden LOS, objective olfactory evaluation (Sniffin-Sticks-test) and repeated evaluation until scores returned to normal levels. They found LOS developed after general symptoms in 44.6% of cases and 25.0% recovered olfaction within 14 days following the onset of LOS. The smell function recovered between the 16th and the 70th day post-LOS in 54.5%. At 2 months, 20.5% of patients had not achieved normal levels of olfactory function. Higher baseline severity of olfactory loss was strongly predictive of persistent loss (p < 0.001). They conclude that 79.5% of patients may expect to have complete recovery of their olfactory function. The severity of olfactory loss may predict the lack of mid-term recovery.
Publication date / reference: 08/12/2020. Vaira et al. Efficacy of corticosteroid therapy in the treatment of long- lasting olfactory disorders in COVID-19 patients. Rhinology.
Summary: Vaira et al conducted a multicentre randomised case-control study evaluating the efficacy of corticosteroid therapy in the treatment of long-lasting olfactory disorders in COVID-19 patients. 18 patients with COVID-19 related anosmia/severe hyposmia lasting longer than 30 days were involved. 9 were randomised to receive systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days, while the other 9 were untreated. Olfactory function was evaluated with the CCCRC test at 20 and 40 days from the first evaluation. The authors found that there was a significantly higher improvement in olfactory function within the treatment group compared to the control group at both the 20 days and 40 days follow up, suggesting that this combination of treatment may be effective in reducing the long-term olfactory morbidity of COVID-19.
Publication Date/Reference: 25/11/2020. Bulğurcu et al. Assessment of Smell and Taste Disorders in COVID-19: A Cross-sectional Study. J Craniofac Surg.
Summary: This cross-sectional study aimed to evaluate the relationship between the severity of the disease and the loss of smell and taste. The authors divided patients diagnosed with COVID-19 (n=418) into 3 groups: home-quarantined, hospitalized, and intensive care patients. The disease, smell, and taste functions of patients were evaluated with visual analog scores before diagnosis of COVID-19, during the disease, and fourth week after recovery. They found changes in smell and taste loss during the disease in all 3 groups. The smell loss rates determined in groups 1 to 3 were 45%, 43.7%, and 31.2%, respectively. The taste loss rates determined in groups 1 to 3 were 46.6%, 32.1%, and 31.2% respectively. The rate of patients with a total recovery of smell loss in groups 1 to 3 were 95.5%, 93.7%, and 100%, respectively. The rate of patients with a total recovery of taste loss in groups 1 to 3 were 97.1%, 91.4%, and 100%, respectively. The authors concluded that COVID-19 causes loss of smell and taste in a large proportion of patients. In this sample the loss of smell and taste did not correlate with the severity of COVID-19 disease, and improved at a high rate after the disease.
Publication date / reference: 21/11/2020. Kajumba et al. COVID-19-Associated Guillain-Barre Syndrome: Atypical Para-infectious Profile, Symptom Overlap, and Increased Risk of Severe Neurological Complications. SN Compr Clin Med.
Summary: Kajumba et al present a review of Guillain-Barre syndrome (GBS) associated with COVID-19 infection. Analysis of 51 case reports showed althought CSF investigations revealed signs of neuroinflammation, SARS-COV-2 was not found in any of the samples. 4 patients had antiganglioside antibodies. 39.2% (20/51) patients required mechanical ventilation.
Publication date / reference: 25/11/2020 Gözen et al. Evaluation of Olfactory Function With Objective Tests in COVID-19-Positive Patients: A Cross-Sectional Study. Ear Nose Throat J.
Summary: In this study, patients admitted to hospital with COVID-19 (n=59) were screened with a questionnaire about smell dysfunction, and ten underwent the Snifffin’ Sticks test. The rate of olfactory dysfunction in COVID-19 patients was 53% via the questionnaire, but was 83% with the Sniffin’ Sticks.
Publication date / reference: 25/11/2020 Altundag et al., The temporal course of COVID-19 anosmia and relation to other clinical symptoms. Eur Arch Otorhinolaryngol
Summary: This single-centre retrospective study aimed to investigate the presence of anosmia in COVID-19 patients, clinical features and course in comparison to other symptoms. Patients were retrospectively identified (n=135), then contact was made for self-reported symptoms. Average duration of olfactory symptoms ranged from 21-40 days, and 59.3% of the patients had olfactory symptoms. The authors noted that risk factors included: female sex and lower age.
Publication date / reference: 11/11/20. Perera Samaranayake et al. Attributes of Dysgeusia and Anosmia of Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients. Oral Dis.
Summary: This study obtained information on chemosensory dysfunction and history of chronic systemic comorbidities from 149 COVID-19 patients in an infectious disease hospital in UAE. The authors utilised medical records, a face-to-face questionnaire and the SNOT-22 in order to assess chemosensory dysfunction in COVID-19. Dysfunction was reported by 94.6% of the cohort and anosmia with dysgeusia were significantly more in males than females with severe COVID-19. Males with moderate COVID-19 and systemic comorbidities were more likely to present with chemosensory dysfunction in comparison to females. The authors concluded that their data suggested that chemosensory dysfunction is common in COVID-19 and more pronounced in males with severe disease.
Publication date / reference: 11/11/2020 Ardestani et al. The coronavirus disease 2019: the prevalence, prognosis, and recovery from olfactory dysfunction (OD). Acta Otolaryngol
Summary: The multi-centre cross-sectional study (6) aimed to investigate the prevalence of OD in COVID-19 patients (n=311). There was acute OD in 164 (79.2%) of the sample, and there was gradual OD in 43 (20.8%). There were fluctuating OD symptoms in 39% of patients. 179 (86.4%) showed recovery from OD within a month. Their findings suggest that nasal obstruction, platelet count could help determine the severity of OD in patients with COVID.
Publication date / reference: 16/11/2020. Jain et al. Olfactory and taste dysfunction in coronavirus disease 2019 patients: its prevalence and outcomes. J Laryngol Otol.
Summary: This prospective cross-sectional study aimed to evaluate the occurrence, clinical course and outcomes of olfactory and gustatory dysfunction in patients with laboratory confirmed COVID-19. The authors included 410 patients with COVID-19 confirmed by reverse transcription polymerase chain reaction over two months and found that 63.9% were male, 24.1% reported chemosensory dysfunction, of which 20.7% reported both olfactory and taste dysfunction. The mean duration of olfactory and taste dysfunction was 4.9 days, with a range of 2-15 days, and more common in females.
Publication date / reference: 04/11/2020 Rocha-Filho and Magalhães. Headache associated with COVID-19: Frequency, characteristics and association with anosmia and ageusia. Cephalalgia.
Summary: This cross-sectional study aims to assess the frequency and characteristics of headache in patients with COVID-19. It also aims to determine whether there is an association between headache and anosmia or ageusia. The authors included patients admitted to hospital with COVID-19 (confirmed on RT-PCR) (n=73). They found that headaches associated with COVID-19 are frequent, generally severe, diffuse, present a migraine phenotype (p<0.05) and are associated with anosmia and ageusia (OR: 5.39; 95% CI:1.66–17.45; logistic regression). Patients with anosmia and ageusia presented headache associated with phonophobia more often compared to those with headache without these complaints (Chi-square test; p < 0.05).
Publication date / reference: 28/10/2020. Sanli et al. Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia. Am J Otolaryngol.
Summary: In this case-control study Sanli et al. investigated the relationship between levels of IL-6 and the presence of anosmia in 59 patients with COVID-19 (23 with anosmia; 36 without anosmia). Overall serum IL-6 levels in all patients with COVID-19 were above normal values (7 pg/mL), however patients without anosmia had significantly lower levels of IL-6 (16.72 ± 14.28 pg/mL) compared to patients without anosmia (60.95 ± 89.33 pg/mL) (p = 0.026). Based on these results and previous reports that higher IL-6 levels relate to a more rapid progression and higher complication rate of COVID-19, the authors hypothesised that anosmic cases might be less severe.
Publication date / reference: 24/10/2020. Schönegger et al. Smell and Taste Disorders in COVID-19 Patients: Objective Testing and Magnetic Resonance Imaging in Five Cases. SN Compr Clin Med
Summary: The authors investigated the neural correlates of altered smell and taste in five patients with COVID-19 at two timepoints. The chemosensory deficit was confirmed by objective clinical assessment. One patient’s initial scan demonstrated a slightly hyperintense signal in the caudate nucleus, parahippocampal gyrus, and the uncus of the left side. However, this was not found on the follow-up scan and was assumed to be within normal limits. This patient aside, there was no evidence of any neurological abnormalities on MRI in the five patients.
Publication date / reference: 07/11/2020 Tham et al. Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study Eur Arch Otorhinolaryngol
Summary: This retrospective cross-sectional study aimed the investigate the presence of olfactory taste disorder in confirmed COVID-19 patients from 1 centre (n=1065). Their findings were that 143 (12.6%) of patients had OTD; only 12 of these (1.1%) had isolated OTD. More specifically, 126 (11.8%) had an olfactory disorder, with 41 of this having taste disorder simultaneously. 49 (4.6%) of patients had a taste disorder. The results suggest that COVID-19 can present with OTD only or in combination with other related symptoms. Risk factors for this included: female sex, and several symptoms including blocked nose and no fever.
Publication date / reference: 19/10/2020 Kandemirli et al. Olfactory Bulb MRI and Paranasal Sinus CT Findings in Persistent COVID-19 Anosmia. Acad Radiol.
Summary: In this imaging study, 23 patients with persistent post-covid anosmia (1 – 4 months) undertook an MRI and CT. Olfactory cleft opacification was seen in 74%, 44% had below normal olfactory bulb volumes, 61% had shallow olfactory sulci, and in total 91% of cases had abnormality in olfactory bulb signal intensity. Their findings suggest that in persistent post-covid anosmia, there may be damage or atrophy of the olfactory bulb, which has implications for recovery. The authors judiciously pointed out that their evidence does not support the direct neurotropic hypothesis, and findings are best explained as collateral or bystander inflammatory damage. Of note, the above imaging findings are non-specific, and may be seen in patients with normosmia.
Publication date / reference: 26/10/2020 Seo et al. Trend of Olfactory and Gustatory Dysfunction in COVID-19 Patients in a Quarantine Facility. J Korean Med Sci.
Summary: This prospective surveillance study assessed olfactory and gustatory symptoms in 62 mildly affected individuals who were being isolated. 15/62 individuals reported olfactory or gustatory symptoms. There were no anatomical abnormalities in the nasal, on endoscopic evaluation, or oral cavity.
Publication date / reference: 24/10/20. Hatipoglu et al. Olfactory bulb magnetic resonance imaging in SARS-CoV-2-induced anosmia in pediatric cases. Int J Pediatr Otorhinolaryngol.
Summary: The authors report three cases of paediatric patients with COVID-19 infection who presented with different symptoms and also anosmia and/or ageusia.
Publication date / reference: 20/10/20 Niesen et al. Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell.
Summary: This prospective cohort study assessed twelve individuals (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) who had sudden onset dysosmia and were SARS-CoV-2 positive on nasopharyngeal testing. They performed MRI and FDG-PET simultaneously and found that sudden loss of smell is not centrally mediated via neuro-invasiveness but due to “heterogeneous cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganisation secondary to the lack of olfactory stimulation.
Publication date / reference:
Summary: The authors compared self reports of smell/taste change across several different countries (France, Italy, UK). The authors found that self reports of smell/taste changes are more closely associated with hospital overload, that a decrease in self report was seen as early as five days after lock-down, countries adopted the most stringent lockdown had faster declines in new reports of smell/taste changes. The findings led the authors to propose that it can be used as an earlier marker of the spread of infection than current government indicators. However the findings should be taken with caution due to the lack of control for confounding factors (e.g. media influence).
Publication date / reference: 13/10/20. Altundag et al. Olfactory Cleft Measurements and Covid-19- Related Anosmia. Otolargyngol Head Neck Surg.
Summary: This study compared the difference in olfactory cleft in patients of anosmia due to SARS-Cov-2 (n=24) to those with anomia to other viral infections (n=38) and control (n=29). The investigator found patients with COVID-19 anosmia had higher olfactory cleft width and volumes; and a higher T2 signal on MRI scan of the olfactory bulb, compared to control, suggesting underlying inflammatory changes.
Publication date / reference: 09/10/2020. Iannuzzi et al. Gaining back what is lost: recovering the sense of smell in mild to moderate patients after COVID-19. Chem Senses.
Summary: Cohort study which aimed to quantify recovery of anosmia/hyposmia in 30 mild-moderate cases of covid-19. Almost all subjects showed resolution of their symptoms at one month on the Sniffin’ Sticks Test.
Publication date / reference: 30/09/2020 Rajkumar et al. Contemporary Analysis of Olfactory Dysfunction in Mild to Moderate Covid 19 Patients in A Tertiary Health Care Centre. Indian J Otolaryngol Head Neck Surg.
Summary: This study aimed to assess the prevalence of olfactory dysfunction in COVID-19 patients by objective assessment in mild to moderate symptomatic patients. On quantitative assessment of smell dysfunction, 41% (n=95) patients had some form of smell dysfunction out of which 71% patients (n=67) had hyposmia and 30% patients (n=28) had anosmia.
Publication date / reference: 14/09/2020 Amer et al. Early recovery patterns of olfactory disorders in COVID-19 patients; a clinical cohort study. Am J Otolaryngol.
Summary: A cross-sectional cohort study of 96 patients with olfactory dysfunction secondary to COVID-19. At follow-up, 25% showed no recovery within one month.
Publication date / reference: 01/10/20. Talavera et al. Anosmia is associated with lower in-hospital mortality in COVID-19. J Neurol Sci.
Summary: The authors of this retrospective case-note review (n=576) report that COVID-19 patients with anosmia are less likely to be admitted to the ICU or die. Patients with anosmia were younger, with a higher percentage of women, less disability at baseline, and with fewer comorbidities. These patients also had higher lymphocytes, GFR, and lower d-dimer values than patients who did not report anosmia. The authors speculate that patients with anosmia may have a distinct clinical presentation and a different inflammatory response.
Publication date / reference: 28/09/20. Karimi-Galougahi et al. Emergence and Evolution of Olfactory and Gustatory Symptoms in Patients with COVID-19 in the Outpatient Setting.
Karimi-Galougahi and colleagues present findings from a prospective cross-sectional study evaluating the prevalence of general and sinonasal symptoms in patients with olfactory symptoms and mild COVID-19. A self-administered questionnaire was completed by 76 outpatients with new onset olfactory dysfunction at an otorhinolaryngology clinic. All participants had PCR confirmed COVID-19. Anosmia was present in 60.5% of patients and 39.5% had hyposmia. During the 2-week follow up period, 30.3% of patients completely and 44.7% partially recovered from their reported olfactory dysfunction.
Publication date / reference: 30/09/20. Vaira et al. Gustatory Dysfunction: A Highly Specific and Smell-Independent Symptom of COVID-19. Indian J Otolaryngol Head Neck Surg.
Vaira and colleagues conducted objective assessments of olfactory and gustatory function in 556 patients with confirmed SARS-Cov-2 infection. In the assessment, a 1 ml drop of 4 different solutions (salty, sweet, sour and bitter) were administered in turn onto the centre of the patients tongue, with deionised water being used as a control. The patients then reported a taste score of 0 to 4 with 4 indicating normal taste and 0 indicating ageusia. At the same time, patients underwent olfactory assessment with the Connecticut Chemosensory Clinical Research Center orthonasal olfaction test and a self-administered psychophysical olfactory test. Isolated gustatory dysfunction was reported in 9.4% of patients. 51.1% reported gustatory dysfunction alongside olfactory dysfunction. In patients with combined dysfunction, 17.9% reported their gustatory dysfunction was more severe than their olfactory dysfunction.
Publication date / reference: 10/09/20. Prajapati et al. Association of subjective olfactory dysfunction and 12-item odor identification testing in ambulatory COVID-19 patients. Int Forum Allergy Rhinol.
Summary: This prospective study captured subjects immediately post-COVID-19 diagnosis and concurrently obtained self-reported and psychophysical olfactory measurements. The authors hypothesised that patients with SARS-CoV-2 infection related smell loss can detect their loss with high sensitivity and that the two measurements may be more strongly correlated than previously reported for other pathologies. A total of 81 outpatients were recruited. At the time of initial recruitment, 27 reported no smell loss while 54 had smell loss. Between those without subjective smell loss and with subjective smell loss, there was no difference in age (mean 43.8 vs 38.3 years; p=0.15) or gender (55.6% vs 57.4% male; p=0.36). A history of allergies and depression was more prevalent in those who reported no smell loss compared to those who did. Correlational analyses revealed a moderate correlation between self-reported and measured olfactory loss as assessed by VAS and BSIT scores, respectively (r=0.59, p<0.001). The authors concluded that, in the context of COVID-19, self-reported smell loss is relatively well correlated with measured olfactory dysfunction.
Publication date / reference: 10/09/20. Weiss et al. Tracking Smell Loss to Identify Healthcare Workers with SARS-CoV-2 Infection. medRxiv (pre-print, not peer-reviewed)
Summary: In this prospective cohort study, Weiss and colleagues tracked 473 healthcare workers who regularly performed at-home assessment and a screening questionnaire of smell function to determine whether changes in smell could identify COVID-19. The participants were regularly tested for SARS-CoV-2 using PCR, and infection was identified in 17 (3.6%). Of these positive participants, just over half (9/17) reported smell loss, and were more likely to report altered smell than negative participants. The majority of participants reported smell loss prior to the regularly administered PCR tests (median of 2 days prior), which the authors use as evidence that altered smell was predictive of COVID-19 positivity. The feasibility of using routine at-home testing in healthcare workers needs to be considered.
Publication date / reference: 04/09/20. La Torre et al. Anosmia and Ageusia as Predictive Signs of COVID-19 in Healthcare Workers in Italy: A Prospective Case-Control Study. J Clin Med.
Summary: This case-control study aimed to investigate the diagnostic accuracy of symptoms and signs in healthcare workers with SARS-CoV-2 infection. Cases (n=30) consisted of symptomatic healthcare workers with a positive RT-PCR test, whereas controls (n=75) consisted of symptomatic healthcare workers with negative RT-PCR tests. 16 cases were male compared to 23 controls. Data was collected through structured interviews by trained physicians. Anosmia was present in 93.3% and ageusia in 92%. There were significant differences between cases and controls in rates of dyspnoea (p=0.036), headache (p=0.023) and anosmia and ageusia combined (p<0.001). Logistic regression showed that anosmia (OR=14.75, 95% CI: 4.27-50.87), ageusia (OR=9.18, 95% CI:2.80-30.15), and headache (OR=3.92, 95% CI:1.45-10.56) are significantly associated with SARS-CoV-2 positivity. The authors concluded that they had provided one of the first examples of the diagnostic accuracy of symptoms in healthcare workers with COVID-19. Limitations included the small sample sizes and the lack of chemosensitive evaluation in anosmia and ageusia.
Publication date / reference: 01/09/20. Neto et al. Chemosensory Dysfunction in COVID-19: Prevalences, Recovery Rates, and Clinical Associations on a Large Brazilian Sample. Otolaryngol Head Neck Surg.
Summary: Prospective study of chemosensory function in patients following SARS-CoV-2 infection (n=655). At a median time of >2 months post-onset, self-reported rates of total and partial olfaction recovery were 53.8% and 44.7%, with taste completely recovered in 68.3% and partially in 27.6%. 4.1% reported no return to chemosensory function at follow up.
Publication date / reference: 26/08/20. Lima et al. Smell dysfunction in COVID-19 patients: More than a yes-no question. J Neurol Sci.
Summary: The authors conducted a prospective case-control study to evaluate olfactory dysfunction in 57 confirmed COVID-19 patients, and 34 healthy controls, using a three-item smell identification test. They found a gradient of effect with higher (better) scores in healthy controls, followed by COVID-19 patients who did not report smell loss, then COVID-19 patients who did report smell loss. The authors concluded that olfactory dysfunction in COVID-19 is common, perhaps more prevalent than perceived by patients, and not a ‘binary’ yes/no condition.
Publication date / reference: 27/08/20. Strauss et al. Olfactory Bulb Signal Abnormality in Patients with COVID-19 Who Present with Neurological Symptoms. AJNR Am J Neuroradiol.
Summary: This retrospective case-control study aimed to compare the olfactory bulb and olfactory tract signal intensity on thin-section T2WI and postcontrast 3D T2 FLAIR images in patients with confirmed COVID-19 with neurological symptoms (n=12) and age-matched controls with anosmia (n=12). There was no significant age difference between the groups but there were significantly more women in the anosmia control group. There was no significant difference between groups in the grading of paranasal sinus mucosal disease. The authors reported a significant difference in olfactory bulb FLAIR signal between COVID-19 patients and controls, 1.85 vs 1.27 (p=0.003). Neither group displayed olfactory bulb volume loss or signal abnormality based on thin-section T2WI. The authors concluded that their preliminary findings indicated that olfactory vulnerability to COVID-19 might be supported on conventional neuroimaging. Of note, these results are in contrast to the emerging literature which points away from a CNS cause of anosmia, although the situation is likely to be more complex than a simple central vs peripheral dichotomy.
Publication date / reference: 27/08/20. Otte et al. Olfactory dysfunction in patients after recovering from COVID-19. Acta Otolaryngol.
Summary: In this prospective study, Otte and colleagues explored whether COVID-19 patients who had developed an olfactory and taste disorder during the course of their disease still reported reduced olfactory function at least three weeks after diagnosis (n=91, PCR-confirmed). The majority of patients (80/91) had experienced sudden olfactory loss at some point in their illness and 33 still had an impaired olfactory sense, eight weeks after the onset of COVID-19 symptoms. The authors assessed each patient with a validated olfactory test and found that 45.1% were still hyposmic while 53.8% had normal olfactory function. Interestingly, patients’ self-assessment correlated poorly with the measured olfactory performance and it is unclear why not all of the patients with an objective deficit noticed any change in their sense of smell.
Publication date / reference: 22/07/20. Farah Yusuf Mohamud et al. Loss of taste and smell are common clinical characteristics of patients with COVID-19 in Somalia: a retrospective double centre study. Infect Drug Resist.
Summary: The authors of this study retrospectively assessed clinical features of 60 patients with COVID-19 and found that 80% had at least ageusia or anosmia. Myalgia or fatigue was present in 53.3% of patients, whilst anosmia and ageusia were reported in 40% and 28.3% respectively. A combination of both taste and smell loss was seen in 11.7% of patients.
Publication date / reference: 06/08/20. Klopfenstein et al. New loss of smell and taste: Uncommon symptoms in COVID-19 patients on Nord Franche-Comte cluster, France. Int J Infect Dis.
Summary: This retrospective observational study examined the prevalence and features of anosmia in COVID-19 patients (n=70). Patients were separated into two groups, patients with anosmia and without anosmia, in order to compare their characteristics. Seven symptoms were presented in more than half of the patients: Fatigue (93% n=65), cough (80% n=55), fever (77% n=54), headache (73% n=51), myalgia (59% n=55), arthralgia (54% n=38) and anosmia (53% 37). 10% (n=7) also had tinnitus and 6% (n=4) reported hearing loss. The mean duration of anosmia was 7.4 days. In 31 cases (84%), COVID-19 patients had both anosmia and dysgeusia. Patients with anosmia reported a higher number of symptoms than those without anosmia but had a lower Charlson comorbidity index. Patients with anosmia were less often hospitalised (13/37 vs 20/33, p=0.033). The authors concluded that they had presented evidence of high rates of anosmia among their cohort and that the evolution of SARS-CoV-2 infection may seem more favourable in patients with anosmia.
Publication date / reference: 04/08/2020. Cazzola et al. Taste and smell disorders in COVID-19 patients: role of Interleukin-6. ACS Chem Neurosci.
Summary: This prospective observational study examined the relationship between changes in blood levels of Interleukin-6 and the course of anosmia/dysgeusia in COVID-19 patients. 67 COVID-19 patients with taste and/or smell disorders, who did not require intensive care admission and were admitted to a single-centre had their blood assayed for IL-6 both at admission and swab negativisation alongside a survey to evaluate the severity of their taste/smell disturbances. Significant correlations were found between decreases in IL-6 and improvement in taste and smell in these patients. The authors argue that this may indicate the key role of IL-6 in the pathogenesis of chemosensitive disorders in COVID-19 patients although further research is required to elucidate the causality and mechanism by which IL-6 may mediate these disorders.
Publication date / reference: 07/08/20. Cocco et al. Neurological features in SARS-CoV-2-infected patients with smell and taste disorder. J Neurol.
Summary: Correspondence seeking to determine the prevalence of neurological symptoms in association with anosmia or dysgeusia. The authors described a retrospective cohort of 105 PCR-confirmed SARS-CoV-2-infected patients, 74% of whom had new-onset anosmia or dysgeusia. Symptoms with higher prevalence in these patients included headache, balance impairment, dysphonia, dizziness, mild confusion, sensory disturbances, and visual disturbances. In this study, anosmia and dysgeusia were unrelated to clinical severity.
Publication date / reference: 06/08/2020. Vaira et al. Do olfactory and gustatory psychophysical scores have prognostic value in COVID-19 patients? A prospective study of 106 patients. J Otolaryngol Head Neck Surg.
Summary: In this prospective study, patients (n = 106) were recruited at COVID-19 diagnosis and their olfactory and gustatory functions were measured. In total, 67% of patients had olfactory & gustatory disturbance. The authors aimed to use the presence or absence of olfactory/gustatory disturbance as a potential predictor of prognosis; this was despite a relatively short follow-up time of 20 days. In conclusion, higher olfactory and gustatory dysfunction was not associated with any prognostic value in this study.
Publication date/ reference: 01/08/20. Fjaeldstad. Prolonged complaints of chemosensory loss after COVID-19. Dan Med J.
Summary: In this cross-sectional study Fjaeldstad aimed to investigate the time course of recovery from olfactory and gustatory loss in patients with confirmed and suspected COVID-19. A questionnaire was used to collect information including symptoms of olfactory, gustatory and trigeminal sensory loss and symptoms of COVID-19. Participants who reported subjective olfactory dysfunction for more than two weeks were included (n=109). 95 participants reported olfactory and gustatory loss, five had isolated olfactory loss, and nine had isolated gustatory loss. After a mean of >30 days after chemosensory loss, 28% of participants had not yet experienced any improvement in their olfactory function, whereas 44% had fully recovered from their olfactory loss. After gustatory loss, 50% had fully recovered and 20% had not yet experienced any improvement. Limitations of this study include that COVID-19 wasn’t PCR confirmed in all participants, and the risk of recall and selection bias.
Publication date/ reference: 04/08/20. Leb Bon et al. Psychophysical evaluation of chemosensory functions 5 weeks after olfactory loss due to COVID-19: a prospective cohort study on 72 patients. Eur Arch Otorhinolaryngol
Summary: This study used a prospective design to follow up 72 patients who suddenly lost chemosensation with a confirmed COVID-19 infection. Follow-up was a mean of 37 days after symptom onset. Odor threshold detection was more affected than odor identification, which the authors suggest may indicate that the cause of loss of smell lies at the level of the olfactory neuroepithelium, rather than in the central nervous system. The authors found the majority of patients to have normal taste at follow-up, however. This study also found that almost half of the patients appeared to exhibit signs of abnormal nasal cooling sensation, prompting a call for more systematic investigations of trigeminal sensitivity in COVID-19.
Summary: This study used a survey design in order to attempt to verify the association of olfactory impairment and COVID-19. A 15-item questionnaire was administered to Italian GPs registered to a social media group. Respondents were asked about patients who had sudden onset olfactory disturbances during the COVID-19 outbreak in March 2020. 180 patients were described by 100 GPs. Among these, sudden olfactory loss was said to have occurred in 57.8% of females and 42.2% of males. 63.9% of recruited patients had contact with suspected cases and 46.7% had contact with confirmed COVID-19 cases. In terms of severity of olfactory dysfunction, 65.6% of patients complained of severe loss, 27.2% were moderate and 7.2% had slight anosmia. The authors did not report on how these categories were ascertained. 26 patients had positive SARS-CoV-2 tests. The study concludes by suggesting that sudden olfactory disturbances without obstructive nasal conditions should be considered as potential COVID-19 cases.
Publication date / reference: 31/07/20. Lechien et al. Objective Olfactory Findings in Hospitalized Severe COVID-19 Patients. Pathogens.
Summary: This study aimed to investigate the prevalence of self-reported and objective sudden loss of smell in patients with severe PCR-confirmed SARS-CoV-2 infection. Severe disease was defined as requiring continuous care (oxygen therapy, blood pressure monitoring) in internal medicine or intensive care units. Patients with neurological disorders, chronic rhinosinusitis or a history of nasal surgery prior to the pandemic were excluded. Patient-outcome questionnaires were used to ascertain data on olfactory and gustatory disturbances. ‘Sniffin’stick’ tests were also used for an objective outcome. 47 severe COVID-19 patients completed evaluation. Objectively, four patients reported anosmia and nine reported hyposmia. From the subjective survey, eight and ten patients experienced anosmia and hyposmia. Limitations included the low number of patients, the lack of a control group and the performance of olfactory tests one month after onset of symptoms. The authors concluded that the prevalence of anosmia in severe COVID-19 patients appeared lower than other previous estimates.
Publication date / reference: 03/08/2020. Estomba et al. Patterns of Gustatory Recovery in Patients Affected by the COVID-19 Outbreak. Virol Sin.
Summary: In this prospective cohort study the authors collected data from patients reporting gustatory dysfunction in four University hospitals using a series of validated questionnaires (n=701). Patients were then grouped according to presence or absence of olfactory dysfunction. 92.6% of patients reported both forms of dysfunction. After a mean follow up of nine weeks about one in ten of patients reported persistent subjective gustatory dysfunction. In patients who had recovered, the mean duration of GD was 11 days. Limitations of this study include the lack of objective testing, loss to follow up and recruitment from ENT clinics, potentially introducing selection bias.
Publication date / reference: 09/07/20. Paolo. Does COVID-19 cause permanent damage to olfactory and gustatory function? Med Hypotheses
Summary: This retrospective study aimed to investigate the nature of smell and taste dysfunction in patients with COVID-19 (n=75), using an olfactory dysfunction questionnaire. All patients reported dysgeusia and the severity of olfactory dysfunction varied (e.g., 24/75 reported complete anosmia). The reported recovery time for all deficits was on average 17 days. The accuracy of this figure may have been affected by retrospective self-report introducing potential for recall bias. Paolo stated that a further aim of this study was to determine whether COVID-19 patients had the capability to recover their sensory deficits in comparison to patients with other rhinoviruses and inflammatory diseases. However, the retrospective design and absence of a control group does not allow for this question to be directly answered.
Publication date / reference: 20/07/20. Martin-Sanz et al. Prospective study in 355 patients with suspected COVID-19 infection. Value of cough, subjective hyposmia, and hypogeusia. Laryngoscope.
Summary: This case-control study analysed the incidence of COVID-19 symptoms in healthcare workers (n-335). Participants (n=335) with positive (n=215) and negative (n=140) RT-PCR results were included. A total of 138 positive cases (64.1%) and 114 positive cases (53.0%) had subjective hyposmia and hypogeusia respectively, which the majority (85.4%) recovered. The presence of hyposmia and hypogeusia was strongly associated with a positive RT-PCR (OR 4.88 and 3.51 respectively), which demonstrates the clinical value of these symptoms as indicators of COVID-19. The findings of this study are limited by the possibility of false RT-PCR results, whereby the negative RT-PCR group cannot be conclusively assessed as a ‘control’ or comparator group.
Publication date / reference: 10/07/20. Kirschenbaum et al. Inflammatory olfactory neuropathy in two patients with COVID-19. Lancet.
Summary: In this correspondence, the authors describe two male COVID-19 cases diagnosed with olfactory neuropathy at autopsy. They suggest possible routes of viral neuroinvasion and discuss in relation to anosmia.
Publication date / reference: 14/07/20. D’Ascanio et al. Olfactory Dysfunction in COVID-19 Patients: Prevalence and Prognosis for Recovering Sense of Smell. Otolaryngol Head Neck Surg.
Summary: Single-centre prospective case control study of PCR-confirmed COVID-19 patients (n=43; 23 outpatients, and 20 hospitalised but not requiring ICU) and 25 healthy controls. The authors examined the presence, severity, and duration of subjective olfactory dysfunction, four times longitudinally over one month. They found that COVID-19 positive outpatients were more likely to report disordered smell than inpatients, and both groups more likely than controls. In both disease groups the clinical course of olfactory dysfunction was favourable.
Publication date / reference: 14/07/20. Vargas-Gandica et al. Ageusia and anosmia, a common sign of COVID-19? A case series from four countries. J Neurovirol.
Summary: This is a case series of ten patients with RT-PCR-confirmed COVID-19 and olfactory or taste disturbance, from four different countries. The deficits occurred at early stages in this disease. Concordant with other reports of ageusia in COVID-19, there was concurrent disturbance of olfaction and the authors argued that the diminished taste perception was a consequence of anosmia.
Publication date / reference: 16/07/20. Chiesa-Estomba et al. Patterns of smell recovery in 751 patients affected by the COVID-19 outbreak. Eur J Neurol.
Summary: This large prospective study evaluated anosmia symptoms using an online questionnaire of 751 patients with confirmed COVID-19 (by RT-PCR or a positive IgG/IgM). There were 621 patients (83%) who subjectively reported a complete loss of smell and 130 (17%) a partial loss. After a mean follow-up of 47±7 days, 107 (14%) reported partial recovery and 367 (49%) reported complete recovery. At follow-up, 277 (37%) of patients still reported a persistent subjective loss of smell. These subjective patterns of recovery bear helpful insights into the trajectory of anosmia in COVID-19 but are limited by the exclusion of patients with severe disease, loss to follow-up and lack of objective anosmia testing.
Summary: The authors aimed to investigate clinical and radiological features of olfactory clefts of patients with mild PCR-confirmed COVID-19 (n=16). Nasal complaints were assessed through the unusually-named sino-nasal outcome test 22 (SNOT-22). Patients underwent psychophysical olfactory testing, olfactory cleft examination and CT scan. All patients were anosmic, but only three had complete opacification of the olfactory clefts. The authors concluded that while obstruction of the olfactory cleft may play a small role in increasing the severity of the olfactory dysfunction, it does not appear to be the primary underlying mechanism.
Publication date / reference: 08/07/20. Reiter et al. Subjective smell and taste changes during the COVID-19 pandemic: short term recovery. Am J Otolaryngol
Summary: This prospective cohort study used a web-based survey to assess the subjective decrease in smell and taste, over one-month. Of the 549 participants, 260 (47.4%) were COVID-19-confirmed by testing or diagnosed by a medical professional. It is unclear how the diagnosis was made and whether this was corroborated using medical notes. For the unconfirmed participants (52.6%), it is unclear how a probable diagnosis of COVID-19 was made. At 1-month follow-up, 67.1% reported a return to “very good” or “good” smell, and 73.1% reported a return to “very good” or “good” taste. The follow-up was completed by 36.8% of the cohort, but the results are not presented separately for individuals with a confirmed COVID-19 diagnosis.
Publication date / reference: 01/07/20. Hintschich et al. Psychophysical tests reveal impaired olfaction but preserved gustation in COVID-19 patients. Int Forum Allergy Rhinol.
Summary: This controlled, prospective study evaluated olfaction and gustation in n=41 patients with a positive SARS-CoV-2 test, and n=30 controls who had tested negative for the virus. The authors found that COVID-19 was associated with olfactory loss but not with gustatory dysfunction. They suggest that the subjective loss of taste is due to impaired retronasal olfaction, rather than a primary disorder of gustation.
Publication date / reference: 01/07/20 Petrocelli et al. Remote psychophysical evaluation of olfactory and gustatory functions in early-stage coronavirus disease 2019 patients: the Bologna experience of 300 cases. J Larygngol Otol.
Summary: Here the authors use a newly validated self-administered chemosensitive test that can be performed remotely, using common household items, to objectively evaluate olfactory and gustatory functions. N=300 confirmed COVID-19 patients were coached by phone to test themselves at home within the first seven days of symptoms onset. 70% of patients had a chemosensitive disorder, breaking down into 54.7% with both taste and smell affected, 8.7% isolated olfactory disorders, and 6.7 % isolated taste disorder.
Publication date / reference: 20/06/20 Parma et al. More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. Chem Senses.
Summary: This cross-sectional, international survey of n=4039 laboratory- or clinically-confirmed COVID-19 patients studied the frequency and co-occurrence of abnormal smell, taste, and chemesthesis (detection of sensations in the mouth like burning, cooling or tingling). The authors conclude that common COVID-19-associated chemosensory impairments extend beyond smell to affect taste and chemesthesis, perhaps independently of nasal obstruction. Distorted smells and phantom smells were less common but still clinically significant (7-9%).
Publication date / reference: 18/06/20 Freni et al. Symptomatology in Head and Neck District in Coronavirus Disease (COVID-19): A Possible Neuroinvasive Action of SARS-CoV-2. Am J Otolaryngol
Summary: This observational cohort study examined ear, nose and throat symptoms (smell, taste, hearing, salivation, tearing) in patients with laboratory-confirmed Covid-19 infection using validated measures. During active infection, the presence of olfactory dysfunction was reported in 92% of cases (anosmia=42%; hyposmia=50%). Olfactory symptoms preceded onset of other Covid-19 symptoms in 40% of cases and persisted during recovery in 18%. Gustatory disorders were reported by 70% of the sample during active infection, all of whom also reported olfactory dysfunction. Eye dryness (72%), xerostomia (32%), and auditory symptoms (hearing loss=40%; tinnitus=20%) were present in a notable proportion of cases. The authors argue that these findings support the proposed neurotropism of SARS-CoV-2 and the presence of early anosmia, dysgeusia and xerostomia may indicate quarantine to reduce viral transmission.
Publication date / reference: 16/06/20 Rodriguez et al. Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients. MedRxiv (preprint).
Summary: Through work in mouse models and observational studies on patients with SARS-CoV-2, the authors propose inflammatory-mediated loss of odorant receptor expression with preserved circuit integrity accounts for the olfactory dysfunction in COVID-19.
Publication date / reference: 16/06/20 Biadsee et al. Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis. Otolaryngol Head Neck Surg.
Summary: This survey of n=140 PCR-positive and “mild” SARS-CoV-2 patients quarantined in a ‘Coronavirus hotel’ reported initial dysfunction of smell in 38% and taste in 32%.
Publication date / reference: 16/06/20 Qiu et al. Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study. Otolaryngol Head Neck Surg.
Summary: This multi-centre retrospective chart review reports the screening of n=394 COVID-19 patients for sudden olfactory and/or gustatory dysfunction, and the clinical course of the subset n=161 who endorsed it. About half of such patients were classified as having “mild” COVID-19. Of n=102 patients followed up three weeks later, 57% reported no improvement in taste and/or smell.
Publication date / reference: 09/06/2020 Da Costa et al. Olfactory and taste disorders in COVID-19: a systematic review. Braz J Otorhinolaryngol.
Summary: Systematic review of articles published up to April 25, 2020. 6 articles from the 1788 recorded met the inclusion criteria. 1475 patients of different ethnicities were assessed. 60.7% were found to have smell disorders and 56.4% taste disorders. Women were more affected than men. Olfactory/gustatory symptoms may occur in the absence of nasal obstruction/rhinorrhea, and before other signs/symptoms of COVID-19. Recovery usually happens in the first two weeks after COVID-19 resolution.
Publication date / reference: 29/05/20 Letterio et al. Images in Neurology: Brain of Patient With COVID-19, Smell Loss. JAMA Neurology.
Summary: 25-year-old female radiographer who developed severe anosmia following work on a COVID-19 ward. Signal alterations on MRI (posterior gyrus rectus) suggest to the first known in vivo report of viral brain invasion in a cortical region that is associated with olfaction.
Publication date / reference: 25/05/20 Tsivgoulis et al. Quantitative evaluation of olfactory dysfunction in hospitalized patients with Coronavirus  (COVID-19). J Neurol.
Summary: Patients with SARS-CoV-2 (n=22) and aged-matched controls (n=22) compared using a three-scent strategy to compare olfaction. Only 23% of cases achieved normosmia compared with 64% controls.
Summary: Case (n=45) control (n=45, untested) study of olfaction in hospitalised patients with confirmed SARS-C0V-2. Using ‘Sniffin’ Sticks’ no controls demonstrated anosmia, whereas 40% of those diagnosed with SARS-CoV-2 displayed anosmia. Interestingly, 44% of those who were clinically anosmic reported having no problems with olfaction.
Publication date / reference: 19/05/20 Speth et al. Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics. Otolaryngology.
Summary: cross-sectional prospective study (n=102) analysing the rate and severity of olfactory disturbance in hospitalised SARS-CoV-2 patients. The prevalence of OD was 61%, with dysfunction often presenting early in the disease and very acutely.
Publication date / reference: 11/05/20 Pallanti et al. Importance of SARs-Cov-2 anosmia: From phenomenology to neurobiology. Comprehensive Psychiatry.
Summary: Case report of two patients who experienced anosmia and hypoguesia before the onset of respiratory symptoms and diagnosis of SARS-CoV-2. The authors set to remind us that these disturbances go beyond sensorineural disturbance – having implications in phenomenology.
Publication date / reference: 22/04/20 Beltrán-Corbellini et al. Acute-onset smell and taste disorders in the context of Covid-19: a pilot multicenter PCR-based case-control study. Eur J Neurol.
Summary: 79 cases and 40 controls (with influenza) demonstrate a significant difference in rates of anosmia and ageusia between groups. Limitations include historical control sample and self-report questionnaires. Concludes smell and taste disorders are often a first presentation of SARS-CoV-19 infection often occurring acutely.
Publication date / reference: 13/04/20 Galougahi et al. Olfactory Bulb Magnetic Resonance Imaging in SARS-CoV-2-Induced Anosmia: The First Report. Academic Radiology.
Summary: authors report the first known analysis of MRI in acute onset of anosmia. They claim there are no abnormalties, in keeping with MRI findings in SARS-CoV. “Eliezer et al. comment in a response to this article that there appears to be bilateral obstruction of the olfactory clefts and a report from Eliezer and co-authors on the subject is in press”.
Publication date / reference: 12/04/20 Yan et al. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol.
Summary: Internet-based cross-sectional analysis of the prevalence of smell and taste disturbance in confirmed COVID-19 patients vs a confirmed influenza subgroup. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of Covid-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of Covid-19-negative patients (p<0.001).
Publication date / reference: 06/04/20 Lechien et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID- 19): a multicenter European study. Eur Arch Otorhinolaryngol.
Summary: 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. Authors argue acute onset disturbance should prompt clinicians to include COVID-19 infection in their formulation.
Publication date / reference: 15/04/20 Bénézit et al. Utility of hyposmia and hypogeusia for the diagnosis of COVID-19. Lancet Infect Dis.
Summary: Authors report 63/68 and 51/68 cases of hypogeusia and hyposmia in patients testing positive for SARS-CoV-2. They explain potential causative mechanisms and argue for the clinical validity of using these clinical markers in patients with no ENT history.
Publication date / reference: 06/05/20 Lee et al. Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients. J Korean Med Sci.
Summary: Large scale cross-sectional study (telephone interview of 3,191) of prevalence of hyposmia and ageusia in mild-moderate severity cases of SARS-CoV-2 infection. Acute anosmia or ageusia was observed in 15.3% (488/3,191) patients in the early stage of COVID-19 and in 15.7% (367/2,342) patients with asymptomatic-to-mild disease severity.
Publication date / reference: 01/03/2021 Rezaeitalab et al. Detection of SARS-coronavirus-2 in the central nervous system of patients with severe acute respiratory syndrome and seizures. J Neurovirol.
Summary: This case series of four COVID-19 patients who had experienced loss of consciousness and seizure describes presence of SARS-CoV-2 in cerebrospinal fluid of all four patients, which the authors suggest is indicative of the virus’ potential to spread from the respiratory tract to the central nervous system.
Publication date / reference: 04/02/2021 Waters et al. Incidence of Electrographic Seizures in Patients With COVID-19. Front Neurol.
Summary: This four-centre retrospective case series evaluated the incidence of electrographic seizures in COVID-19 in 79 patients who had been connected to videotelemetry (cvEEG). The main indications for EEG monitoring were acute hyperkinetic movements, altered mental status, and persistent coma The authors found that 6/79 patients had cvEEG-proven seizures; half of these were new-onset. In those that had seizures the authors noted increased likelihood when focal slowing or when epileptiform changes were seen. They also noted that of these six patients, four were discharged and 2 (33.3%) died.
Publication date / reference: 16/02/2021 Asadi-Pooya et al. COVID-19 presentations and outcome in patients with epilepsy. Acta Neurol Scand.
Summary: The authors of this retrospective cohort study report on 37,968 patients with COVID-19 in Iran, 82 of whom had pre-existing epilepsy. Seizures were significantly more common as a presenting symptom of COVID-19 in people with epilepsy, and they were less likely to report cough but were more likely to have gastrointestinal symptoms. Case fatality rates did not differ.
Publication date / reference: 17/10/20. Karambelkar et al. The neurological manifestations of COVID-19–A case series. J Clin Transl Res.
Summary: The authors of this case series (n=2) describe two patients with COVID-19 who presented with seizure, in the absence of a history of epilepsy. The first patient (32-year-old gentleman) had respiratory symptoms in keeping with COVID-19 and subsequently developed acute respiratory failure – at this point the patient had a tonic-clonic seizure. The second patient (82-year-old gentleman) also deteriorated into respiratory failure but had a generalised tonic-clonic seizure after being mechanically ventilated.
Publication date / reference: 26/11/2020. Hautala et al. Respiratory viruses and febrile response in children with febrile seizures: A cohort study and embedded case-control study. Seizure.
Summary: This is a cohort study and embedded case-control study which compared the role of respiratory viruses and febrile response in children with febrile seizures. N=225 paediatric emergency room patients (aged 6 months to 6 years) with febrile seizures were evaluated. The embedded case control study assessed the febrile response in children with febrile seizures compared to age, season, and virus matched controls. The authors noted a higher risk of febrile seizures in influenza and coronavirus compared to other respiratory viruses. Additionally, a stronger febrile response was identified in patients with febrile seizures compared to the matched controls. This paper describes the pathogen and host related factors in the pathogenesis of febrile seizures.
Publication Date/Reference: 2/10/20. Minxian Sun et al. Clinical characteristics of 30 COVID-19 patients with epilepsy: a retrospective study in Wuhan. Int J Infect Dis.
Summary: This retrospective observational study by Sun et al. describes 30 hospitalised cases with epileptic seizure and COVID-19. The authors concluded that COVID-19 Patients with recurrent epileptic seizure had more underlying neurological diseases than patients who had epilepsy history but without seizure. Additionally, patients with new onset seizures experienced more severe COVID-19 with worse outcomes.
Publication date / reference: 19/09/20. Emami et al. Seizure in patients with COVID-19. Neurol Sci.
Summary: The authors aimed to study the occurrence of seizures in patients with COVID-19, and clarify the circumstances of the occurrence of seizures in people who are infected with this virus. They studied all consecutive patients attending healthcare facilities anywhere in Fars province, Iran (population 4.8 million) from February 19th until June 2nd with PCR- confirmed COVID-19. From a study sample of 6147, five patients had GTCS (0.08%).
Publication date / reference: 10/09/20. Gaughan et al. Acute new-onset symptomatic seizures in the context of mild COVID-19 infection. J Neurol.
Summary: The authors presented two cases with new-onset seizures in the background of mild COVID-19 respiratory symptoms. The first was an 87-year-old man who presented with a generalised tonic-clonic seizure. A previous history of traumatic brain injury was noted and all neuroimaging findings were thought to pertain to this insult. However, the second patient, a 77-year-old woman, had no prior neurological injury and developed a form of COVID-19 related encephalopathy and a severe and prolonged cognitive deficit. Persistent EEG abnormalities were also noted in this patient.
Publication date / reference: 02/06/20 Elgamasy et al. First Case of Focal Epilepsy Associated With SARS-Coronavirus-2. J Med Virol.
Summary: Case report of a 72-year-old patient with no history of epilepsy who developed persistent episodes of painful muscle stiffening and twitching in the left arm. She was found to have no abnormalities on neuroimaging but tested positive for SARS-CoV-2.
Publication date / reference: 26/05/20 Logmin et al. Non-epileptic Seizures in Autonomic Dysfunction as the Initial Symptom of COVID-19. J Neurol.
Summary: Case report of a patient admitted with recurrent non-epileptic seizures/convulsive syncope. The seizures were felt likely due to autonomic instability after all neurological investigations were negative.
Publication date / reference: 21/05/20 Rábano-Suárez et al. Generalized myoclonus in COVID-19. Neurology.
Summary: Case series (n=3) of patients who developed mild hypersomnia and generalised myoclonus during the course of their SARS-CoV-2 infection. No metabolic, biochemical or neuroimaging abnormalities were detected.
Publication date / reference: 16/05/20 Fasano et al. First Motor Seizure as Presenting Symptom of SARS-CoV-2 Infection. Neurological Sciences.
Summary: Case report of 54-year-old patient who presented with loss of consciousness and clonic movements in right arm. qRT-PCR confirmed SARS-CoV-2. Normal CT head and EEG.
Publication date / reference: 14/05/20 Somani et al. De Novo Status Epilepticus in patients with COVID-19. Annals Clin Translat Neurol.
Summary: Single centre retrospective case study (n=2) of patients with de novo status epilepticus with lab confirmed SARS-CoV-2 infection. In one patient, status was the presenting complaint.
Publication date / reference: 13/05/20 Balloy et al Non-lesional status epilepticus in a patient with coronavirus disease 2019. Clinical Neurophysiology.
Summary: Case report of a 59-year-old man who presented with fever, dry cough, dyspnea and headache. He exhibited short episodes of impaired consciousness together with confusion and behavioural disturbances. EEG showed widespread long rhythmic delta discharges with superimposed spikes in predominantly frontal localization simultaneous with impaired awareness. He was diagnosed with non-convulsive status epilepticus. CSF analysis was unremarkable and CSF SARS-CoV2 RT-PCR was negative.
Publication date / reference: 07/05/20 Garazzino et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Eurosurveillance.
Summary: Preliminary results of an Italian multicentre paediatric study (n=168), in five cases the children’s clinical picture included seizures. Three children had a history of epilepsy, whilst the remaining two were categorised as febrile.
Publication date / reference: 06/05/20 Galanopoulou et al. EEG findings in acutely ill patients investigated for SARS‐CoV2/COVID‐19: a small case series preliminary report. Epilepsia Open.
Summary: First preliminary report of EEG in acutely unwell COVID19 patients (n=22). Demonstrates presence of epileptiform discharges in 40% of positive patients.
Publication date / reference 01/05/2020 Sohal S et al. COVID-19 Presenting with Seizures. ID Cases.
Summary: Single case report of male with no previous history of seizures admitted to ICU after respiratory failure developing multiple seizures. RT-PCR for SARS COV-2 was positive. CT brain showed no acute changes; CSF findings not reported.
Publication date / reference: 18/04/2020 Lu L et al. New-onset acute symptomatic seizure and risk factors in Corona Virus Disease 2019: A Retrospective Multicenter Study. Epilepsia.
Summary: Retrospective case series (n=304) of COVID-19 positive patients: no seizures observed.
Publication date / reference: 21/04/2020 Vollono C et al. Focal status epilepticus as unique clinical feature of COVID-19 case report. Seizure.
Summary: Single case report of 78-year-old with focal status epilepticus. Past history (2 years ago) of HSV-1 encephalitis.
Publication date / reference: 28/03/2020 Karimi, N et al. Frequent Convulsive Seizures in an Adult Patient with COVID-19: A Case Report. Iran Red Crescent Med
Summary: Single case report of a COVID-19 positive 30-year-old female (previously healthy) admitted with tonic-clonic seizures; 5 seizures in 8-hour period. CT and MRI head were negative.
Publication date / reference: 15/05/20 Bianchetti et al. Clinical Presentation of COVID19 in Dementia Patients. Journal of Nutrition, Health and Ageing
Summary: Report on the clinical outcomes of 602 patients with confirmed SARS-CoV-2 in an acute Italian setting. Dementia was found to be an independent significant risk factor (logistic regression: age & sex) for mortality from the disease. The authors also describe delirium and worsening functional status as important first symptoms of the virus in this at-risk population.
Publication date / reference: 13/05/20 Liguori et al. Subjective Neurological Symptoms Frequently Occur in Patients With SARS-CoV2 Infection. Brain, Behaviour and Immunity.
Summary: Observational study of subjective neurological symptoms in inpatients (n=103) with confirmed SARS-CoV-2 infection. 91% of participants reported at least one of a 13-point checklist. Sleep was most commonly disturbed, while patients also report high rates of subjective dysgeusia, headache, hyposmia, and depression.
Publication date / reference: 05/05/20 Benussi et al. Clinical characteristics and outcomes of inpatients with neurological disease and COVID-19. MedrXiv (preprint).
Summary: Retrospective cohort study of 173 patients, of whom 56 were positive for COVID-19 while 117 were negative for COVID-19. COVID-19 patients admitted with neurological disease, including stroke, have a significantly higher in-hospital mortality, incident delirium and higher disability than patients without COVID-19.
Publication date / reference: 15/04/20 Yin R et al. Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019. J Med Virol.
Summary: Single case report of a patient presenting with altered consciousness and some indications of contextually dissociated speech. Both lower limbs showed positive ankle clonus and extensor reflexes. Positive for the Brudzinski sign and the straight leg raise test. Treated with antivirals. LP was negative for 2019-nCoV nucleic acid test.
Publication date / reference: 15/04/2020 Helms J et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med.
Summary: Prospective observational study of Neurological features in a series of 58 of 64 consecutive patients. Positive findings on CAM-ICU (65%), agitation (69%), corticospinal tract signs (67%), dysexecutive syndrome (36%). Also summarises MRI brain findings(♦).
Publication date / reference: 10/04/2020 Mao L et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol.
Summary: Retrospective case series of 214 patients. Those with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5.7%) and impaired consciousness (14.8%)(♦).
Other Clinical Syndromes
Publication date / reference: 23/04/2021 Coll C, Tessier M, Vandendries C, Seror P. Neuralgic amyotrophy and Covid 19 infection: 2 cases of spinal accessory nerve palsy. Joint Bone Spine.
Summary: This small case series (n=2) reported cases of neuralgic amyotrophy, also known as Parsonage Turner Syndrome, related to spinal accessory nerve palsy following COVID-19 infection. Both patients showed spinal accessory nerve axonal lesions on electrodiagnostic examinations within 6 months of COVID-19 infection onset. The authors concluded that COVID-19 infection may have triggered neuralgic amyotrophy.
Publication date / reference: 30/04/2021 van Kempen et al. SARS-CoV-2 Antibodies in Adult Patients With Multiple Sclerosis in the Amsterdam MS Cohort. JAMA Neurol.
Summary: This prospective cohort study aimed to test for SARS-CoV-2 antibodies in a large MS cohort to evaluate asymptomatic infections and immunological responses to COVID-19. The authors collected blood samples for SARS-CoV-2 antibody measurements with a total antibody assay and patients’ characteristics and clinical data from digital questionnaires and the medical files. They found that (n=546) patients had mean [SD] age = 46.9 [12.1] years, 71.1% women, 11.7% SARS-CoV-2 antibodies detected.
Nine patients who were antibody positive (14%) did not experience any COVID-19 symptoms. The most frequently reported symptom in those positive for SARS-CoV-2 antibodies was a loss of taste and/or smell (47%), while only 2.9% without SARS-CoV-2 antibodies reported these symptoms. 74.2% were receiving disease-modifying therapy. In these, SARS-CoV-2 antibodies were less prevalent in patients using injectable drugs (interferon β and glatiramer acetate) than patients with other treatments.The median SARS-CoV-2 antibody response in patients treated with ocrelizumab was lower in comparison with other patients. All patients taking ocrelizumab were B-cell depleted. None of these patients experienced hypogammaglobulinemia at that time. They concluded that B-cell depletion could influence SARS-CoV-2 antibody production in patients with MS. This holds important consequences for humoral immunity after COVID-19 infection and possibly vaccination.
Publication date / reference: 01/05/2021. Sara Esmaeili et al. Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD. BMC Neurol.
Summary: This case series study aimed to assess the incidence rate and course of COVID-19 in patients with MS/NMOSD patients undergoing treatment with Rituximab. Data was collected through a web-based questionnaire, which assessed reported walking disability, total number of Rituximab infusions received, delayed injections, occurrence of any relapse, and the use of corticosteroids during the pandemic. 258 patients with MS were enrolled in the study. Results revealed a higher incidence of COVID-19 infection or serious illness, and a higher fatality in patients using Rituximab compared to patients not receiving DMARDs.
Publication date / reference: 14/042021 Garcia et al., Neurological manifestations of patients with mild-to-moderate COVID-19 attending a public hospital in Lima, Peru eNeurologicalSci
Summary: Authors of this study aimed to determine the prevalence and characteristics of the most common neurological manifestations in Peruvian patients with mild-to-moderate COVID-19. This was a single-center prospective, cross-sectional study at an isolation center functioning as a public acute-care hospital during the COVID-19 pandemic in Lima. Convenience sampling of patients with acute COVID-19 infection and mild-to-moderate respiratory symptoms was done. Of 199 patients with mild-to-moderate COVID-19 enrolled in this study, 83% presented with at least one neurological symptom (mean symptom duration 8 +/− 6 days). The most common neurological symptoms were headache (72%), hypogeusia or ageusia (41%), hyposmia or anosmia (40%) and dizziness (34%).
Publication date / reference: 15/04/2021 Thakur et al., COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital. Brain.
Summary: This study presents the clinical, neuropathological and molecular findings of 41 consecutive COVID-19 patients who died and underwent autopsy. Neuropathological examination revealed hypoxic and ischaemic changes in all brains, microglial activation and atherosclerosis. 44% of patients contained pathologies of neurodegenerative diseases, not unexpected given the age range of our patients. The levels of detectable virus in COVID-19 patients were very low and did not correlate with the histopathological correlations.
Publication date/reference: 15/04/2021 Czarnowska et al., Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies – the Polish experience. Neurol Neurochir Pol.
Summary: This study aimed to report the course and outcome of SARS-CoV-2 infection in MS patients treated with DMTs. Most MS patients had a favourable course of SARS-CoV-2 infection, hospitalisation rates and mortality rates were not higher in the MS cohort compared to the general Polish population.
Publication date/ reference: 12/04/2021. Köken et al. Impact of COVID-19 on serum melatonin levels and sleep parameters in children. Turk J Med Sci.
Summary: This case-control study compared melatonin levels and sleep patterns in paediatric patients with COVID-19 (n=80) with children with non-specific upper respiratory viral infections (n=26). The authors found that serum melatonin levels were above normal range in all patients with no significant difference between the COVID-19 and the control group (136.7 pg/mL and 172.6 pg/mL, respectively, p=0.16). There was no difference in sleep patterns. Based on the melatonin levels above the normal range and mild COVID-19 phenotype in children, the authors suggested that melatonin may play a protective role in COVID-19.
Publication date / reference: 07/2021. Systemic Inflammation Is Associated With Neurologic Involvement in Pediatric Inflammatory Multisystem Syndrome Associated With SARS-CoV-2. Neurol Neuroimmunol Neuroinflamm.
Summary: This cross-sectional study reports neurologic features of Pediatric Inflammatory Multisystem Syndrome associated with COVID-19 (PIMS-TS). Clinical features and short-term outcomes were reported in 75 children identified retrospectively from patient notes with PIMS-TS from March-June 2020 in a large children’s hospital. Systemic inflammatory and prothrombotic markers were found to be higher in the 9 patients with neurologic symptoms, and were higher still in those patients who did not fully recover. It is concluded that measuring such biomarkers may be helpful in facilitating the treatment of inflammation.
Publication date / reference: 4/2021. Garcia-Monco et al. Neurologic Manifestations in a Prospective Unselected Series of Hospitalized Patients With COVID-19. Neurol Clin Pract.
Summary: This cross-sectional study reports the prevalence of neurological manifestations associated with COVID-19, amongst a cohort of 100 patients. 88% of the cohort were found to have at least one neurological manifestation. The most common of these were anosmia or dysgeusia (44%), myalgia (43%), and dizziness (36%).
Publication date / reference: 4/2021. Anand et al. Neurologic Findings Among Inpatients With COVID-19 at a Safety-net US Hospital. Neurol Clin Pract.
Summary: This was a retrospective case notes review of 77 patients at a single centre, with PCR-confirmed SARS-Cov-2 infection. The most common neurological symptoms were altered mental status (n = 39), fatigue (n = 18), and headache (n = 18). 20% of patients suffered an ischaemic stroke (n = 15).
Publication date / reference: 10/03/2021 Yildiz et al. Clinical, Neurophysiological and Neuroimaging Findings of Critical Illness Myopathy After COVID-19. Cureus.
Summary: This paper reports the clinical, neurophysiological and neuroimaging findings indicative of critical illness myopathy in three patients with COVID-19. All three had long stays in ICU and mechanical ventilation. It provides some guidance on the expected findings which may help diagnose critical illness myopathy alongside muscle biopsy.
Publication date / reference: 03/04/2021 Hosp et al., Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19
Summary: In this prospective cohort study, the authors assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions.
Publication date / reference: 30/03/2021 Tang et al., Aberrant cytokine expression in COVID-19 patients: Associations between cytokines and disease severity. Cytokine.
Summary: This retrospective study of 71 hospitalised COVID-19 patients sought to investigate clinical and laboratory characteristics, in relation to disease severity. IL-6 and IL-10 cytokine levels were significantly higher in the critically severe patients and also were closely correlated to dyspnea and dizziness (P < 0.05).
Publication date / reference: 30/03/2021 Gu et al. A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors. Endocrine.
Summary: This study aimed to investigate the potential risks of SARS-CoV-2 infection on the impairment of pituitary glands and the development of pituitary neuroendocrine tumors (PitNETs). The authors obtained PitNETs tissues from (n=114) patients, and normal pituitary gland tissues were obtained from the autopsy. The pituitary hormones between 43 patients with SARS-CoV-2 infection were compared with 45 healthy controls. They found that pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum ACTH was significantly increased in COVID-19 compared to controls, but was decreased in critical compared to non-critical patients. They concluded that this study revealed a potential impact of SARS-CoV-2 infection on corticotroph cells and adenomas.
Publication date / reference: 03/03/2021 Rodríguez et al. COVID-19-Related Neuropsychiatric Symptoms in Patients With Alcohol Abuse Conditions During the SARS-CoV-2 Pandemic: A Retrospective Cohort Study Using Real World Data From Electronic Health Records of a Tertiary Hospital. Front Neurol.
Summary: In this study, the first of its kind that we are aware of, the authors looked at the effects of alcohol consumption on the clinical course of hospitalised covid-19 patients. Alcoholic patients were more likely to spend longer in hospital, and were over three times more likely to manifest neuropsychiatric complications. These were mainly delirium symptoms (disorder of consciousness, confusion) which you might expect from an alcoholic inpatient group regardless of covid-19, and the authors did not compare to an alcoholic non-covid group.
Publication date / reference: 23/03/21 Bax et al. Clinical and neurophysiological characterization of muscular weakness in severe COVID-19. Neurol Sci.
Summary: Bax et al report clinical and elcetroneuromyographic (ENMG) characteristics of 8 patients with COVID-19 requiring intubation in intensive care. The authors found neuromuscular involvement in 6/8 patients, consisting of critical illness polyneuropathy, myopathy, polyneuromyopathy as well as ICU-acquired weakness. These patients tended to have higher levels of IL-6 at admission and longer duration of intubation.
Publication date / reference: 16/03/2021 Amanat et al. Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study BMC Neurol
Summary: In this multicenter prospective clinical study, the authors aimed to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. 873 participants were included. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, comorbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality.
Publication date / reference: 19/03/2021 Ulnar Neuropathy After Intermittent Prone Positioning for COVID-19 Infection: A Preliminary Report of 3 Cases. JBJS Case Connect.
Summary: This case series of three patients presents ulnar neuropathy in association with severe COVID-19 and porning. They postulate the natural progression of the disease and need for proning contribute to this finding and conservative management improves symptoms.
Publication date / reference: 19/03/21. Yan et al. Effects of SARS-CoV-2 infection on neuroimaging and neurobehavior in neonates. World J Pediatr.
Summary: The authors compared five newborns who were infected with SARS-CoV-2 with 15 non-infected babies. Reflex and orientation/behavior scores were lower in the infected group than in the control group.
Publication date / reference: 02/2021. Goel et al. Neurological Manifestations of COVID-19: A Series of Seven Cases. Indian J Crit Care Med.
Summary: Goel and colleagues present a series of seven cases of patients presenting with neurological manifestations of COVID-19 (PCR-confirmed). The cases presented with altered sensation (n = 2), a recent history of pyrexia (n = 2), paraparesis (n = 2), hemiplegia (n = 1) and loss of consciousness (n = 2). Of the patients who were unconscious, one has a history of generalised weakness and the other had a one day history of dyspnoea. Aside from this patient, no other patients had respiratory symptoms. The patients were diagnosed with cerebrovascular accident (n = 3), CNS infection (n = 2) and Guillain-Barre syndrome (n = 2).
Publication date / reference: 06/03/21. Gennaro et al. Quadriparesis caused by retropharyngeal and epidural abscess in COVID-19 patients. Neurol Sci.
Summary: The authors report two cases of retro-pharyngeal abscesses extending into the epidural space and causing spinal cord compression and quadriparesis, in association with a positive test for SARS-CoV-2.
Publication date / reference: 28/02/2021 Jidigam et al. Histopathological assessments reveal retinal vascular changes, inflammation and gliosis in patients with lethal COVID-19. medRxiv.
Summary: This comparative analysis aimed to assess the histopathological changes of the retina and choroid to determine long term sequelae of COVID-19. They used 11 donor eyes from COVID-19 patients and were age-matched with controls who tested negative for SARS-CoV-2. Examination revealed haemorrhagic spots and vitreous debris compared to controls, a non-statistical increase in retinal thickness as well as changes in retinal microvasculature, increased inflammation, and gliosis on histological analysis. Choroidal vasculature also showed changes of inflammation.
Publication date / reference: 26/2/2021 Clark et al. Abnormal movements in hospitalized COVID-19 patients: A case series. J Neurol Sci.
Summary: This case series aimed to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation. The authors retrospectively analyzed (n=50) patients with confirmed Covid-19 hospitalized at tertiary medical care center who underwent acute inpatient neurology consultation. They found that 22.0% were evaluated for abnormal movements (54.5% myoclonus). Additionally, two patients had seizures, while two had tremor. They concluded that abnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.
Publication date / reference: 2/3/21 Medrinal et al. Muscle weakness, functional capacities and recovery for COVID-19 ICU survivors. BMC Anesthesiol.
Summary: Medrinal and colleagues conducted a cross-sectional study of COVID-19 ICU survivors (n=23) across two tertiary centres. At the time of extubation, participants were screened for respiratory and limb muscle strength. The ICU mobility scale was performed at ICU discharge and walking capacity was self-evaluated by patients 30 days following extubation. 16 participants has limb weakness, with 6 also having respiratory muscle weakness. 7 participants were unable to walk 100 m, 30 days post-extubation.
Publication date / reference: 4/03/2021 Specific Susceptibility to COVID-19 in Adults with Down Syndrome Illouz et al. Neuromolecular Med.
Summary: Individuals with Down syndrome (DS) appear to have a significantly higher risk of developing severe symptoms of infectious diseases, including those related to COVID-19, because of their complex trisomy and consequent numerous immune impairments, which render them susceptible to infections. the influence of human leukocyte antigen (HLA) gene polymorphisms on SARS susceptibility, pathogenesis, and outcome has been investigated in a number of studies. Some HLA alleles have been significantly associated with susceptibility to SARS and/or disease severity in various populations.
Publication date / reference: 25/02/2021 Becker et al. Intracranial Hypertension in Multisystem Inflammatory Syndrome in Children (MIS-C). J Pediatr.
Summary: This case series assesses four patients with Multisystem Inflammatory Syndrome in Children (MIS-C) secondary to SARS-CoV-2 that developed intracranial hypertension as a result. They discuss the incidence of neurological complications seen in MIS-C poor description of these complications in the literature. They further discuss the unique management of these cases and describe their disease course.
Publication date / reference: 25/02/2021 Canavero et al. Acute myelopathies associated to SARS-CoV-2 infection: viral or immune-mediated damage? Travel Med Infect Dis.
Summary: This case series of three patients assesses the role of COVID-19 in the aetiology of the myelopathies described and the neutrotropic potential of SARS-CoV-2. They methodically describe the three cases including their biochemistry, radiology and neurophysiology.
Publication date / reference: 18/02/2021. Celik et al. Evaluation of cochlear functions in infants exposed to SARS-CoV-2 intrauterine. Am J Otolaryngol.
Summary: In this study, cochlear function of infants whose mother was diagnosed with COVID-19 (N=37) during pregnancy was compared with control (N=36). The investigators found that transient evoked otoacoustic emission (TEOAE) showed a statistically significant difference between the two infant groups, those infants whose mother had COVID-19 during pregnancy showed insufficiency in medial olivocochlear efferent system. Leading the author to call for cochlear function examination in infants whose mothers had COVID-19.
Publication date / reference: 03/02/2021 de Sousa et al. SARS-CoV-2 and hearing: an audiometric analysis of COVID-19 hospitalized patients. J Otol.
Summary: This cohort study aimed to evaluate hearing function in moderate to severe COVID-19 patients with no prior hearing abnormalities who had been referred to a tertiary referral centre. They assessed 120 ears from 60 patients and matched them with controls. They found a statistical significance in mean auditory thresholds from 1000Hz to higher frequencies were lower than that compared to controls, even when confounding for age, gender, and various comorbidities
Publication date / reference: 15/02/2021 Caronni et al. Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study. Brain Inj.
Summary: In their report Caronni et al. present a case series of 6 patients with SARS-CoV-2 infection out of 11 patients with severe acquired brain injury, hospitalised in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy). No fatalities occurred during the study and confirmed COVID-19 patients required only low oxygen flow. However, the authors reported that the clearance time of SARS-CoV-2 was longer than usually reported (median > 50 days).
Publication date / reference: 02/02/21. Heidbreder et al. Video-polysomnographic findings after acute COVID-19: REM sleep without atonia as sign of CNS pathology?. Sleep Med.
Summary: This study examined sleep disorders in COVID-19 patients. The 11 subjects underwent video-polysomnography at an average of 4.2 (SD=1.3) months after SARS-CoV-2 infection diagnosis. At 60 days, persistent breathing issues were present in seven of 11 patients. Four patients showed REM sleep without atonia and two additionals showed an RWA index within the highest range of normality. The authors concluded that sleep disorders are common after COVID-19.
Publication date / reference: 28/01/21. Akinci et al. Relationship between sleep quality and the psychological status of patients hospitalised with COVID-19. Sleep Med.
Summary: This study explored sleep and its relationship to the psychological status of patients hospitalised with COVID-19. 189 patients were enrolled and their sleep quality and related factors including demographics analysed. The Pittsburgh Sleep Quality Index (PSQI) was used as well as the Hospital Anxiety-Depression Scale (HADS). 54% of patients had a PSQI score of >4 and 46% had scores <5. In the group with poor sleep quality (>4), duration of hospitalisation and depression rate were higher. The authors called for attempts to improve sleep quality among COVID-19 inpatients.
Publication date/reference: 11/02/2021 Moonis et al., Radiologic Assessment of the Sinonasal Tract, Nasopharynx and Mastoid Cavity in Patients with SARS-Cov-2 Infection Presenting with Acute Neurological Symptoms. Ann Otol Rhinol Laryngol.
Summary: This was a retrospective case series (n=55), investigating radiologic involvement of nasal cavity, nasopharynx, paranasal sinuses, and mastoid cavity in COVID-19 patients who presented with acute neurological symptoms.
Publication date / reference: 09/02/2021 Goldstein et al. The prevalence and impact of pre-existing sleep disorder diagnoses and objective sleep parameters in patients hospitalized for COVID-19. J Clin Sleep Med
Summary: This retrospective study in 572 patients, who were hospitalized for COVID-19 in University of Michigan Hospital System demonstrated that around 113 (19.8%) had obstructive sleep apnea, 4 (0.7%) had central sleep apnea, 5 (0.9%) had hypoventilation, 63 (11.0%) had insomnia and 22 (3.9%) had restless leg syndrome or periodic limb movement disorder. Sleep disorders did not contribute significantly to outcomes.
Publication date / reference: 03/02/2021 de Sousa et al. SARS-CoV-2 and hearing: an audiometric analysis of COVID-19 hospitalized patients J Otol
Summary: The main objective was to determine whether SARS-CoV-2 may affect auditory function in clinically ill COVID-19 patients. 120 ears from 60 patients were enrolled. Patients with COVID-19 showed worse mean auditory thresholds starting from 1000 Hz through higher frequencies, when compared to controls. Results from the study suggest that SARS-CoV-2 may affect hearing in COVID-19 patients with moderate-severe disease.
Publication date / reference: 06/02/2021. Espindola et al. Inflammatory cytokine patterns associated with neurological diseases in COVID-19. Ann Neurol.
Summary: In this case series study (N=48) the investigator analysed inflammatory markers in the CSF and serum of SARS-CoV2 positive patients presenting with various neurological conditions headache (n=12), encephalopathy (N=22) and inflammatory neurological diseases ( (N=14). The studies found distinct patterns of increased inflammatory markers in the CSF and serum in patients presenting with different neurological conditions. Inflammatory neurological diseases (ADEM, encephalitis, meningitis, meningoencephalitis, acute myelitis and neuromyelitis optica) were associated with increased levels of IL-2, IL-4, IL-6, IL-10, IL-12 CXCL8 and CXCL10 in the CSF. Encephalopathy was associated with high serum levels of IL-6, CXCL8 and active TFG-b1. However refractory headache was not associated with increased CSF level of inflammatory cytokines.
Publication date / reference: 08/1/21. Gonzalez-Martinez et al. Headache during SARS-CoV-2 infection as an early symptom associated with a more benign course of disease: a case-control study. Eur J Neurol.
Summary: This case-control study included hospitalised patients with COVID-19 pneumonia in March 2020. Of 379 patients with SARS-CoV-2, 13% developed headaches. Headache was found to be associated with a younger age, reduced mortality and less comorbidities. Moreover, headache was directly associated with D-Dimer and creatinine levels, high flow nasal cannula use and arthromyalgia and low levels of C-reactive Protein. The authors concluded that headache can appear as an early COVID-19 symptom and urged further research into the underlying pathological mechanisms.
Publication date / reference: 08/01/21. Ghaffari et al. Neurological features and outcome in COVID-19: dementia can predict severe disease. J Neurovirol.
Summary: This retrospective study conducted in Tehran evaluated all adult patients hospitalised with SARS-CoV-2 infection from March 2020 to April 2020. Among 361 inpatients, 31 had neurological complications including encephalopathy (3%), ischaemic stroke (2.2%), intracerebral haemorrhage (1.1%), subarachnoid haemorrhage (0.3%), multiple sclerosis relapse (0.3%) and Guillain-Barré syndrome (0.3%). No significant relationship between neurological complications and severity of COVID-19 was found. The authors did find that dementia was associated with severe COVID-19 disease, however. Patients with a history of dementia were 1.28 times more likely to develop severe COVID-19 disease. The authors proposed neuroinflammation as a potential pathological mechanism and proposed further research in order to clarify the observed increased risk of severe illness.
Publication date / reference: 04/01/2021 Altunisik et al. Neurological symptoms in COVID-19 patients. Bratisl Lek Listy.
Summary: Altunisik et al describe the neurological and musculoskeletal symptoms of 51 patients hospitalised with COVID-19. The authors grouped the patients into mild (40/51) and severe (11/51) disease. They found that neurological symptoms were detected in 16 (31.37 %) patients, the most common of which was headache (n: 9, 17.65 %). Muscle injury was detected in 10 (19.61 %) patients. Comparing the two groups, there were no significant differences in neurological or musculoskeletal symptoms.
Publication date / reference: 04/01/2021 Tuzun et al. Assessment of musculoskeletal pain, fatigue and grip strength in hospitalized patients with COVID-19. Eur J Phys Rehabil Med.
Summary: This is a cross-sectional, single-center case series describing musculoskeletal symptoms in 150 adult patients hospitalised with COVID-19. Of these, 103 patients (68.7%) were categorised as non-severe and 47 patients (31.3%) as severe. The authors found that the most common musculoskeletal symptom was fatigue (133 [85.3%]), followed by myalgia (102 [68.0%]), arthralgia (65 [43.3%]) and back pain (33 [22.0%]). Arthralgia, most commonly of the wrist (25 [16.7%]), was significantly higher in the severe group. Scores indicative of severe myalgia, assessed using the numerical rating scale (NRS), were found across both the severe and non-severe groups. The severity of fatigue was assessed using the Visual Analog Scale and Chalder Fatigue Scale (CFS). The physical fatigue severity score was significantly higher in the severe group when compared to the non-severe group, whereas there was no significant difference in the mental fatigue score. Female patients seemed to have poorer grip strength in severe disease, which was associated with raised CRP, ferritin and LDH levels. No difference in grip strength was observed in males. The authors suggest that these symptoms are indicative of severe ischemic myalgia, regardless of disease activity.
Publication date / reference: 08/01/2021. Huang et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet.
Summary: In this study, authors did an ambidirectional cohort of patients with confirmed COVID-19 who had been discharged between Jan 7, 2020, and May 2. Patients that died before follow-up or having other syndromes like dementia, psychotic disorders, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile due to diseases such as stroke or pulmonary embolism etc. were excluded. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients.
Publication date / reference: 17/12/20. Planchuelo-Gómez et al. Deep Phenotyping of Headache in Hospitalized COVID-19 Patients via Principal Component Analysis. Front Neurol.
Summary: The authors of this cross-sectional study aimed to use machine learning to examine the phenotype of headache in hospitalised patients with COVID-19 (n=106). Intensity of reported pain and disability due to headache were with female sex, presence fever and haematological derangement (plateletes, leukocytosis). Based on Generalized Linear Models and Principal Component Analysis, the authors distinguished two distinct headache phenotypes. The first phenotype included an association with migraine symptoms and lymphopenia, although it is unclear if there is a causal link within this association. The second phenotype associated tension-type headache symptoms with milder COVID-19 laboratory features.
Publication date / reference: 2/12/20. Daniel Natera-de Benito et al. COVID-19 in children with neuromuscular disorders. J Neurol.
Summary: This study aimed to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. This was investigated with the use of a registry set up by the Spanish Paediatric Neurology Society looking at children with neuromuscular conditions and laboratory confirmed SARS-CoV-2 infection. They concluded that COVID-19 may not be as severe in this populations potentially due to young age.
Publication date / reference: 05/11/2020 Groiss et al. Prolonged Neuropsychological Deficits, Central Nervous System Involvement, and Brain Stem Affection After COVID-19—A Case Series. Front Neurol.
Summary: Here the authors present four patients who were severally unwell with covid-19, but otherwise were a heterogenous group. Three showed evidence of acutely impaired cognition, and they all had PNS conduction abnormalities on electrophysiological testing. The authors also claim one had electrophysiological evidence of brainstem involvement via testing of the blink reflex. The conclusions and significance of this study are hard to decipher.
Publication date / reference: 05/11/20. Hwang et al. Acute Seizures Occurring in Association With SARS-CoV-2. Front Neurol.
Summary: The authors report four cases of seizures occurring in association with in COVID-19. Each case of seizure occurred at distinct time points of the disease with different underlying pathology, including elevated inflammatory changes; cortical venous thrombosis, hypertension with end stage renal disease and PRES and necrotizing encephalopathy. The study highlights that etiology of seizures associated with SARS-CoV-2 infections can be heterogeneous and the authors called for further research in this area.
Publication date / reference: 26/11/2020 Needham et al. Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol.
Summary: Needham et al present a case series focusing on 11 patients seen in a post-COVID-19 follow-up clinic. Out of 69 patients, these 11 (16%) had mononeuritis multiplex. All 11 patients required mechanical ventilation for an average of 36 days. The neuropathies were noted following withdrawal of sedation, suggesting that these nerve injuries developed during the period of ventilation. Interestingly, there was no EMG evidence of myopathy. The authors note that these neuropathies are clinically similar, to some extent, to vasculitic neuropathies. This could be related to endotheliopathy from the “cytokine storm” or microthrombi occurring in COVID-19.
Publication date / reference: 21/10/2020. Akshay Avula et al. Incidence of Thrombotic Events and Outcomes in COVID-19 Patients Admitted to Intensive Care Units. Cureus.
Summary: This study aimed to describe the incidence and risk factors leading to thrombotic complications and mortality rates among COVID-19 patients admitted to ICU. Data was analysed from a large database called TriNetX, and the authors concluded that high risk groups for severe disease were being male, African American, and over the age of 65.
Publication date / reference: 10/11/2020 Victorino et al. COVID-19 and stroke: red flags for secondary movement disorders? eNeurologicalSci
Summary: This letter discusses the evidence in the literature suggesting that neurological complications are common in COVID-19 infection. They conclude that hypercoagulability from the amplified inflammatory immune response can predispose these patients to thromboembolic complications. The authors also suggest that we should be aware of movement disorders that can occur as a result. They talk about several examples: post-stroke movement disorders, myoclonus, parkinsonian symptoms.
Publication date / reference: Dec 2020. Lacomis. What is in the Myopathy Literature? J Clin Neuromuscul Dis.
Publication date / reference: 20/11/20. Patients recovering from COVID-19 pneumonia at a sub-acute admissions unit exhibit profound muscular weakness: a case series. Eur J Phys Rehabil Med
Summary: This is a case series of 14 patients recovering from COVID-19 who manifested with generalised muscular weakness and consequently underwent neurophysiological investigation. The authors detected polyneuropathy in 12 patients and the remainder were diagnosed with cerebrovascular accident and neuromyelitis optica. The majority of patients with polyneuropathy were mechanically ventilated and diagnosed with critical illness polyneuropathy (7/12). Interestingly, none of the patients were at prior increased risk of developing neuropathy (e.g., from diabetes). The predominant pattern of damage was axonal and asymmetric.
Publication date / reference: 15/11/20. COVID-19 cognitive deficits after respiratory assistance in the subacute phase: a COVID-rehabilitation unit experience. MedRxiV (pre-print, not peer-reviewed).
Summary: This prospective study (pre-print) evaluated the cognitive function of 87 patients admitted to a COVID-rehabilitation unit using a comprehensive battery of cognitive assessment tools (including MMSE, MoCA and others). The participants were all defined by having sub-acute COVID-19. The authors found that 80% had neuropsychological deficits (MoCA and MMSE) and 40% had mild-to-moderate depression (Hamilton Rating Scale). Based on subgroup analyses, the authors found that the presence of cognitive deficit could be influenced by modality of ventilation required but was mostly affected by age.
Publication date / reference: 20/11/20 Beaud et al. Pattern of cognitive deficits in severe COVID-19. J Neurol Neurosurg Psychiatry.
Publication date / reference: 9/11/2020 Shahbaznejad et al. Clinical characteristics of 10 children with a pediatric inflammatory multisystem syndrome associated with COVID-19 in Iran. BMC Pediatr.
Publication date / reference: 14/11/2020. Murat et al. Clinical presentations of pain in patients with COVID-19 infection. Ir J Med Sci.
Summary: Retrospective cross-sectional study of confirmed COVID-19 patients (N=210) , reports a high prevalence of myalgia/arthralgia and headache (69.17% and 50.37%).
Publication date / reference: 04/11/2020 Caronna et al. Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution. Cephalalgia.
Summary: This prospective study aims to define the clinical data and inflammatory biomarkers of COVID-19 patients admitted via the emergency room (n=130) with and without headache. The authors found that 74.6% (97/130) had headaches and were more likely to have anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Headaches seemed to be predictive of a shorter clinical course of COVID-19. In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. The authors found that these headaches can persist after the resolution of COVID-19. The authors hypothesise that pathophysiologically, migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia.
Publication date / reference: 04/11/2020 López et al. Phenotypic characterization of acute headache attributed to SARS-CoV-2: An ICHD-3 validation study on 106 hospitalized patients. Cephalalgia.
Summary: This is a cross-sectional study which aims to characterise the phenotype of headache attributed to the SARS-CoV-2 infection and to test the International Classification of Headache Disorders (ICHD-3) phenotypic criteria for migraine and tension-type headache. The authors included patients hospitalised with a positive SARS-CoV-2 test (n=580). They found that headache was the first symptom in 26% of patients. This tended to have severe intensity (64%), frontal predominance (83%) and a pressing quality (75%). Most patients fulfilled ICHD-3 criteria for headache attributed to systemic viral infection (as assessed by two neurologists); however, the phenotype might resemble migraine in 25% and tension-type headache in 54% of the patients.
Publication date / reference: 4/11/20. Rehab Magdy et al. Characteristics of headache attributed to COVID-19 infection and predictors of its frequency and intensity: A cross sectional study. Cephalalgia.
Summary: This cross sectional study aimed to study the characteristics of headache attributed to COVID-19 infection and predictors of its severity. The authors concluded that healthcare providers of COVID-19 patients need to be aware of frequency and intensity predictors of COVID-19 related headache: Primary headache disorders, fever, dehydration, and comorbidities.
Publication date / reference: 4/11/2020. Marcus Tulius T Silva et al. Isolated intracranial hypertension associated with COVID-19. Cephalalgia.
Summary: This cross sectional study aimed to describe the characteristics of headache and the cerebrospinal fluid (CSF) profile in COVID-19 patients, highlighting the cases of isolated intracranial hypertension. The authors concluded that in a significant proportion of COVID-19 patients, headache was associated with intracranial hypertension in the absence of meningitic or encephalitic features. Further studies assessing coagulopathy associated with COVID-19 are suggested to further clarify this.
Publication date / reference: 4/11/20. Wang et al. Impact of Covid-19 in pregnancy on mother’s psychological status and infant’s neurobehavioral development: a longitudinal cohort study in China. BMC Med.
Summary: Wang and colleagues report the findings of a longitudinal single arm-cohort study conducted from the 1st of May to the 31st of July 2020 which investigated the impact of SARS-Cov-2 infection during pregnancy on maternal psychological state and infant neurodevelopment. A cohort of 72 pregnant women with COVID-19 completed a series of follow up surveys up until 3 months following delivery or termination of pregnancy. Alongside these following surveys, Wang and colleagues collected data from medical record regarding COVID-19 status, delivery or abortion, analysis of maternal or neonatal specimens, data from questionnaires assessing separation between the mother and baby, neonatal feeding, maternal mental state and neurobehavioural disorders in the infant. 22.2% of patients experienced post-traumatic stress disorder or depression three months following delivery or abortion. Among the 57 live births, one neonate had PCR confirmed COVID-19 but this was later negative on subsequent tests. The median duration of maternal separation was 35 days. After the termination of maternal quarantine, 49.1% of mothers chose to prolong separation with their infant. After adjusting for prematurity, neonatal sex, neonatal intensive care admission and the mother’s COVID-19 condition, the number of separation days were found to be negatively associated with three developmental domains: communication, gross motor and personal-social.
Publication date / reference: 7/11/2020. Codeluppi et al. Facial palsy during the COVID‐19 pandemic. Brain Behav.
Summary: This retrospective cohort study aimed to compare the incidence and clinical features of individuals presenting in emergency rooms (ER) with facial palsy during the Italian COVID‐19 outbreak and in the same period. The authors reviewed the medical records for all accesses to the six ER in Italy, during the first phase of the COVID‐19 pandemic to identify all cases of diagnosed facial palsy. Clinical information was retrieved for each patient and compared with that of facial palsy cases presenting in 2019. They found that 38 patients presented to provincial ERs for facial palsy, there were 22 cases, for an incidence rate ratio of 1.73 for the 2020 cohort. Eight patients (21%) of them presented with active or recent symptoms consistent with COVID‐19 infection; one was tested and resulted positive for SARS‐CoV‐2. Patients were younger than those of the previous year and manifested a longer lag between symptoms onset and ER presentation. They concluded that there was a higher occurrence of facial palsy during the COVID‐19 outbreak compared to the same period of the previous year.
Publication date / reference: 12/2020 Almeria et al. Cognitive profile following COVID-19 infection: Clinical predictors leading to neuropsychological impairment. Brain Behav Immun Health.
Summary: In their prospective cohort study, Almeria et al. assessed thirty-five patients who had recently been discharged from hospital with covid-19. Interestingly, they decided to exclude older patients (>60) in order to try and reduce the confounding effect of pre-existing cognitive disorders. Perhaps unsurprisingly, patients with markers of severe infection scored worse on the Global Cognitive Index, with between 5-10% having significant levels of impairment on particular cognitive domains. This poorer performance on cognitive testing was also reflected by increased levels of anxiety and depression. This is a nicely designed small prospective study, but is limited by lack of follow-up and the exclusion criteria.
Publication date / reference: 27/10/2020 Espíndola et al.Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development. Int J Infect Dis.
Summary: This multicentre study in Brazil evaluated the cerebrospinal fluid of 58 patients with both COVID-19 and neurological symptoms. Neurological symptoms included headache, encephalopathy, inflammatory neurological diseases and GBS. Only two patients had SARS-COV-2 RNA detectable in their CSF. One-third of patients showed high ICP (≥ 25 mmH2O), although this characteristic was not associated with a specific neurological picture. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. Overall the CSF findings were very diverse but the authors argue that they indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the inflammation promoting neuronal injury.
Publication date / reference: 22/10/2020 Amezcua et al. COVID-19-Induced Neurovascular Injury: a Case Series with Emphasis on Pathophysiological Mechanisms. SN Compr Clin Med.
Summary: This case series describes the neurovascular complications of COVID-19 in 5 patients with COVID-19 including: middle cerebral artery infarction, acute intraparenchymal hemorrhages and a a mixed mononuclear inflammatory infiltrates. The authors discuss the potential underlying mechanisms leading to these complications with a focus on coagulation abnormalities in COVID-19 and neurological injury.
Publication date / reference: 15/10/20. Pirraglia et al. Retinal involvement and ocular findings in COVID-19 pneumonia patients. Sci Rep.
Summary: Cross-sectional study of COVID-19 patients (n=46) from one intensive care unit. The authors found 1 case of unilateral posterior chorioretinitis and 3 cases of bilateral conjunctivitis all had negative results for SARS-Cov2 as origin of infection. The findings led the authors to conclude there is absence of retinal involvement in SARS-Cov-2 pneumonia patients.
Publication date / reference: 13/10/20. Nasuelli et al. Critical illness neuro-myopathy (CINM) and focal amyotrophy in intensive care unit (ICU) patients with SARS-CoV-2: a case series. Neurol Sci.
Publication date / reference: 13/10/20.Uygun et al. Headache characteristics in COVID-19 Pandemic a survey study. J Headache Pain.
Summary: Survey study (n=3458), headache features were investigated in those with COVID-19 (n=262). Regression analysis was used and found bilateral, long lasting headache, resistant to analgesia and having male gender were more frequently in people with COVID -19, in conjunction with anosmia/ageusia and gastrointestinal complains.
Publication date / reference: Sept 2020. Negrini et al. Neuropsychological features of severe hospitalized COVID-19 patients at clinical stability and clues for post-acute rehabilitation. Arch Phys Med Rehabil. (Pre-Print).
Summary: Case series reports the general cognitive function assessment of patients recovering from ARDs following Covid-19 (n=19). 3 patients showed general cognitive decline (MMSE), decline itself showed linear relationship with length of ICU stay. This finding prompted the authors to call for consideration of neuropsychological rehabilitation in a subset of patients treated in ICU for covid-19.
Publication date / reference: 02/10/2020. Lima et al. Peripheral facial nerve palsy associated with COVID-19. J Neurovirol.
Lima et al. present a case series of eight patients with COVID-19 who developed peripheral facial palsy during infection. For three of these patients, facial palsy was the presenting symptom. Seven out of eight patients were treated with steroids and all patients had complete or partial recovery of the symptoms.
Publication date / reference: 11/09/20. Camelo-Filho et al. Myasthenia Gravis and COVID-19: Clinical Characteristics and Outcomes. Front Neurol.
Camerlo-Filho and colleagues report a case series of 15 patients with myasthenia gravis who were admitted to hospital with COVID-19 across four centres in Brazil. The majority of the cohort suffered a severe manifestation of COVID-19, with 13 being admitted to ICU and 11 requiring mechanical ventilation. Four of the patients died. No complications were reported to be associated with administration of intravenous immunoglobulin or plasma exchange therapy.
Publication date / reference: 18/09/20. Antonelle de Marcaida et al. Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) among Patients at a Movement Disorders Center. Geriatrics.
Summary: This study reviewed electronic health records and conducted phone interviews in order to collect demographics and clinical outcomes of patients seen at a movement disorders clinic center who tested positive for SARS-CoV-2 virus. 36 patients were identified, 23 men and 13 women, with a median age of 74.5 years. Primarily, they had diagnoses of idiopathic Parkinson disease (n=22) and atypical parkinsonism (n=7) with the balance having other diagnoses. 27 patients exhibited alteration in mental status and 15 had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, respectively, these were the presenting symptoms of the disease. 67% of the patients required hospitalisation with a mortality rate of 36%. The authors concluded that in patients with movement disorders, the likelihood of hospitalisation and death after contracting SARS-CoV-2 infection was greater than in the general population. Common COVID-19 presentations in these cohorts include altered mental status, generalised weakness or worsening mobility, but not anosmia.
Publication date / reference: 21/09/20. Zhang et al. COVID-19 case fatality and Parkinson’s disease. Mov Disord.
Summary: This study compared COVID-19 case fatality rates in Parkinson’s disease patients with a large, demographically matched population via the TriNetX COVID-19 research network. Among 78,355 COVID-19 patients without PD, 4,290 died compared to 148 of the 694 patients with PD (5.5% vs 21.3% p<0.001). Age and racial composition were taken into account using logistic regression and the authors found that the risk of dying from COVID-19 was significantly elevated in the PD group (OR 1.27, 95% CI 1.04-1.53, p=0.016). The authors urged the development of effective strategies whereby healthcare providers can prevent the transmission of COVID-19 while providing neurological care to patients with PD.
Publication date / reference: Oct 2020. Zhou et al. The landscape of cognitive function in recovered COVID-19 patients. J Psychiatr Res.
Summary: Zhou et al. aimed to evaluate cognitive function in recovered COVID-19 patients, and to explore associations between baseline admission inflammatory markers and post-recovery cognitive function. They recruited 29 right-handed SARS-CoV-2+ patients (mean age 47, range 30-64) and compared their cognitive performance against healthy controls matched for age, sex, and eduction level. To evaluate cognition the authors administered online neuropsychological tests of attention, memory, executive functioning, information processing speed, visuo-spatial processing, and psychomotor function. They found that recovered COVID-19 patients performed more poorly in a test of sustained attention, and there was a possible signal of association between higher baseline CRP and slower post-recovery reaction time in the same test. No other neuropsychological tests showed deficit or correlation with inflammatory markers. Surprisingly the paper does not state how long “post-recovery” the patients were tested, nor the duration between admission blood sampling and cognitive testing, and detailed information on the severity of COVID-19 is lacking. The authors also do not report testing of effort, and even then it could be open to question exactly how one interprets the results of online neuropsychological tests. Despite considerable limitations the study is one of the first to examine long-term cognitive profile in COVID-19 survivors. The authors call for further long-term studies of cognitive function in patients with COVID-19 and its relationship with inflammatory profiles.
Publication date / reference: 12/09/20. Zeidan et al. COVID-19 infection in NMO/SD patients: a French survey. J Neurol.
Summary: The authors conducted a case-series study to describe the prevalence and characteristics of COVID-19 in NMO/SD patients. Among five confirmed or suspected cases and despite ongoing immunosuppressive therapy, severe outcomes were not reported. The study is limited by the very small sample size of infected patients.
Publication date / reference: 10/09/20. Talamonti et al. Spinal epidural abscess in COVID-19 patients. J Neurol.
Summary: This is a retrospective case-series of six patients with spinal epidural abscess and COVID-19. No infective source was discovered in any of the patients, making them primary abscesses, which is the rarest form of abscess. Surprisingly, no significant risk factors for the development of a primary abscess were recorded, with the exception of obesity in two patients. The spinal abscess occurred regardless of the severity of the viral disease, immunologic state, or presence of bacteremia. The authors hypothesised that asymptomatic bacterial contamination and an endotheliitis reaction could have permitted a retrograde bacterial invasion into the epidural space.
Publication date / reference: 04/09/20. Malik et al. Injury-prone: peripheral nerve injuries associated with prone positioning for COVID-19-related acute respiratory distress syndrome. Br J Anaesth.
Summary: The authors describe 11 patients diagnosed with acquired peripheral nerve injury in association with the use of prone positioning for COVID-19-related ARDS. In three cases localisation of the peripheral nerve injury was informed by magnetic resonance neurography, ultrasonography, or both. Their report is a large description of acquired peripheral nerve injury associated with prone positioning for management of ARDS, and one of the first specific to COVID-19.
Publication date / reference: 13/08/20. Fasano et al. Predictors of COVID-19 outcome in Parkinson’s disease. Parkinsonism Relat Disord.
Summary: In this multi-centre cohort study by Fasano and colleagues collected clinical data regarding 117 patients with Parkinson’s disease (PD) with COVID-19 from 21 tertiary centres in 4 countries. COVID-19 diagnosis was confirmed by PCR assay or if the patient had COVID-19 symptoms and had been in contact with a PCR-confirmed case. Amongst the cohort, mortality was 19.7%. Co-occurrence of dementia, hypertension and duration of PD were found to increase mortality risk. These findings indicate that the mortality rate for PD patients is higher than that of the general population.
Publication date / reference: 27/08/20. Masur et al. A Double-Edged Sword: Neurologic Complications and Mortality in Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Severe Acute Respiratory Distress Syndrome at a Tertiary Care Center. AJNR Am J Neuroradiol.
Summary: This observational study aimed to explore neurological complications and mortality in COVID-19 patients on ECMO therapy for ARDS. 12 patients on veno-venous ECMO were included, no patients were on veno-arterious ECMO during the studied time period. The most common comorbid conditions in the cohort were hypertension (6 of 12), type 2 diabetes mellitus (4 of 12) and asthma (4 of 12). The mean duration of ECMO therapy in the cohort was 230.3 hours. On neuroimaging, six patients had critical findings. Most common was intracranial haemorrhage (5 of 12) with associated herniation in four of five patients. All five patients had subarachnoid haemorrhage, four had intraparenchymal haemorrhage and three had intraventricular haemorrhage. Evidence of ischaemic infarctions were seen in two of six, both with concomitant intracranial haemorrhage. In terms of mortality, all four patients with parenchymal bleeds and herniation died. The authors concluded that their analysis had revealed a 50% rate of devastating neurological complications in COVID-19 patients on ECMO for respiratory failure. Despite a small sample size, they urged caution in the use of ECMO and a very low threshold for neuroimaging in this cohort.
Publication date / reference: 26/08/2020 Zerah et al. Clinical characteristics and outcomes of 821 older patients with SARS-Cov-2 infection admitted to acute care geriatric wards. J Gerontol A Biol Sci Med Sci.
Summary: In this multicentre retrospective cohort study in 13 acute COVID-19 geriatric wards, Zerah and colleagues collected data regarding the clinical characteristics and outcomes of 821 geriatric patients with PCR confirmed SARS-Cov-2 infection. 25% of patients had delirium at COVID-19 onset, with delirium being the second most common complication observed. The in-hospital mortality was 31%. This study is strengthened by its large sample size recruited across multiple centres.
Publication date / reference: 17/07/20. Liguori et al. Sleep and wake impairment in patients with SARS-CoV2 infection. Sleep Med.
Summary: The authors present secondary analytic data from a prospective observational study of neurological symptoms in patients hospitalised with non-severe COVID-19. From 103 patients, 51 patients reported sleep impairment and 34 patients complained of daytime sleepiness. The authors conclude that sleep and wake impairment are common complaints in patients with COVID-19. They call for further study with validated sleep questionnaires and scales, or polysomnography, to better characterize sleep impairment in patients with SARS-CoV2 infection.
Publication date / reference: 25/05/20. D’Agostino & Zambrelli. Reply to ‘Delirium, sleep, COVID-19 and melatonin’. Sleep Med.
Summary: Authors respond to a reply to their original study; the reply had strongly suggested that melatonin should be prescribed indiscriminately in COVID-19. In their reply, the authors suggest that melatonin is not prescribed as a rule during all cases of COVID-19, due to lack of supporting evidence that this would be beneficial.
Publication date / reference: 08/08/20. Valdes et al. Special considerations in the assessment of catastrophic brain injury and determination of brain death in patients with SARS-CoV-2. J Neurol Sci.
Summary: The author discuss their experiences declaring brain death in six comatose patients with absent brainstem reflexes. All patients were unresponsive; had absent pupillary, corneal, oculovestibular, cough, and gag reflexes; and did not move their extremities to any stimuli. Issues they encountered included how to weigh unusually high sedation requirements and multiple sedating agents, use of neuromuscular blocking agents to allow ventilation, altered hepatic and renal function potentially changing the pharmacokinetics of drugs, and the difficulties of apnea testing in the context of metabolic derangement and an ongoing requirement for PEEP to maintain airway structure.
Publication date / reference: 16/08/20. Fonseca et al. Epilepsy in time of COVID-19. a survey-based study. Acta Neurol Scand.
Summary: Prospective cross-sectional survey of patients with epilepsy “in the time of COVID-19”. Only five out of 255 had PCR-confirmed viral disease; of these five patients all required hospitalisation, but none reported any change in seizure frequency. Two of these patients died: both were over 70 years old with multiple medical comorbidities.
Publication date / reference: 21/08/20. Martinotti et al. Psychomotor agitation and hyperactive delirium in COVID-19 patients treated with aripiprazole 9.75 mg / 1.3 ml immediate release. Psychopharmacology (Berl).
Summary: In this case series the authors describe 16 consecutive patients with COVID-19 who received treatment with Aripiprazole intramuscular injections for hyperactive delirium. They report that Aripiprazole reduced signs and symptoms of delirium and psychomotor agitation, with high tolerability and no severe adverse effects, in an ITU setting or co-administered with antivirals, hydroxychloroquine and tocilizumab. The authors suggest this experience provides preliminary evidence for safety and effectiveness of Aripiprazole for COVID-19 delirium, but note that future trial data would be necessary to confirm this. We noted that several authors declared funding from Lundbeck and Otsuka (makers of Aripiprazole IM), so further caution is needed.
Publication date / reference: 13/08/20. Chen. Neurological involvement associated with COVID-19 infection in children. J Neurol Sci.
Summary: Correspondence in which the author reviewed studies reporting on multisystem inflammation syndrome in children (MIS-C). Of 187 children in these studies, 64 (34.2%) had neurological symptoms, most frequently headaches, positive meningeal signs (meningism), and/or altered mental status. From only eight LPs conducted, five children showed a non-specific pleocytosis. The author argues that the clinical and neurological characteristics of MIS-C patients suggest a post-infectious immune response.
Publication date / reference: 14/08/20. Anand et al. Myoclonus in patients with coronavirus disease 2019: a multicenter case series. Crit Care Med.
Summary: In this multi-centre case series across three tertiary care centres, Anand and colleagues presented the case of eight patients with PCR confirmed COVID-19 with clinical myoclonus. Clinical outcomes were variable; one patient died during the study period, five had no cognitive impairment or focal neurological deficits. In five patients, myoclonus resolved within two days of onset, whereas, in three patients it persisted for over 10 days. Seven patients experienced significant metabolic derangements, hypoxaemia or exposure to sedating meds that may have contributed to the development of myoclonus. One patient with encephalopathy developed prolonged myoclonus with no clear precipitating factor. Despite occurring across multiple centres, this study is limited by its small sample size.
Publication date / reference: 10/08/20. Restivo et al. Myasthenia Gravis Associated With SARS-CoV-2 Infection. Ann Intern Med.
Summary: Case series of three patients without previous neurologic or autoimmune disorders who were diagnosed with acetylcholine receptor antibody-positive myasthenia gravis after developing PCR-confirmed COVID-19. Each improved with steroids, IVIG, or plasmapheresis.
Publication date / reference: 10/08/20 Duong et al. Letter to the Editor: Neurohospitalist and COVID-19. Acta Neurol Belg.
Summary: Correspondence from neurohospitalists in Los Angeles describing a 50% decrease in neurological consultations and stroke alerts from April to June 2020, compared with the same time in 2019. The authors briefly describe the varied consultations of 88 patients with confirmed SARS-CoV-2 in their work. The predominant manifestation was altered mental state, but consultations occurred for stroke, isolated meningoencephalitis, fatal rhabdomyolysis, and potentially COVID-19 related Miller-Fisher Syndrome.
Publication date / reference: 12/08/20. Cunha et al. Movement disorders as a new neurological clinical picture in severe SARS-CoV-2 infection. Eur J Neurol.
Summary: Correspondence clinically characterising a claimed “new type of delayed onset movement disorder” in five patients who had been admitted to ICU for severe SARS-CoV-2 infection. On average abnormal movements developed three weeks after ICU discharge. Postural and action tremor was observed in four patients, with a mixed cortical-subcortical myoclonus in two. Most patients had cerebral microbleeds on MRI. DATSCAN was normal where conducted. Hypothesised mechanisms included direct CNS damage either by SARS-CoV-2 or by immune-mediated processes, or metabolic or post-hypoxic damage, or a combination.
Publication date / reference: 11/8/20. Agarwal et al. Neurological emergencies associated with COVID-19: stroke and beyond. Emerg Radiol.
Summary: In this case series, Agarwal and colleagues present five cases of neuroimaging findings in SARS-Cov-2 positive (PCR confirmed) patients presenting to their emergency department. The first case was of ischaemic stroke with large vessel occlusion which was thought to be secondary to dysregulation of the coagulation system and increased proinflammatory state in the setting of COVID-19 infection. The second case was of ischaemic stroke with embolic infarcts potentially secondary to a hypercoagulable state or an underlying cardiometabolic source. The third case was of acute tumefactive demyelination which was presumed to be secondary to SARS-Cov-2 infection given the monophasic appearance of the lesions in the setting of encephalopathy. The fourth case was of a cytotoxic lesion of the corpus callosum. The final case was of posterior reversible encephalopathy syndrome thought to be secondary to cytokine storm or metabolic derangement in acute liver failure.
Publication date / reference: 13/08/20. Case series of headache characteristics in COVID-19; Headache can be an isolated symptom. Headache.
Summary: The authors report a case series of 13 patients who were diagnosed with mild PCR-confirmed COVID-19 and having a chief complaint of headache. Their symptoms were questioned by a headache specialist, and symptoms and signs of viral meningo-encephalitis were absent. Headache was almost exclusively described as throbbing and/or pressing in nature, and aggravated with routine movements and bending over. Headache was holocranial with a particular focus in bilateral frontal and temporal areas. The authors concluded that headache could be an isolated symptom of COVID-19, which might possibly be ignored in asymptomatic patients.
Publication date / reference: 10/07/20. Fan et al. Neurological manifestations in critically ill patients with COVID-19: a retrospective study. Front Neurol.
Summary: The authors of this retrospective cohort study included 86 critically ill patients (defined as respiratory failure requiring mechanical ventilation, patients in shock, or patients complicated with other organ failure requiring ICU monitoring and treatment) with COVID-19. 65% of patients presented with at least one neurological complication, with 20/86 patients demonstrating symptoms involving the central nervous system, including delirium, cerebrovascular disease and hypoxic-ischaemic brain injury, whilst 6/86 patients displayed neuromuscular involvement and 7/86 experienced new stroke. Furthermore, patients with ischaemic stroke were significantly more likely to have antiphospholipid antibodies than those without stroke.
Publication date / reference: 21/07/20. Anand et al. Seizure as the presenting symptom of COVID-19: A retrospective case series. Epilepsy Behav.
Summary: This retrospective case series reported on seizures in COVID-19 patients, and particularly the associated clinical features, outcomes and risk factors. The study covered seven COVID-19 cases that presented to the neurological services at Boston Medical Centre with seizures admitted from April 2020 to May 2020. In all cases, seizures were the primary symptom of concern and a significant proportion had new onset seizures at presentation. A small majority (4/7; 57%) patients were discharged and returned to their baseline neurological function with no further seizures. Risk factors found in this group of patients included metabolic, systemic illness and viral effects.
Publication date / reference: 29/07/20. Needham et al. Mononeuritis multiplex: an unexpectedly common feature of severe COVID-19. MedRxiv (pre-print, not peer reviewed)
Summary: In this retrospective case series, Needham and colleagues reported the presence of focal neurological deficits in their post-COVID-19 follow-up clinic, for patients who had severe disease and required ICU. The focal deficits were related to axonal mononeuritis multiplex in 11/69 patients. Neuropathies were confirmed with neurophysiological studies establishing a heterogeneous pattern of nerve involvement. The authors considered that the neuropathies most likely occurred during the acute phase of COVID-19 illness, and that the active disease process was limited to this phase. However, the disease process is difficult to establish in this retrospective design and longitudinal prospective data is required to substantiate their hypothesis.
Publication date / reference: 29/07/20. Trigo et al. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. J Headache Pain.
Summary: In this single-centre retrospective cohort study, the authors examined all patients hospitalised with confirmed COVID-19 over a 5-week period (n=576) to study the association of headache with other clinico-demographic symptoms, and with mortality. Headache was present in 137 (23.7%) and was more likely to occur in women, and in conjunction with anosmia, myalgia, and fever. Headache was less likely in younger patients, those with lower disability on modified Rankin scale, and in the presence of increased inflammatory markers. Headache associated with reduced mortality in this sample. The authors speculate that patients with headache may have milder COVID-19, or that the presence of headache may represent an effective immune response. These results should be viewed with caution as the retrospective study included hospitalised patients only, so may have only presented those with headache in COVID-19 with more severe disease.
Publication date / reference: 30/7/20. Ora et al. Dyspnea perception and neurological symptoms in non-severe COVID-19 patients. Neurol Sci.
Summary: This structured interview study aimed to address whether there is a relationship between neurological symptoms and the perception (or lack thereof) of dyspnoea in COVID-19. Hypothesised mechanisms for lack of awareness of dyspnoea include damage to C-pulmonary fibres as a result of cytokine storm or direct neurotoxic effects of SARS-CoV-2. Structured interviews were performed in 22 non-severe patients divided into dyspnoeic and non-dyspnoeic patients. The prevalence of dyspnoea was low (31.8%) and contrary to the authors’ hypothesis, no relationship was found between dyspnoea and the presence of neurological symptoms. The prevalence of neurological symptoms was similar between groups and there was no difference in biological measures such as PaCO2 and lactate. The authors acknowledged the small sample size and thus the inability to draw conclusive results.
Publication date / reference: 16/07/20. Doo et al. Rare presentations of COVID-19: PRES-like leukoencephalopathy and carotid thrombosis. Clin Imaging.
Summary: In this retrospective report, Doo and colleagues described the unusual neurological findings in two patients with COVID-19. The first case was a 55-year-old man who presented with left wrist drop, which progressed to a left-sided hemiplegia. CT angiogram confirmed a large thrombus in the right common carotid artery and he was RT-PCR positive for SARS-COV-2 with no respiratory symptoms. The second case was a 64-year-old man with severe COVID-19 who developed rhythmic jerking movements after being weaned from sedation on ICU. Video EEG was consistent with status epilepticus and the patient required multiple antiepileptic drugs to halt the seizure activity. MRI brain found cerebral oedema and signs of a recent haemorrhage.
Publication date / reference: 11/07/20. Woo et al. Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients. J Neurol.
Summary: The authors reported two PCR-confirmed SARS-CoV-2 positive cases: a 44 year-old female with relapsing-remitting MS (Expanded Disability Status Scale score=2, very small disability in one function); and a 68 year-old female with neuromyelitis optica spectrum disorder (EDSS= 6.0, can walk 100m aided), both of whom were taking the B-cell depleting monoclonal antibody Rituximab. Their B-cell counts ranged from undetectable (former) to severely suppressed (latter). The two ladies had very different experiences: the former had a mild course and recovered quickly; the latter (older with multiple other comorbidities) had a rockier course, ventilated in ICU and complicated by bacterial superinfection, severe ARDS, tachyarrhythmia and prerenal failure, but also recovered completely. Authors argue that the two cases imply that immunological factors other than B cell-mediated antibody responses are required for COVID-19 control.
Publication date / reference: 08/06/20. Barzegar et al. Characteristics of COVID-19 disease in multiple sclerosis patients. Mult Scler Relat Disord.
Summary: This retrospective cohort study evaluated the characteristics and outcomes of potential COVID-19 disease in nine patients with MS, only two of whom were confirmed by RT-PCR. Seven of these patients were on disease modifying therapy. Most patients, including those on interferon beta or glatiramer acetate, reported a mild-course of illness. However, two patients treated with fingolimod and rituximab experienced severe illness. The findings of this study are limited by its selection approach and lack of confirmatory diagnosis.
Publication date / reference: 14/07/20. Loonstra et al. COVID-19 in multiple sclerosis: The Dutch experience. Mult Scler.
Summary: The authors characterise all reported patients with MS and clinically confirmed COVID-19 in the Netherlands, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology, up to 9th June (n=43). Twenty-two were hospitalised; more often male, older, and with secondary progressive disease / greater disability. In 36 patients with available data no association was observed between low lymphocyte count and requirement for hospitalisation. For instance three patients using fingolimod had a lymphocyte count of 0.3 X 109/L, and a mild course of disease. The findings should be interpreted with caution in this small and selected cohort, but there was no trend of a worse outcome in MS patients on disease-modifying therapies in general.
Publication date / reference: 14/07/20. Peeters et al. COVID-19 in people with multiple sclerosis: A global data sharing initiative. Mult Scler.
Summary: This innovative multi-centre collaboration sought to create a global data sharing platform to understand the determinants of COVID-19 severity in patients with MS. This preliminary report described the successful acquisition of data sharing processes and a consensus over what core data needs to be collected. This will be an interesting space to watch as the results of this project come to fruition.
Publication date / reference: 15/07/20. Porta-Etessam et al. Spectrum of Headaches Associated With SARS‐CoV‐2 Infection: Study of Healthcare Professionals. Headache.
Summary: This cross-sectional survey examined the characteristics and associated features of headaches in Spanish healthcare professionals who presented with headache during SARS-CoV-2 infection (n=112). Onset of headache was typically 3-4 days after onset of viral symptoms (mean=3.9, SD=6.0). The pain was most often holocranial (42.5%) and described as pressing (80.4%). Symptoms were exacerbated by head movement (46.4%) or physical activity (50.9%) in a proportion of cases. A history of headache was reported by 25.9% cases, with migraine the most common (17.9%).
Publication date / reference: 17/07/20. McCuddy et al. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series. MedRxiv pre-print (not peer-reviewed)
Summary: this is a retrospective case series of three patients with severe COVID-19 (PCR-confirmed) who developed ADEM. All three patients developed ARDS and required invasive ventilatory support. The neurological manifestations consisted of post-extubation encephalopathy in two patients and a severe diffuse weakness in the third patient. MRI showed bilateral, white matter hyperintensities and CSF analysis revealed elevated protein but normal cell count and negative SARS-CoV-2 PCR. The patients had a minimal response to iv corticosteroids and two of the patients treated with subsequent iv immunoglobulins showed no further improvement. The occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection required further attention.
Publication date / reference: 09/07/20. Parrotta et al. COVID-19 outcomes in MS: Observational study of early experience from NYU multiple sclerosis comprehensive care center. Neurol Neuroimmunol Neuroinflamm.
Summary: This retrospective cohort study reports on outcomes of COVID-19 in actively treated patients with MS or related disorders (n=76), of whom 65 were taking a disease modifying therapy. Hospitalisation frequency was consistent with that of the general population. As well as known risk factors for more severe viral illness (age and obesity), patients with progressive MS and those who required ambulatory assistance were more likely to die. Power was low and the authors acknowledged the risk of sampling and ascertainment bias, while calling for studies of how baseline inflammatory variables may influence viral susceptibility and course.
Publication date / reference: 04/07/20. Crescenzo et al. Frequency and Severity of COVID-19 in Multiple Sclerosis: A Short Single-Site Report From Northern Italy. Mult Scler Relat Disord.
Summary: Using a single-centre MS database survey with telephone follow-up, the authors report on the course of confirmed or probable COVID-19 infection in Italian MS patients (n=29), all of whom had been in remission for at least six months. All 29 survived; hospitalisation was required in only two cases. The relatively young age and low level of disability in the sample may have mitigated the course of illness. The authors called for future studies on larger cohorts to examine whether immunosuppressant disease-modifying treatments may modify the impact of COVID- 19.
Publication date / reference: 04/07/20. Luca et al. Seroconversion and Indolent Course of COVID-19 in Patients With Multiple Sclerosis Treated With Fingolimod and Teriflunomide. J Neurol Sci.
Summary: The authors describe two cases with relapsing-remitting MS, both in remission for at least one year. One was undergoing treatment with the immunomodulatory drug fingolimod, which was discontinued on confirmation of SARS-CoV-2 infection. She gradually recovered and at the time of write-up had not experienced a relapse in MS. The other patient was being treated with teriflunomide. This was also discontinued and the patient recovered. The IgG serum response to SARS-CoV-2 was limited in the patient treated with fingolimod and unremarkable in the patient treated with teriflunomide.
Publication date / reference. 10/07/20 (online ahead of print) Hubers et al. Management of patients with generalised myasthenia gravis and COVID-19: four case reports. J Neurol Neurosurg Psychiatry.
summary : The authors report four cases of patients with generalised Myasthenia Gravis (MG) that have been diagnosed with COVID-19. These patients showed no relevant worsening of MG symptoms. The severity of their COVID -19 disease course appeared to only be partly dependent on MG activity.
Publication date / reference: 29/06/20. Madia et al. Acute myopathic quadriplegia in COVID-19 patients in the Intensive Care Unit. Neurology.
Summary: Here the authors report on a series of 6 patients with acute myopathic quadriplegia on the background of severe COVID-19 infection. All patients had a flaccid quadriplegia. Neurophysiology demonstrated myopathic abnormalities (which improved in 5 of the patients). The authors argue that critical illness myopathy is the most likely explanation for the muscular deficit (due to the presence of relevant risk factors and relative sparing of facial and ocular muscle function).
Publication date / reference: 25/06/2020 Schupper et al. Neurological manifestations of pediatric multi-system inflammatory syndrome potentially associated with COVID-19. Childs Nerv Syst
Summary: Correspondence describing the cases of 2 children with major neurological complications. One 5 year old with positive COVID-19 antibodies and high IL6 level, presenting with fever, cough and abdominal pain, who was found to have R MCA infarct and diffuse contralateral subarachnoid hemorrhage with cerebral oedema after 5 days of ECMO. Brain death confirmed 3 days later. The second case was a 2 month-old boy with refractory respiratory failure placed on ECMO. This patient had high IL-6 level but negative COVID-19 antibodies. Day 1 post ECMO patient found to present with haemorrhage, CT later confirmed bilateral MCA and OCA infarct with haemorrhagic transformation. Authors note that ECMO is associated with high embolic stroke risk however they suggested the presentation of stroke earlier on in the treatment points to a different etiology.
Publication date / reference: 25/06/20. Pascual-Goñi et al. COVID-19-associated ophthalmoparesis and hypothalamic involvement. Neurol Neuroimmunol Neuroinflamm.
Summary: The authors describe two patients with COVID-19 who developed ophthalmoparesis and associated MRI findings (involving hypothalamus and mesencephalic tegmentum).
Publication date / reference: 17/06/20. Deiner et al. Ocular Signs of COVID-19 Suggested by Internet Search Term Patterns Worldwide. Ophthalmology.
Summary: The authors hypothesised that conjunctivitis could be a feature of COVID-19. They examined the 5-year daily search frequencies for ocular-related terms, using the Google ‘Timelines for Health’ application programming interface (API). They found a spike for 2020 in terms such as “sore eyes”, “burning eyes” and “conjunctivitis”. They call for ongoing clinical and epidemiological studies.
Summary: Case series of n=4 patients displaying abnormal mental status, deranged coagulation parameters, and markedly elevated D-dimer levels in association with COVID-19. Neuroimaging showed a common pattern of multifocal subcortical/cortical petechial-type hemorrhages, while SWI showed more extensive multifocal abnormalities. The authors propose a thrombotic microangiopathy may occur secondary to COVID-19.
Publication date / reference: 10/06/20 Singh et al. Headache as the Presenting Symptom in 2 Patients With COVID-19 and a History of Migraine: 2 Case Reports. Headache
Summary: Two case reports; one patient with episodic migraine and one with chronic migraine, who developed severe daily headache several days before symptoms of COVID-19. In both cases the headache preceding typical COVID-19 symptoms was distinct from the patients’ usual migraine, being more severe, more persistent, and more resistant to symptomatic treatment.
Publication date / reference: 10/06/20. Sotoca, et al. COVID-19 associated acute necrotizing myelitis. Neurol Neuroimmunol Neuroinflamm.
Summary: Case report of a 69-year-old woman presenting with PCR-positive Sars-CoV-2 and irradiated cervical pain, imbalance, left hand hypoesthesia, subtle left hand interosseous weakness, and general hyperreflexia. MRI spine showed T2 hyperintensities. IVMP helped initially but she deteriorated again. Repeat MRI showed progressive disease with central cord necrosis.
Publication date / reference: 09/06/20. Decavel et al. Tapia syndrome at the time of the COVID-19 pandemic: lower cranial neuropathy following prolonged intubation. Neurology.
Summary: Case report of a 62-year-old man with PCR-confirmed SARS-CoV-2 requiring intubation and frequent prone positioning, and who woke up with dysphonia, swallowing difficulties, and left hypoglossal nerve paralysis. A presumptive diagnosis of Tapia syndrome was made secondary to prolonged stretching of the lower cranial nerves.
Publication date / reference: 08/06/20. Noro et al. COVID-19 and benign intracranial hypertension: a case report. Rev Soc Bras Med Trop.
Summary: Case report of a 35 year-old woman with PCR-confirmed Sars-Cov-2, presenting with headache in association with fever and dyspnea. She became disorientated in hospital. MRI was suggestive for intracranial hypertension, CSF OP was 40cm H20, and CSF analysis was normal. She recovered well.
Publication date / reference: 02/06/20 Matos et al. COVID-19 Associated Central Nervous System Vasculopathy. Can J Neurol Sci.
Summary: 42-year-old patient who presented with altered mental status, slow movements and apathy one-week post detection of SARS-CoV-2 on NP swab. Examination revealed dysexecutive syndrome and perseveration. MRI confirmed multiple deep and subcortical lesions.
Publication date / reference: 02/06/20 Mirzaee et al. Focal Cerebral Arteriopathy in a COVID-19 Pediatric Patient. Radiology.
Summary: Case of a 12-year-old with focal cerebral arteriopathy and ischemic stroke. He presented with seizure, right hemiparesis, and dysarthria. SARS-CoV-2 was present in CSF and on nasopharyngeal swab.
Publication date / reference: 02/06/20 Fasano et al. COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy. Mov Disord.
Summary: In a cohort of non-advanced PD patients (n=105), COVID-19 risk and mortality did not differ from controls (n=92) but symptoms appeared milder. The authors believe a potentially protective role of vitamin D supplementation warrants future study.
Publication date / reference: 01/06/20 Giorgianni et al. Transient Acute-Onset Tetraparesis in a COVID-19 Patient. Spinal Cord.
Summary: Case of a 22-year-old female with SARS-CoV-2 who developed acute flaccid tetraparesis, hyperreflexia and complete incontinence. CSF did not detect SARS-CoV-2.
Publication date / reference: 31/05/20 Chaudry et al. COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection. MedRxiv (preprint)
Summary: Prospective study of 40 patients with SARS-CoV-2 and multiple sclerosis. Patients with more severe COVID-19 courses tended to be older, more likely to suffer from progressive staging, and had a higher degree of disability., Disease-modifying therapy use did not differ among courses.
Publication date / reference: 29/05/20 Manganelli et al. Brainstem involvement and respiratory failure in COVID-19]. Neurol Sci.
Summary: Case series (n=3) of patients with SARS-CoV-2 who were unable to be successfully extubated. Although the patients had recovered from their pneumonia, the authors propose a failure in central respiratory drive could stem from brainstem involvement.
Publication date / reference: 28/05/20 Nepal et al. An Unresponsive COVID-19 Patient. Emerg Radiol.
Summary: Case report of a 50-year-old male without comorbidity found unresponsive with COVID-19-related neurological complications. The patient had a normal CT head, however, MRI 7 days post admission revealed multiple white matter foci suggestive of acute infarcts of embolic origin or due to vasculitis.
Publication date / reference: 26/05/2020. Munz et al. Acute Transverse Myelitis After COVID-19 Pneumonia. J Neurol.
Summary: Case report of multifocal transverse myelitis following acute COVID-19 pneumonia
Publication date / reference: 25/05/20 Effects of COVID-19 on Parkinson’s Disease Clinical Features: A Community-Based Case-Control Study. Mov Disorders.
Summary: Motor and nonmotor of symptoms of PD significantly worsened in the COVID‐19 group when compared to controls.
Publication date / reference: 24/05/20 Carolina Andorinho de Freitas Ferreira et al. COVID‐19 and herpes zoster co‐infection presenting with trigeminal neuropathy. Eur J Neurol.
Summary: Case report of 39 year old male who developed reactivation of HZV which manifested as left trigeminal neuropathy. The patient also had SARS-CoV-2.
Publication date / reference: 24/05/2. Mukherjee et al. Ataxia as a presenting manifestation of COVID -19: Report of a single case. MedRxiv Preprint.
Summary: case report of a 53 year old individual with SARS-CoV-2 infection who presented with slurred speech and cerebellar ataxia and headache, two days before the onset of respiratory symptoms. He had a normal CT, however, could not undergo an LP or MRI brain due to clinical instability. He rapidly deteriorated and developed severe neck stiffness, with meningitis suspected.
Publication date / reference: 21/05/20 Franceschi et al. Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection. American Journal of Neuroradiology.
Summary: Report of two patients with lab confirmed SARS-CoV-2 who demonstrated PRES on their brain imaging. Both patients classically demonstrated wide fluctuations in blood pressure and altered mental state. The authors provide detailed analysis and demonstration of neuroimaging findings.
Publication date / reference: 21/05/20 Goh et al. Pearls and Oysters: Facial nerve palsy as a neurological manifestation of Covid-19 infection. Neurology.
Summary: 27-year-old male who on his 6th day of infection with confirmed SARS-CoV-2 developed signs consistent with left lower motor neuron facial palsy. CSF analysis was unremarkable, however, he demonstrated facial nerve enhancement on MRI.
Publication date / reference: 12/05/20 Salari et al. Incidence of Anxiety in Parkinson’s Disease during Coronavirus disease (COVID-19) pandemic. Movement Disorders.
Summary: Report demonstrates significantly raised levels of anxiety in sub-groups with PD vs aged matched controls. Further emphasizing the importance of this neuropsychiatric aspect of the condition.
Publication date / reference: 11/05/20 Anand et al. COVID‐19 in Patients with Myasthenia Gravis. Muscle and Nerve.
Summary: Case series of 5 patients with myasthenia gravis and SARS-CoV-2.
Publication date / reference: 08/05/20 Antonini et al. Outcome of Parkinson’s Disease patients affected by COVID‐19. Movement Disorders.
Summary: Report of outcomes of patients with Parkinson’s and SARS-CoV-2, authors suggest that PD patients of older age with longer disease duration are particularly susceptible to COVID-19.
Publication date / reference: 06/05/20 Delly et al. Myasthenic crisis in COVID-19. J Neurol Sci.
Summary: Single case report of myasthenic crisis in nasopharyngeal swab confirmed SARS-CoV-2.
Publication date / reference: 04/05/2020 Zanin L et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien).
Summary: Case report of a COVID-19 positive patient admitted for interstitial pneumonia and seizures. MRI showed newly diagnosed demyelinating lesions. High-dose steroid treatment allowed neurological and respiratory recovery. Authors speculate a delayed immune response induced by SARS-CoV-2.
Publication date / reference: 01/05/2020 Dinkin et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology.
Summary: Case series of two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis. One of the cases was diagnosed as presumed Miller-Fisher syndrome (ganglioside antibodies negative), and had partial response to IVIg treatment, the other had isolated ophthalmoplegia. CSF analysis is not mentioned in either case.
Publication date / reference: 30/04/2020 Sormani et al. An Italian programme for COVID-19 infection in multiple sclerosis. Lancet Neurol.
Summary: Retrospective multi-site study of 232 multiple sclerosis patients, 57 of whom tested positive for COVID-19 and 175 of whom had suspected COVID-19 symptoms The severity of COVID-19 infection in 232 patients was classified as mild in 96%, severe in 2% and critical in 3%. Of the six critical patients, five died.
Publication date / reference: 28/04/20 Kaya et al. Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report. J Neurol Sci.
Summary: Case report of a 38-year-old male with SARS-CoV-2 infection who developed acute confusional state and severely impaired visual acuity in ICU. Otherwise neurological examination was normal. Various T2 FLAIR hyperintensities were seen on MRI revealing vasogenic oedema similar to posterior reversible leucoencephalopathy (PRES).
Publication date / reference: 27/04/2020 Abdelnour L et al. COVID 19 infection presenting as motor peripheral neuropathy. J Formos Med Assoc.
Summary: Case report of a 69-year-old man who presented with bilateral lower limb weakness. Positive nasopharyngeal swab for covid-19. Authors unable to complete lumbar puncture or nerve conduction studies.
Publication date / reference: 21/04/2020 Zhang T, et al. COVID-19-Associated Acute Disseminated Encephalomyelitis – A Case Report. medRxiv (preprint)
Summary: Single case report of Acute Disseminated Encephalomyelitis (ADEM) in a COVID-19 patient.
Publication date / reference: 18/03/2020 Zhao, K. et al. Acute myelitis after SARS-CoV-2 infection: a case report. medRxiv (preprint).
Summary: Single case report of acute myelitis. The patient was admitted with acute flaccid paralysis of the bilateral lower limbs and urinary and bowel incontinence.
Mechanisms or biomarkers
Publication date / reference: 26/04/2021 Duarte-Neto et al., An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C. EClinicalMedicine.
Summary: This study examined autopsy findings in five paediatric COVID-19 cases to determine pathogenesis and immune-mediated mechanisms involved in COVID-19 infection in children. Tissue samples from all vital organs were obtained from children and adolescents who died from COVID-19 during the period between 18th March 2020 and 15th August 2020. Samples were analysed using various histological methods (RT-PCR, EM, IHC). The samples were obtained from five patients (one male and four female), from 7 months to 15 years of age. Two patients had severe underlying conditions (adrenal carcinoma and Edwards syndrome); whilst three other patients had no underlying conditions.
The three healthy patients presented with multisystem inflammatory syndrome (MIS-C) that manifested in myocarditis, colitis, as well as acute encelopathy with status epilepticus. Autopsy procedure identified SARS-CoV-2 particles in all patients in lungs, heart and kidneys. In two patients with MIS-C viral particles were also detected in endothelial cells from heart and brain. Furthermore, SARS-CoV-2 was detected in the brain tissue of a paediatric patient with MIS-C with acute encelopathy, and in the intestinal tissue of a paediatric patient with acute colitis. Autopsy findings differed from patient to patient and included: mild to severe COVID-19 pneumonia; pulmonary micro thrombosis; cerebral oedema with reactive gliosis; myocarditis; intestinal inflammation; haemophagocytosis. This research demonstrates the two major patterns of COVID-19 in paediatric patients: 1) a pulmonary disease with severe acute respiratory disease and diffuse alveolar damage; or 2) multisystem inflammatory syndrome affecting various organs. Thus, it can be concluded that SARS-CoV-2 causes cellular ultrastructural changes, which has a direct impact on tissues involved in the pathogenesis of MIS-C.
Publication date / reference: 16/04/21. Wallukat et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent post-COVID-19 symptoms. J Transl Autoimmun.
Summary: The authors examined the presence of active antibodies to G-protein coupled receptors (GPCR-AAB) in 31 covid-survivors of whom 29 suffered chronic neurological sequelae. The spectrum of neurological syndromes included fatigue, attention-deficit disorder, taste/smell dysfunction, tremor and dysautonomia. Between two to seven antibody types to neuroactive and vasoactive receptors were identified in all subjects, including two patients with no chronic symptoms. The authors conclude that GPCR-AAB may play a role in long COVID-19; however, this statement would be strengthened by inclusion of control subjects and association of different antibody types with specific neurological syndromes.
Publication date / reference: 01/04/2021 Frithiof et al. Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study. Clin Neurophysiol.
Summary: This cohort study aimed to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in COVID-19 patients with intensive care unit acquired weakness (ICUAW). The authors included (n=111) COVID-19 patients and found 11 developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group and correlated with nerve amplitudes. They concluded that CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.
Publication date / reference: 23/03/2021 Yapici-Eser et al., Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins’ Mimicry of Human Protein Interactions Front Hum Neurosci
Summary: In this study, by using a computational methodology, authors aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins. 11 of the 29 SARS-CoV-2 proteins’ structures were extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the “interface mimicry”.
Publication date / reference: 9/4/2021. Casagrande et al. Detection of SARS-CoV-2 genomic and subgenomic RNA in retina and optic nerve of patients with COVID-19. Br J Ophthalmol.
Summary: Casagrande and colleagues analysed the retina and optic nerves from 14 eyes of 14 deceased patients who had confirmed SARS-Cov-2 infection. In SARS-Cov-2 subgenomic (sg) RNA was detected in 7 retinal biopsies and 10/13 optic nerve biopsies. Whilst this may indicate neurotropism, failure to isolate the virus and negative SARS-Cov-2 immunohistochemistry indicates the absence of active infection.
Publication date / reference: 16/03/2021 Arunachalam et al. SARS-CoV-2: The road less travelled – from the respiratory mucosa to the brain. ACS Omega.
Summary: This animal model study was conducted to investigate the theoretical pathway of SARS-CoV-2 to the CNS. Mice were injected with 50μg of ICG directly into respiratory mucosa in the maxillary sinus region, or nasal inhalation. The mice were then scanned at regular intervals in vivo to track the migratory fluorescent trace from ICG. The authors detected more intense brain flurescence following direct injection than nasal route. The authors hypothesise that nasal muscosa hasa barroer function preventing dye entry into the circulation. However, the exact route taken by the SARS-CoV-2 virus to the brain was not elucidated by this study.
Publication date / reference: 12/03/2021. Donegani et al. Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection. Biomedicines.
Summary: The authors of this neuroimaging study aimed to explore the brain metabolic correlates of persistent olfactory dysfunction in patients who recovered from the acute phase of COVID-19. They conducted whole-body [18F]-FDG PET in 22 patients, over half of whom had persistent olfactory dysfunction. Voxel-wise analysis was used to ascertain a relative hypometabolism in bilateral parahippocampal and fusiform gyri and in left insula in patients with smell disturbance in comparison to those without. The authors hypothesised that cortical hypometabolism could underlie persistent olfactory disturbance in COVID-19.
Publication date / reference: 08/03/2021 Danoun et al. Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19. Epilepsy Behav.
Summary: In this retrospective study of hospitalised patients, the authors looked to characterise the EEG correlates of severe COVID-19. Of 110 patients who had EEGs taken, 22% had EEG evidence of new-onset seizures (7% with status epilepticus). After adjusting for COVID-19 severity, EEG markers were not predictive of outcome (including death).
Publication date / reference: 21/03/2021 Cunningham et al. Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms. J Infect Dis.
Summary: In this prospective mechanistic study, sixteen patients with neurological manifestations of covid-19 had serum and CSF samples taken. As we have seen in the vast majority of studies, none of the CSF samples were positive for SARS-CoV-2 (via PCR). Despite this, IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF.
Summary: This prospective study characterised EEG patterns of patients with critical COVID-19 with suspected encephalopathy to correlate findings to clinical outcomes. EEGs on 33 patients were conducted after removal of sedation, with SEPs and BAEPs conducted if EEGs were unreactive. Clinical outcomes were assessed after 7 and 14 days. Clinical outcomes at day 14 were associated with unreactive background activity, the presence of delta waves and low-voltage activity. Multimodal evoked potentials demonstrated it is likely somatosensory and auditory functions of the central nervous system were preserved. They conclude EEG patterns demonstrate encephalopathy within the study population and may predict clinical outcomes.
Publication date / reference: 04/03/21. Garcia et al. Interleukin 6 and depression in patients affected by COVID-19. Med Clin (Engl Ed).
Summary: In n=27 COVID-19 patients the authors found no correlation between the levels of IL-6, IL-1β, and TNF-α with Geriatric Depression Scale scores.
Publication date / reference: 4/03/2021 García et al. Interleukin 6 and depression in patients affected by Covid-19. Med Clin (Engl Ed).
Summary: This observational study aimed to assess correlation between IL-6, IL-1β and TNF-α and depressive symptoms. The authors included (n=27) patients admitted for Covid-19 older than 60 years with an interleukin determination. They did not find correlation between IL-6 levels and the geriatric depression scale (GDS) score; with IL-1β levels nor of TNF-α. 11.1% presented score compatible with depressive disorder. It was associated with a deficiency of Noradrenaline and Serotonin. They concluded that they found no correlation between the levels of IL-6, IL-1β, and TNF-α with the GDS score.
Publication date / reference: 11/03/2021 Lin et al. EEG Abnormalities are Common in COVID-19 and are Associated with Outcomes. Ann Neurol.
Summary: The multi-center retrospective cohort study aimed to determine the prevalence and risk factors for electrographic seizures and other EEG patterns in patients with COVID-19 undergoing clinically indicated continuous electroencephalogram monitoring (cEEG), and to assess whether EEG findings are associated with outcomes. The authors identified (n=197) patients with COVID-19 referred for cEEG at 9 participating centers and found that Electrographic seizures were detected in 9.6%, including nonconvulsive status epilepticus (NCSE) in 5.6%. Epileptiform abnormalities (either ictal or interictal) were present in 48.7%. Preceding clinical seizures during hospitalization were associated with both electrographic seizures (OR= 6.51) and NCSE (OR=8.34). A preexisting intracranial lesion on neuroimaging was associated with NCSE (OR=4.33). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (HR= 4.07). In competing risks analysis, hospital length-of-stay increased in the presence of NCSE. They concluded that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically-indicated cEEG, and are associated with adverse clinical outcomes.
Publication date / reference: 24/02/2021 Torices et al. Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection. Res Sq.
Summary: This study aimed to analyse the expression pattern of SARS-CoV-2 receptors in naïve and HIV-1-infected cells to try and find a possible pathway of the virus entry into the brain and the effect HIV-1 has in this process, especially in the Neurovascular Units (NVU), which form the blood-brain barrier, that are proposed to be involved in the entry. They assessed gene and protein expression profiles and examined if brain endothelial cells can be affected by the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors (S1 subunit of S protein). They found that receptors involved are coexpressed in the cells of the NVU, especially in astrocytes and microglial cells.They found them to be active and the S1 subunit changes the expression of proteins. In addition, HIV-1 infection upregulated gene expression in brain astrocytes and microglia cells.
Publication date / reference:04/2021 Mennunci et al. Co-expression of the SARS-CoV-2 entry receptors ACE2 and TMPRSS2 in healthy human conjunctiva. Exp Eye Res.
Summary: The authors of this study analysed the surgical specimens from of 11 patients who underwent retinal detachment surgery to establish the expression of ACE2 and TMPRSS2, the entry receptors for SARS-CoV-2 in human conjunctival tissue, using Western blot and confocal microscopy. The results showed that both ACE2 and TMPRSS2 were expressed and co-localised in all samples. In a semi-quantitative analysis TMPRSS2 was similarly expressed in all samples, while the expression of ACE2 was more variable.
Publication date / reference: 13/02/2021 Sun et al. Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations Cells
Summary: In this study, plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6. Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls.
Publication date / reference: 25/02/21. Qin et al. Long-term micro-structure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations. J Clin Invest.
Summary: Writing in the Journal of Clinical Investigation, Qin et al studied several brain MRI outcomes at the three-month follow-up point in COVID-19 patients who had shown no specific neurological manifestations at the acute stage. The authors compared 19 patients who had recovered from mild COVID-19, and 32 patients who had recovered from severe (but non-ITU) COVID-19, with 31 age-, sex-, and education-matched healthy controls. Despite having no recorded neurological complications of acute illness, survivors of severe illness had reduced cortical thickness and subcortical volumes in multiple left hemispheric brain areas including the left insula, hippocampus, superior temporal gyrus, putamen, and thalamus, in comparison to controls. Modelling further suggested reductions in cerebral blood flow across cortical gray matter, particularly in the left insula, while tractography revealed altered white matter microstructure in multiple frontolimbic tracts. Brain microstructure changes and the CBF decrease correlated with the level of inflammatory markers, although the timing of the measurement of inflammation in relation to the scanning was not immediately clear. In general, patients with milder COVID-19 had more attenuated abnormalities. As with much similar research the sample is small and selected, and partly based on retrospective review of clinical notes. However the gradient with COVID-19 severity is biologically plausible, and of note given that the enrolled patients ostensibly had no acute neurological insults. The authors call for monitoring of gray matter atrophy, CBF, and white matter microstructure in patients recovering from COVID-19.
Publication date / reference: 20/02/2021.Singh et al. Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs. Brain Behav Immun.
Summary: This preclinical study, the investigator reported experiments done in mice. Artificial strokes were induced in Mice, tituses of brain, lung, heart and kidney tissues of these mice were analysed 1 and 3 days after the stroke. An increased level of ACE2 was found in the lung tissue of stroke mice compared to non stroke mice. The authors postulated that patients with brain injuries may have increased binding affinity to SARS-CoV-2 in their lungs which might explain why stroke is a risk factor for higher susceptibility to develop COVID-19.
Summary: In this preclinical study Tiwari et al. report the reduction of SARS-CoV-2 infection through spike protein and TMPRSS2 inhibitors, using human stem cell derived lung organoids (LORGs), cerebral organoids (NPCs), neurons and astrocytes.
Publication date / reference: 29/02/2021 Blanco-Palmero et al. Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms. J Neurol.
Summary: The authors of this study assessed serum alpha-synuclein in seven COVID-19 patients with myoclonus, Parkinsonism and/or encephalopathy, thirteen age and sex matched COVID-19 patients without neurological involvement and either age and sex matched healthy controls. No significant difference was observed.
Publication date / reference: 10/01/2021 Garcia et al. Cerebrospinal fluid in COVID-19 neurological complications: no cytokine storm or neuroinflammation. (MedRxiv. Not peer reviewed)
Summary: The authors of this cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 patients with neurological complications (stroke, encephalopathy and headache) was compared with CSF from 82 healthy, infectious and neuroinflammatory and stroke controls. CSF from COVID-19 patients showed little neuroinflammatory changes, and displayed anti-SARS-CoV2 antibodies in 77% despite absence of SARS-CoV2 RNA.
Publication date / reference: 19/02/2021. Nicolas Hoertel et al. Observational study of haloperidol in hospitalized patients with COVID-19. PLoS One.
Summary: This is a multicentre observational study investigating the use of haloperidol in association with risk of intubation and death in patients with COVID-19. Of 15121 patients who were admitted and tested positive with COVID-19, 39 patients received haloperidol. This study found no significant association between haloperidol use and intubation, death, and early discharge.
Publication date / reference: 20/01/2021. Chen et al. The Spatial and Cell-type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains. Front Neurol.
Summary: Primary research investigating distribution of ACE2 receptors in the human and mouse brain using freely accessible genom data from three brain transcriptome databases . Author found ACE2 receptors were relatively highly expressed in the choroid plexus and paraventricular nuclei of thalamus. Nuclear expresses were found in both neural and non-neuronal cells. Distribution in the mouse model was similar. From the finding the authors postulate that direct invasion of SARS-CoV2 may be capable of direct infection of the nervous system causing neurological symptoms. It is worth bearing in mind however, despite theoretical possibilities, clinical evidence of direct CNS invasion from SARS-CoV2 has so far been lacking.
Publication date / reference: 21/01/2021. Varma et al. Novel Targets of SARS-CoV-2 Spike Protein in Human Fetal Brain Development Suggest Early Pregnancy Vulnerability. Front Neurosci.
Summary: Primary research where expression of known SARS-CoV2 spike protein interactors were analysed using RNA sequencing in available fetal brain bulk. Notably the authors found FURIN, ZDHHC5, GOLGA7, and ATP1A1 to be highly expressed in the fetal brain, the latter three are noval S-protein interactors. The found interactor expressions peaks between 12-26week post conception, and the authors postulated their abundant expression in the fetal brain could play a direct/indirect role in SARS-CoV 2 pathogenesis, in particular suggesting an increased vulnerability to COVID-19 for during the 2nd and 3rd trimester of pregnancy.
Publication date/reference: 18/01/2021 Lou et al., Neuropathology of COVID-19 (neuro-COVID): clinicopathological update. Free Neuropathol.
Summary: This was a retrospective case series (n=184), focusing on neuropathological findings present in COVID-19 patients. The authors discuss the virology of COVID-19 focusing on the entry mechanism of SARS-CoV-2 into human cells. The limitations of COVID-19 laboratory testing are detailed. The main focus of the work is on the neuropathological findings and neuropathogenesis of COVID-19, including detailed histopathological reporting of COVID-19 in neural tissue.
Publication date / reference: 02/2021. Quincozes-Santos et al. COVID-19 impacts the expression of molecular markers associated with neuropsychiatric disorders. Brain Behav Immun Health.
Summary: Quincozes-Santos and colleagues analysed data extracted from clinical samples of patients with SARS-Cov-2 infection regarding differential gene expression. From this analysis, they identified 171 genes which were found to have a causal relationship with neuropsychiatric disorders including schizophrenia, autism, depression and alcohol dependence. The authors propose that the neuropsychiatric symptoms of patients with these conditions may be exacerbated by COVID-19 infection.
Publication date / reference: Feb 2021. Quincozes-Santos et al. COVID-19 impacts the expression of molecular markers associated with neuropsychiatric disorders. Brain Behav Immun Health.
Summary: The authors asked whether any genes were differentially expressed in clinical samples from patients with COVID-19. They curated published lists of differentially expressed genes from three earlier studies and intersected the resulting list with genes associated with neuropsychiatric disorders. They found a number of genes expressed in COVID-19 samples which were associated with neuropsychiatric disorders. Although it is an interesting idea the essential problem with their approach seemed to be that the differential comparators in the source studies were not controlled – and in some cases, not clearly stated – making it hard to draw meaningful conclusions from their big list. And on the question as to why we should expect genes expressed in bronchial epithelium (for instance) to have relevance to psychiatry, the authors are silent.
Publication date / reference: 22/01/21. Klingenstein et al. Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb. Cells Tissues Organs.
Summary: The authors of this mechanistic study evaluated the expression of ACE2 and TMPRSS2 proteins – both of which mediate SARS-CoV-2 fusion with host cells – across human postmortem nasal and olfactory tissue. ACE2 was detected in the olfactory and respiratory epithelium of the nasal septum, conchae and the paranasal sinuses. However, ACE2 was not detected in olfactory receptor neurons in the olfactory epithelium but was present in the olfactory bulb. TMPRSS2 was detected in the olfactory epithelium. The authors suggested that this provides evidence that SARS-CoV-2 enters cells of the upper respiratory tracts via ACE2 and TMPRSS2 and that this may underlie altered smell and taste in COVID-19.
Publication date / reference: 7/12/20. Cui et al. Clinical characteristics and immune responses of 137 deceased patients with COVID-19: a retrospective study. Front Cell Infect Microbiol.
Summary: This retrospective case-control study of hospitalised COVID-19 patients (n=836) aimed to identify the clinical and immune correlates of mortality from the disease. Characteristics were compared between the survivor (n=699) and deceased (n=137) patient groups using odds ratios. The authors identified many significant correlates including, eGFR <90 ml/min/1.73; OR 3.859 (1.549-9.617) p<.001, CRP ≥ 25 mg/L; OR 4.391 (1.021-18.883) p<.05 and procalcitonin ≥ 0.05 ng/ml; OR 4.391 (1.021-18.883) p<.001. This study identified factors that could be used clinically to predict mortality and poor prognosis with COVID-19.
Publication date / reference: 28/12/20. Virhammar et al. Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity. Eur J Neurol.
Summary: This was a prospective cohort study of COVID-19 patients (n=19) with neurological symptoms. CSF was analysed for biomarkers via lumbar puncture. Levels of NfL protein correlated significantly with the number of days spent in ICU (p<.001) and was correlated with COVID-19 severity (r =.56, p <.05). The authors concluded that CSF levels of NfL protein specifically were associated with neurological disease in COVID-19 and could thus be a novel biomarker.
Publication date / reference: 30/12/2020 Sutter et al. Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019. Ann Neurol.
Summary: This cross-sectional study presents a comparison of the concentrations of Serum neurofilament light chain (sNfL) as a specific biomarker of neuronal injury in 29 critically ill patients with COVID-19, 10 critically ill non-COVID-19 patients and 259 healthy controls. sNfL levels were on average 2.6 times higher in COVID-19 patients compared with non-COVID-19 patients (regression coefficient β = 2.58 [1.23–5.42], p = 0.014; age: βper year = 1.03 [1.01–1.05], p = 0.010); COVID-19 patients also had 5.7 times higher median sNfL levels than healthy controls.
Publication date / reference: 31/12/2020. Correlation between CSF biomarkers and COVID-19 meningoencephalitis: A case series Resp Med Case Reports.
Summary: This study aimed to shed light on the CSF pattern and clinical characteristics of meningoencephalitis in COVID-19 patients in Zanjan, Iran. The authors included patients with COVID-19-confirmed infection who had neurological symptoms, followed by a diagnostic lumbar puncture (LP) and if leukocytes were present in CSF, viral and bacterial causes were evaluated. Authors found that the most common clinical symptom of patients was a decrease in level of consciousness. Although authors did not have any cases of positive RT-PCR for COVID-19 in lumbar puncture specimens, the justification of neurological symptoms in patients can be due to transient presence of the virus in the CSF, and inflammation or autoimmune response caused by the virus.
Publication date / reference: 12/01/2021 Eric Song et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain J Exp Med.
Summary: In this study, the authors used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, they observed infection evidence accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. They demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, the authors demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, they detect SARS-CoV-2 in cortical neurons.
Publication date / reference: 12/01/2021. Michael Heming et al. Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid. Immunity.
Summary: This study used single cell sequencing to examine the immune cell profiles from CSF of Neuro-COVID patients in order to further understand the aetiology of neurological manifestations of COVID-19.
Publication date / reference: 02/12/2020 Yu et al., Complications and Pathophysiology of COVID-19 in the Nervous System. Front Neurol
Summary: The authors review complications and nervous system associations of COVID-19. Regarding nervous system complications they discuss direct invasion and: Viral Meningitis/Encephalitis, Encephalopathy, Acute Disseminated Encephalomyelitis, Cerebrovascular disease and epilepsy. They also discuss direct invasion causing PNS symptoms such as Hyposmia and Hypogeusia. They also mention post-infection links with immune dysfunction. They suggest the neurological spectrum seen in COVID-19 patients can offer clues to severity, and that neurologists may consider neurological long-term effects.
Publication date / reference: 26/11/2020 Besnard et al. Electroencephalographic Abnormalities in SARS-CoV-2 Patients. Front Neurol.
Summary: In this single-site retrospective analysis (n = 42) the authors found that confusion and seizures were the most common indications for EEG requests in COVID-19 inpatients, whose condition ranged from mild to severe. The EEG findings for the range of included neuropsychiatric conditions were generally non-specific, with 9/42 patients showing EEG signs of encephalopathy. The authors were not clear about the relevance of their findings above and beyond assisting in diagnosis.
Publication date / reference: 09/12/20. Toklu et al. Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status. Int J Emerg Med.
Summary: An observational retrospective cohort to assess the CSF findings of COVID 19 patients showing a mild increase in protein in the CSF of the COVID-19 patients. Elevated Neuron Specific Enolase (NSE) is proposed to have diagnostic/prognostic value as a biomarker in CSF for COVID-19 patients who have altered mental status.
Publication date / reference: 09/12/2020 Toklu et al., Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status. Int J Emerg Med
Summary: This retrospective multi-centre study (20) aimed to investigate CSF findings in confirmed COVID-19 patients (n=79). 24% of these patients presented with neurological symptoms including: dizziness, vomiting, aphasia, altered mental status or encephalopathy. 25% of patients had hypernatremia. Key CSF findings were: 63% of these patients had elevated protein, 1% had significantly elevated neuron-specific enolase (NSE) level. The authors suggest that these results could begin to give further clues in terms of outcome in COVID-19 patients with neurological symptoms.
Publication date / reference: 25/11/2020 Fodoulian et al. SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience
Summary: In their study on potential targets for SARS-CoV-19 viral invasion, Fodoulian et al. generated RNA-seq libraries from human olfactory neuroepithelia and demonstrated that a subset of sustentacular cells in the olfactory neuroepithelium expresses ACE2, responsible for the binding of SARS-CoV-2, and coexpresses TMPRSS2, which facilitates viral entry. An exploration of potential expression of ACE2 and TMPRSS2 of brain cell types in both mice and humans demonstrated that ACE2 was also expressed in various non-neuronal and neuronal types (Purkinje cells, astrocytes, oligodendrocytes) some of which also coexpressed TMPRSS2.
Publication date / reference: 14/11/20. Abrishami et al. Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: A case-control study. Can J Ophthalmol.
Summary: The authors aimed to quantify the density of foveal capillary plexi and the area of the foveal avascular zone (FAZ) in n=31 recovered COVID-19 patients using optical coherence tomography angiography. Compared to 23 healthy controls, vascular density was significantly lower in the COVID-19 patients, with no significant difference in the area of the FAZ. The authors conclude that the causes of the retinal capillary alterations detected in this study are unclear, and call for more research.
Publication date / reference: 13/10/20 Magro et al. Severe COVID-19: A multifaceted viral vasculopathy syndrome. Ann Diagn Pathol.
Summary: The authors of this study conducted pathology assessment on tissue samples from 12 individuals who had died from COVID-19. Key findings included the following: high copy infectious virus was mostly limited to the alveolar macrophages and endothelial cells of the septal capillaries, viral spike protein without viral RNA localised to ACE2+ endothelial cells in microvessels that were most abundant in subcutaneous fat and brain, only endocytosed pseudovirions induced marked up-regulation of IL6, TNF alpha, and other COVID-19 associated proteins. The authors conclude that the two distinct mechanisms of serious COVID-19 infection are: microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and the pseudovirions docking on ACE2+ endothelial cells most prevalent in skin/subcutaneous fat and brain that activates the complement cascade resulting in systemic procoagulant state as well as cytokine storm.
Publication date / reference: 30/11/20 Meinhardt et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19
Summary: This neuropathological case series aimed to establish whether SARS-CoV-2 RNA and protein are present in the nasopharynx and several brain regions. The authors conducted autopsies on unselected deceased individuals who had either had a positive SARS-CoV-2 PCR test (n=31) or clinical features highly suggestive of COVID-19 (n=2), examining the olfactory mucosa, olfactory bulb, olfactory tubercle, oral mucosa, trigeminal ganglion, medulla oblongata and cerebellum. SARS-CoV-2 RNA was most commonly found in the olfactory mucosa (n=20 out of 30) but a minority had SARS-CoV-2 RNA in the medulla or cerebellum. They also found SARS-CoV S protein in areas that were positive for SARS-CoV-2 RNA. They conclude that SARS-CoV-2 can invade the CNS via the transmucosal route. Post-mortem studies have the inherent bias of focussing on the most unwell individuals, often several days after their death, which can compromise the interpretation of specimens. There was no group of control patients, but the authors did examine for the presence of SARS-CoV-2 RNA in the carotid artery as a control tissue, finding evidence for the virus in n=1 out of 13. It is certainly an interesting contribution to the discussion about the neuroinvasive potential of SARS-CoV-2.
Publication date / reference: 13/11/2020. Yu et al. Innate and adaptive immunity of murine neural stem cell-derived piRNA exosomes/microvesicles against pseudotyped SARS-CoV-2 and HIV-based lentivirus. iScience.
Summary: the investigate the brain’s immune defences the authors tested exosomes/microvesicles (Ex/Mv) isolated from murine hypothalamic neural stem/progenitor cells (NSCs) for activity against RNA viruses. They found that these vesicles have both innate and possibly adaptive functions in the neural immune response, postulating that these NSCs could be used to combat viruses including SARS-CoV-2.
Publication date / reference: 09/11/20. Kaneko et al. Flow-Mediated Susceptibility and Molecular Response of Cerebral Endothelia to SARS-CoV-2 Infection. Stroke.
Summary: The authors compared “expression of ACE2 and TMPRSS2 in children and adolescent (age 5-19) brain microvascular cells with that of human umbilical vein endothelial cells (HUVECs), under conditions of shear stress in a 3D-printed model of the human middle cerebral artery (MCA)”. They “created a series of 3D vessel models of varying diameter (2–4 mm), endothelialized the luminal surface with HUVECs or human brain microvascular endothelial cells, and subjected these” to various experiments. They showed primarily that normal ACE2 gene expression by endothelial cells in the human brain is low, and identified a unique gene expression profile within brain endothelial cells in response to spike protein binding.
Publication date / reference: 15/10/2020 Cabañes-Martínez et al. Neuromuscular involvement in COVID-19 critically ill patients. Clin Neurophys.
Summary: In this study, the authors examined the neuropathologcial findings of covid-19 patients with clinically suspected ICU-related myopathy or neuropathy. In toal, 4/12 patients presented with signs of a sensory-motor axonal polyneuropathy on nerve conduction studies.The authors noted that in all patients there were no pathological findings specific to SARS-CoV-2.
Summary: In this interesting, yet tantalisingly short, paper, Younger details some aspects of cerebral post-mortem examination of fifty patients with severe covid-19. In total, 25 had hypoxic ischaemic changes, eight had encephalitis, and two showed acute disseminated encephalomyelitis (ADEM)-like changes. There were additional markers of inflammation, such as microscopic infarcts, leptomeningeal inflammation, and T-cell infiltration in some of the tissue.
Publication date / reference: 11/10/2020 Buzhdygan et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis.
Summary: This interesting study used post-mortem brain tissue that angiotensin converting enzyme 2 (ACE2) is expressed throughout vessels in the frontal cortex and are upregulated in dementia and hypertension. They also showed that SARS-CoV-2 spike proteins alter the blood brain barrier and trigger pro-inflammatory responses on brain endothelial cells.
Publication date / reference: 02/10/20. Cooper et al. Quantification of neurological blood-based biomarkers in critically ill patients with coronavirus disease 2019. Crit Care Explor.
Summary: In this multicenter prospective observational study, 27 COVID-19 ICU patients were compared with 19 ICU controls. COVID-19 patients were seen to have significantly high glial fibrillary acidic protein compared to ICU controls with pneumonia of other aetiology. In addition, in COVID-19 patients it was observed that glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase L1 and neurofilament-light chain positively correlated with Intensive Care Delirium Screening Checklist score and were increased in patients with delirium (Intensive Care Delirium Screening Checklist >4 in the COVID-19 group but not in controls.
Publication date / reference: 08/10/2020 Chen et al. A Retrospective Analysis of the Coagulation Dysfunction in COVID-19 Patients. Clin Appl Thromb Hemost.
Summary: Retrospective review of coagulation dysfunction in mild versus severe COVID-19 groups. As expected, markers of coagulopathy (PT, thrombin time, and D-dimer) were raised in the severe group. The authors suggest that raised D-dimer has a reasonable sensitivity and specificity for stratifying severe cases, but caution may be warranted since D-dimer is a non-specific marker.
Publication date / reference: Oct 2020. Quisi et al. The CHA2DS2-VASc score and in-hospital mortality in patients with COVID-19: A multicenter retrospective cohort study. Turk Kardiyol Dern Ars.
Summary: This multicentre retrospective study included a total of 349 patients with COVID-19. The CHA2DS2-VASc score was significantly higher in non-survivor COVID-19 patients than in survivor COVID-19 patients, and predicted in-hospital mortality in patients with COVID-19, regardless of the presence or absence of atrial fibrillation.
Publication date / reference: Sept 2020 Nikbakht et al., How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms. Mult Scler Relat Disord
Summary: This paper proposes mechanisms looking at how it can cause epilepsy and seizures. It speculates that the destructive effects of Covid-19 in the central nervous system could be caused by a cytokine storm produced by either the entry of pro-inflammatory cytokines from the periphery into the CNS, or by the production of these cytokines by activated microglia. Secondary seizures may be initiated after strokes, electrolyte imbalance, increased oxidative stress, and mitochondrial dysfunction in Covid-19 patients.
Publication date / reference: 06/10/20. Sonkaya et al. Cerebral hemodynamic alterations in patients with Covid-19. Turk J Med Sci.
Summary: Case-control study (20 COVID-19 patients and 20 healthy controls) comparing MCA transcranial doppler imaging between the two groups. Unfortunately the results are not clearly stated for the non-expert reader making it hard to be sure (for this reviewer) of the core finding.
Publication date / reference: 01/10/2020. Edén et al. CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series. Neurology.
Eden at al present a case series of 6 patients with COVID-19 and neurological symptoms (encephalopathy, dysgeusia and meningism). They assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]). They found that SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0–37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patient. However, this was not detected in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. CSF NfL was elevated in 2 patients. In terms of markers of CNS infection, median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all. While the authors set out to test a hypothesis centered on CNS SARS-CoV-2 invasion, they could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. Conversely, they suggest that neuropathogenesis in COVID-19 is likely multifactorial, driven by hypoxemia, hypercoagulability and systemic inflammation, especially in severe clinical manifestations of COVID-19. However, the authors acknowledge that the validity of the findings are limited by the small sample size and the inclusion of moderate-severe cases of COVID-19.
Publication date / reference: 08/09/20. Yi et al. Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus. Viruses.
Publication date / reference: 02/09/20. Ramani et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J.Summary: In a preclinical study the authors show that SARS-CoV-2, isolated from a German patient, can enter 3D human brain organoids within two days of exposure, and preferably targets neurons in this model system. Cleverly, faced with the problem of having no specific commercial antibody to SARS-CoV-2, the authors used serum from recovering human patients to develop their own. Imaging of the neurons of organoids suggested that SARS-CoV-2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. The data contribute to the debate over the potential neurotoxic effect of SARS-CoV-2 and suggest that brain organoids could be one way to model certain aspects of the neurological effects of COVID-19. The authors acknowledge that their study provides only initial insights in primitive brain-like tissues. Further experiments may dissect viral replication mechanisms and whether there are ACE2 independent pathways for viral entry.
Publication date / reference: 26/08/20. Deigendesch et al. Correlates of critical illness-related encephalopathy predominate postmortem COVID-19 neuropathology. Acta Neuopathol.
Summary: The authors reported neuropathological findings for seven confirmed COVID-19 patients, compared with a SARS-CoV-2 negative control autopsy cohort of individuals with non-septic and systemic inflammatory/septic clinical courses. They found evidence of systemic inflammation with greater microglial activation in the brainstem of COVID-19 patients compared to non-septic controls. They concluded that microglial activation represents critical illness-related encephalopathy, and not a disease-specific finding. Their interesting paper is limited by the very small sample size.
Publication date / reference: 25/08/20. Lukiw et al. SARS-CoV-2 infectivity and neurological targets in the brain. Cell Mol Neurobiol.
Summary: The authors of this study assessed levels of ACE2 expression in 85 human tissues including 21 brain regions, 7 fetal tissues and 8 controls. Strong ACE2 expression was seen in not only respiratory, digestive, renal-excretory and reproductive tissue, but also in the amygdala, cerebral cortex and brainstem. The greatest level of ACE2 expression was seen in the pons and medulla oblongata, which the authors suggest may somewhat explain the susceptibility of many COVID-19 patients to severe respiratory distress.
Publication date / reference: 25/08/20. De Virgiliis and Di Giovanni. Lung innervation in the eye of a cytokine storm: neuroimmune interactions and COVID-19. Nat Rev Neurol.
Summary: The authors of this study propose the concept of the “neuroimmune unit” as a key determinant of lung function in the context of COVID-19, inflammatory conditions and ageing, focusing especially on the involvement of the vagus nerve. They discuss the potential for neurostimulation and pharmacological neuromodulation to reduce tissue inflammation in order to prevent respiratory failure from COVID-19.
Publication date / reference: 10/07/20. Luzzi et al. Targeting of renin-angiotensin system in COVID-19 patients affected by stroke: Emerging concerns about detrimental vs. benefit effect. Interdiscip Neurosurg.
Summary: The authors conducted a retrospective case-note review of six patients affected by stroke while being on ACE inhibitors and Angiotensin-II receptor blockers. They call for randomized clinical trials to assess the safety profile and neuroprotective properties of ACEIs and ARBs in COVID-19 patients.
Publication date / reference: 02/07/20. Canham et al. Electroencephalographic (EEG) features of encephalopathy in the setting of Covid-19: A Case Series. Clin Neurophysiol Pract.
Summary: The authors report their clinical findings from a convenience sample of ten COVID-19 patients who had received EEG in ITU. They typically found widespread slow activity (mainly delta) with a mild anterior emphasis. They concluded that the general EEG picture was consistent with encephalopathy but non-specific for any underlying aetiology, and may have represented effects of hypoxia, sepsis, medications, previous seizure or metabolic derangements. Generalisability of the study may be limited by case selection.
Publication date / reference: 11/08/20. Neumann et al. Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms. J Neurol Sci.
Summary: Correspondence describing an observational case series of 30 COVID-19 patients who underwent LP, split nearly 50/50 between “critical” and “recovery” phases of the disease. WBC counts were normal or only slightly elevated in 28/30 cases. The CSF blood albumin ratio was normal in most tested cases but five had a severe disruption – perhaps more often in the critical disease phase. CSF was negative for SARS-CoV-2 in all cases and there was no evidence of unexplained CNS-specific oligoclonal bands. The authors conclude that their data imply most likely an indirect viral effect on the nervous system: cerebrovascular events, encephalopathies or neuropathies due to systemic critical illness and secondary immune phenomena. They note however that a negative PCR-test does not exclude the presence of the virus in the brain tissue, and case selection remains a perennial issue.
Publication date / reference: 08/07/20. Hamm & Rosenthal. Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of Coronavirus Disease-2019: Psychopharmacological Interactions and Neuropsychiatric Sequelae. Psychosomatics.
Summary: The authors review data on chloroquine and hydroxychloroquine relevant to psychiatry. Both drugs are mild enzyme inhibitors, and their levels may in turn be impacted by psychiatric drugs (check for interactions). Both chloroquine and hydroxychloroquine have been suspected to prolong the QT interval; however evidence is mixed and the clinical significance unclear. The most common CNS side effects of chloroquine are reportedly headache, dizziness, and insomnia. Cases of “psychosis after chloroquine” have been described, but the overall incidence is unknown. The authors acknowledge the limitations of extrapolating from research in other diseases like rheumatology and malaria to COVID-19, and call for research on the incidence and phenomenology of neuropsychiatric side effects in patients prescribed either drug.
Publication date / reference: 08/08/20. Bellon et al. Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients. Clin Infect Dis.
Summary: Single-centre retrospective observational study describing results from CSF analysis in 31 confirmed COVID-19 patients who had required LP for acute neurological symptoms or signs (mostly encephalopathy). A small majority were in ICU and the remainder largely in general hospital wards. SARS-CoV-2 RNA was undetectable in CSF in all cases. CSF/plasma albumin ratio was elevated in most, suggesting reduced integrity of the BBB. Most patients had matched CSF/serum oligoclonal bands and none had OBs specific to CSF. The authors concluded that their sample found no evidence of direct viral infection of the central nervous system, preferring instead the theory of passive diffusion of oligoclonal IgG from a systemic inflammatory state. Selection bias and the retrospective nature limit study generalisability.
Publication date / reference: 04/08/2020. Zhang et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Research.
Summary: In this study, researchers introduced SARS-CoV-2 to neural progenitor cells which had been derived from pluripotent stem cells and had formed neurospheres and brain organoids in in vitro lab conditions. They found evidence for SARS-CoV-2 replication with the cells, suggesting the potential for direct viral involvement in neuro symptoms in COVID-19 patients. The authors also suggest, worryingly for those with persistent anosmia, that the invasive potential of SARS-CoV-2 into neural progenitor cells may preclude recovery if the olfactory neurons are damaged. Usual limitations of in vitro studies apply here, and translational and clinical conclusions cannot be drawn with certainty.
Publication date / reference: 30/07/2020 Guilmot et al. Immune-mediated neurological syndromes in SARS-CoV-2-infected patients. J Neurol.
Summary: In this study the authors prospectively included all patients admitted to a multi-site Belgian hospital trust with new-onset neurological manifestations with confirmed SARS-CoV-2 swabs. Presentations included cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. Fifteen patients met their inclusion criteria, with CSF analyses available for 13 of these. A significant negative finding was that none of the patients had SARS-CoV-2 in their CSF analysis. Lymphocytic pleocytosis was found in two, with Anti-GD1b and anti-Caspr2 in two others respectively. The non-specificity of these CSF findings as well as overall low n preclude any definitive conclusions on the clinical relevance of these findings.
Publication date / reference: 16/06/2020 Kanberg et al. Neurochemical Evidence of Astrocytic and Neuronal Injury Commonly Found in COVID-19. Neurology.
Summary: Authors showed neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19 via measurement of plasma biomarkers of CNS injury (neurofilament light chain protein and glial acidic protein (GFAp).
Publication date / reference: 17/06/20 Yin et al. Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation During the COVID-19 Outbreak. ACS Chem Neurosci.
Summary: This brief narrative summary outlines a hypothesis that suppressing VEGF expression may reduce blood-brain barrier breakdown and attenuate neuroinflammation. The authors call for research into potential therapeutic mechanisms of VEGF-targeted drugs on the neurological manifestations of COVID-19.
Publication date / reference: 15/06/20 Mao et al. The COVID-19 Pandemic: Consideration for Brain Infection. Neuroscience.
Summary: This brief narrative summary presents a hypothesis that Sars-CoV-2 can enter the central nervous system via the olfactory nerves, and/or ACE-2 expression on brain tissues.
Publication date / reference: 15/06/20 Stip. Psychiatry and COVID-19: The Role of Chlorpromazine. Can J Psychiatry.
Summary: Correspondence advancing a blue-sky hypothesis that the antipsychotic drug Chlorpromazine may have efficacy against Sars-CoV-2, and calling for a clinical trial.
Publication date / reference: 12/06/20 Anoop et al. Happy Hypoxemia in COVID-19-A Neural Hypothesis. ACS Chem Neurosci.
Summary: This brief narrative summary proposes a hypothesis that SARS-CoV-2 mediated inflammation of the medullary nucleus tractus solitarius may impair the relay of afferent hypoxia stimuli from the carotid bodies, resulting in an impaired efferent respiratory response.
Publication date / reference: 12/06/20 Naughton et al. Potential Novel Role of COVID-19 in Alzheimer’s Disease and Preventative Mitigation Strategies. J Alzheimer’s Dis.
Summary: Mechanistic overview of the hypothesis that SARS-CoV-2 could accelerate the progression of neurodegenerative conditions like Alzheimer’s Disease. The authors discuss the role of interferons in the pathogenesis of COVID-19 and AD.
Publication date / reference: 01/06/20 Ray et al. A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction. Brain Behav Immun.
Summary: Using alveolar lavage samples from COVID-19 patients the authors identify neuro-immune interactions which may drive pulmonary dysfunction.
Publication date / reference: 26/05/20 Louis et al. Continuous Electroencephalography (cEEG) Characteristics and Acute Symptomatic Seizures in COVID-19 Patients. MedRxiv (preprint).
Summary: Retrospective cohort study of EEG recordings in patients with severe SARS-CoV-2 infection (continuous n=19, standard EEG n=3). EEG was conducted due to either new alteration in mental state or seizure-like activity. Encephalopathic COVID-19 positive patients had a range of EEG abnormalities, with 5 patients demonstrating epileptiform activity (2 had prior history of epilepsy).
Publication date / reference: 24/05/20 Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathologica.
Summary: Autopsy case report of a critically ill patient infected with SARS-CoV-2 who died in hospital. A range of neuropathological lesions were identified demonstrating vascular and demyelinating pathology. Interestingly, subcortical white matter revealed, a range of associated axonal injury, and a perivascular acute disseminated encephalomyelitis (ADEM)-like appearance.
Publication date / reference: 22/05/20 Flamand et al. Pay More Attention to EEG in COVID-19 Pandemic. Clin Neurophysiol.
Summary: Authors call for more attention to EEG findings in COVID-19. They present an 80-year-old encephalopathic patient with a normal MRI but with epileptiform activity and periodic triphasic waves on EEG, which have previously been documented in other neurotropic diseases.
Publication date / reference: 21/05/20 Schaller et al. Postmortem Examination of Patients With COVID-19. JAMA.
Summary: Case series (n=10) of patients with SARS-CoV-2 who died. Despite widespread histopathological findings of pulmonary and cardiac damage central nervous system involvement by COVID-19 could not be detected. Unfortunately, authors did not include any electron microscopy findings.
Publication date / reference: 20/05/20 Pastor et al. Specific EEG Encephalopathy Pattern in SARS-CoV-2 Patients. J Clin Med.
Summary: Review of the quantified EEG readings of SARS-CoV-2 patients in intensive care.
Publication date / reference: 08/05/20 Kandemirli et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology.
Summary: Multicentre retrospective study of ICU patients with neurologic symptoms. Acute MRI abnormalities seen in 12/27 (44%) had acute findings.
Publication date / reference: 08/05/2020 Coolen et al. Early postmortem brain MRI findings in COVID-19 non-survivors. MedRxiv (preprint)
Summary: Postmortem brain MRI study of 19 COVID-19 patients. Authors demonstrated hemorrhagic and posterior reversible encephalopathy syndrome-related brain lesions in non-survivors of COVID-19 that they suggest might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seemed to be limited to olfactory bulbs (♦).
Publication date / reference: 21/04/2020 Paniz-Mondolfi A et al. Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). J Med Virol.
Summary: Single case report of virus detected by TEM (transmission electron microscopy) in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem of patient with respiratory symptoms and confusion(♦).
Publication date / reference: 22/04/2021 Parsons et al., Modelling the Anatomic Distribution of Neurologic Events in Patients with COVID-19: A Systematic Review of MRI Findings Am J Neuroradiol.
Summary: The authors in this study aimed to quantitatively evaluate whether a network diffusion model can explain the spread of small neurologic events.The MEDLINE, EMBASE, Scopus, and LitCovid databases were searched from January 1, 2020, to July 19, 2020.Within gray matter, neurologic events were widely distributed, with the largest number of events (∼10%) observed in the bilateral superior temporal, precentral, and lateral occipital cortices, respectively.
Publication date / reference: 22/03/2021 Khedr et al. Clinical and Radiological Characteristics of Acute Cerebrovascular Diseases Among Egyptian Patients With COVID-19 in Upper Egypt. eCollection 2021.
Summary: In their retrospective observational study Khedr et al. compare 55 COVID-19 patients with acute cerebrovascular disease with 250 non-COVID-19 stroke patients. Their findings include a significantly greater proportion of large vessel occlusion, and comorbidities such as hypertension, ischaemic heart disease, hepatic and renal disease in those with COVID-19.
Publication date / reference: 01/03/2021 Lambrecq et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw Open.
Summary: The authors of this French retrospective cohort study assessed EEG data on 78 COVID-19 patients, 69 of whom showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhaemorrhages, and white matter-enhancing lesions. CSF analysis was negative for SARS-CoV-2 for all tested patients. Nine patients with no identifiable cause of brain injury outside COVID-19 were identified; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions.
Publication date / reference: May 2021. Rehmani et al. Spectrum of neurologic & neuroimaging manifestation in COVID-19. Brain Behav Immun Health.
Summary: A case series of 16 patients with COVID-19 who presented mainly with neurological findings, and had acute radiological brain changes on Computed Tomography (CT) scan. The most common neuroimaging features were ischemic infarcts, a combination of ischemia and acute white matter changes, temporal lobe predominant encephalopathic changes, and isolated cortical or more extensive intracranial hemorrhages.
Publication date / reference: 11/03/2021 Mahammedi et al. Brain and lung imaging correlation in patients with COVID-19: could the severity of lung disease reflect the prevalence of acute abnormalities on neuroimaging? A global multicenter observational study. AJNR Am J Neuroradiol.
Summary: The authors of this retrospective, international multicenter observational study reviewed electronic medical records and imaging of 135 hospitalised patients with COVID-19. Patients with acute abnormal neuroimaging findings had significantly higher mean CT lung severity score and were more likely to present with ischaemic stroke. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. Neuroimaging findings in these patients included acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%).
Publication date / reference: 01/03/2021 Lindan et al. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study. Lancet Child Adolesc Health.
Summary: In this international multi-site study, 38 children with covid-19 associated neurological manifestations were recruited for neuroimaging. Numerous types of imaging abnormalities were noted, including ADEM (n = 16), CNS myelitis (n = 8), and non-specific hyperintesities (n = 13).
Publication date / reference: 18/02/21. Uncini et al. Electrophysiological features of acute inflammatory demyelinating polyneuropathy associated with SARS-CoV-2 infection. Neurophysiol Clin.
Summary: in this comparison of the electrophysiological signatures of SARS-CoV-2 associated acute inflammatory demyelinating polyneuropathy (AIDP), the authors compared 24 cases with 48 controls with AIDP unrelated to COVID-19. They identified some putative characteristic hallmarks of s-AIDP, including additional muscle fibre conduction slowing and α-motor neuron hypoexcitability.
Publication date / reference: 15/2/21 Conklin et al. Susceptibility-weighted imaging reveals cerebral microvascular injury in severe COVID-19. J Neurol Sci.
Summary: Conklin and colleagues’ aim for this prospective cohort study was to find histopathological and radiological correlates of microvascular lesions in patients infected with COVID-19 meeting clinical criteria for severe illness (n=16). MRI brain and susceptibility-weighted imaging (SWI) were used, and showed diffuse microvascular injury to subcortical and deep white matter in 69%. The patterns of SWI injury were similar to hypoxic respiratory failure, sepsis and disseminated intravascular coagulation. These findings can shed light on the mechanisms of cerebral injury in COVID-19 with therapeutic and diagnostic potential.
Publication date / reference: 01/2021 Khandwala et al. Imaging Patterns of Encephalopathy in Patients with COVID-19. J Coll Physicians Surg Pak.
Summary: The authors of this retrospective observational study assessed neuroimaging in 12 COVID-19 patients with neurological symptoms predominantly including seizures and altered mentation. Three cases had acute watershed infarcts, two cases had posterior cerebral artery territorial infarcts, two cases had periventricular corona radiata infarcts, three cases had hypoxic ischemic encephalopathy, two cases had posterior reversible encephalopathy syndrome, and there was one case each of cerebral venous sinus thrombosis, pontine infarct, and bithalamic lesions.
Publication date / reference: 05/03/2021 Agarwal et al. Increase in Ventricle Size and the Evolution of White Matter Changes on Serial Imaging in Critically Ill Patients with COVID-19. Neurocrit Care.
Summary: This retrospective, New York multicentre, cohort study aimed to look at serial MRI changes of patients who were critically ill with COVID-19. They reviewed 4530 patients who were critically ill and admitted to three tertiary care hospitals in New York and found 21 patients with two MRIs separated by a median of 22 days. They found that ventricular size increased over several weeks and white matter changes were found on every patient, they often remained unchanged, but in a smaller proportion they worsened (7/21) or improved (3/21) over time.
Publication date / reference: 05/03/2021 Lindan et al. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study Lancet Child Adolesc Health
Summary: An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients).
Summary: The authors of this international study identified 38 children with neurological disease related to SARS-CoV-2 infection from eight different countries. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement was noted to potentially occur in the absence of corresponding neurological symptoms.
Publication date / reference: 15/01/21 Conklin et al. Susceptibility-weighted imaging reveals cerebral microvascular injury in severe COVID-19. J Neurol Sci.
Summary: The authors of this retrospective observational study evaluated neuroimaging (susceptibility-weighted imaging MRI) findings from patients admitted to intensive care with COVID-19 and where neuroimaging was indicated to evaluate unresponsiveness (n=11) or focal neurological deficits (n=5). In 11 patients, diffuse microvascular injury involving the subcortical and deep white matter was detected – preferentially involving the corpus callosum and the subcortical and deep white matter. This distribution is concordant with brain abnormalities observed in patients with severe sepsis and hypoxic respiratory failure.
Publication date / reference: 04/01/2021 Aragao et al., Comparative Study – The Impact and Profile of COVID-19 Patients Who Are Indicated for Neuroimaging: Vascular Phenomena Are Been Found in the Brain and Olfactory Bulbs (MedRxiv)
Summary: This retrospective two-centre study compared confirmed COVID-19 infected (n=232) patients who were indicated for brain imaging (n=35) and those who were only indicated for chest imaging (n=197). They noted that the brain imaging patients had no symptomatic difference but showed increased severity of disease and increased likelihood of ICU admission. In addition, of these 35 patients, 40% had abnormal brain imaging; in which all had vascular brain lesions (22.9% bleeding, 8.6% restricted diffusion lesions). On evaluating the olfactory bulbs of these patients where possible (n=12) they found enhancement/bleeding. They suggest this may be due to SAR-COV-2 entry via olfactory mucosa to the cribriform plate.
Publication date / reference: 15/01/2021. Conklin e