By Matt Butler, Cameron Watson, Ally Rooney, Jia Song, Jamie Badenoch, Susannah Pick, Ben Cross, Danish Hafeez, Mao Fong Lim, Hamilton Morrin, Emma Rengasamy, Lucy Thomas, Sylvia Ralovska, Ritika Sundaram, Earl Aniwattanapong, Dean Walton, 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 11th-17th November
This week we have summarised 66 papers on the neurology and neuropsychiatry of covid-19.
Emerging evidence of ‘Long-COVID’
Recent weeks have seen increasing media discussion regarding the long-term effects of COVID-19 or ‘Long-COVID’. This week, Mandal et al.’s cross-sectional study of 384 individuals across three large London hospitals, serves to significantly contribute to said discussion by offering 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.
Elsewhere in Ireland, Towsend et al. investigate the rate of fatigue (Chalder Fatigue Scale (CFQ-11)) in COVID-19 patients after physical recovery more than 6 weeks from the initial illness. The authors reported a high prevalence of fatigue (50%) at median follow up of 10 weeks in these patients, 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 was found between routine laboratory markers of inflammation and cell turnover, or pro-inflammatory molecules 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 SARS-CoV-2 infection regardless of the initial disease severity, and highlights the need for larger cohort, longitudinal studies of COVID -19 patients.
Other news in brief
Coming soon: the latest from MedRxiv
We did not identify any relevant preprints this week. Keep an eye out next week!
Case report roundup
Particularly towards the beginning of the pandemic, there were a number of case reports which detailed cases of de novo transient psychoses in patients without any past psychiatric history. Almost invariably, these cases were in the absence of confirmed covid-19 infection. In their BMJ Case Reports article, Gillet & Jordan report on a similar case in a healthcare worker, but in this case in the context of confirmed covid-19 infection. The authors point out that the physiological effects of the infection, the psychological stress of the patient’s job, and other social aspects such as racial discrimination were likely to be equally implicated in the genesis of this patient’s psychosis and suicide attempt.
Case reports of rarer neurological causes of profound illness in young people with covid-19 are sadly still arising. Bin Adbul Sattar et al. report on a 25-year-old with covid-19 who developed locked-in syndrome due to bilateral pontine infarction during the course of her illness; they cited covid-19 coagulopathy as a precipitating factor. In their case report, Yousefi et al. report on a case of viral meningitis in a nine year old; of important note, CSF PCR was positive for covid-19. Thankfully, after successful treatment this young person recovered and was discharged after ten days.
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: 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: 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.
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: 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: 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: 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: 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: 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: 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.
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: 10/11/2020. Leila Simani et al. The outbreak of methanol intoxication during COVID-19 pandemic: prevalence of brain lesions and its predisposing factors. Drug Chem Toxicol.
Summary: This retrospective study aimed to evaluate the prevalence and predisposing factors of brain lesions in patients with methanol toxicity and its outcome. 40 out of the 516 enrolled patients with confirmed methanol poisoning underwent spinal brain computed tomography (CT). The results showed that putaminal or subcortical white matter haemorrhage, lower initial GCS, and lower bicarbonate levels were indicators of mortality in methanol toxicity. The authors concluded that the association between methanol poisoning with increased morbidity and mortality should be considered a greater threat during COVID-19.
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Summary: Rapalino and colleagues present the findings from three consecutive patients with COVID-19 who underwent 3D brain multivoxel MR spectroscopic imaging. The data collected from the three patients with COVID-19 was compared to that of two patients with leukoencephalopathy and one healthy age-matched control. Out of the three patients with COVID-19 included in the series, one patient had COVID-19 related necrotising leukoencephalopathy, another had suffered a pulseless electrical activity cardiac arrest and had subtle white matter changes, and the final patient hadn’t presented with any signs of encephalopathy and hadn’t had a recent severe hypoxic episode. Overall, it was found that the patients with COVID-19 associated necrotising leukoencephalopathy and the patient with COVID-19 postcardiac arrest both showed a pattern of NAA reduction, coline elevation and glutamine/glutamate elevation seen in the patient with delayed post-hypoxic leukoencephalopathy.
Publication date / reference: 13/10/20. Skorin et al. EEG findings and clinical prognostic factors associated with mortality in a prospective cohort of inpatients with COVID-19. Seizure.
Summary: Multicentric prospective observational study of 94 EEG in patients with COVID-19 (n=62). The most frequent EEG finding was generalized continuous slow-wave activity (66 %). Epileptic activity was observed in 19% of the cases. Periodic patterns were observed in 3 patients (3.2 %). Interestingly, using multivariate analysis the authors found requiring an EEG during the third week of evolution is linked to a higher risk of mortality, they postulated that this may relate to the hyper-inflammatory phase of a cytokine storm, which accompanies severe respiratory distress syndrome, altered consciousness level and multiorgan failure. As pointed out by the authors, findings from the study should be taken with caution given the relative small sample size.
Publication date / reference: 15/09/2020. Sawlani et al. COVID-19-related intracranial imaging findings: a large single-centre experience. Clin Radiol.
Summary: A retrospective review of 3,403 patients with SARS-CoV-2 infection. Of these, 167 (4.9%) had neurological signs or symptoms warranting neuroimaging. Neuroimaging showed abnormalities in 23% of patients, with MRI being abnormal in 20 patients and CT in 18 patients. The most consistent neuroradiological finding was microhaemorrhage. Other findings include acute haemorrhagic necrotising encephalopathy, white matter hyperintensities, hypoxic-ischaemic changes, ADEM-like changes, and stroke. Prolonged hypoxaemia, consumption coagulopathy, and endothelial disruption are the likely pathological drivers.
Publication date / reference: 06/09/20. Radnis et al. Radiographic and clinical neurologic manifestations of COVID-19 related hypoxemia. J Neurol Sci.
Summary: The authors retrospectively describe three cases of hypoxic brain injury seen on MRI, along with clinical correlations, in patients with hypoxemia secondary to COVID-19 related ARDS. None of the patients experienced cardiopulmonary arrest. Despite the lack of severe observed hypoxemia in two of the three patients, these patients developed hypoxic brain injury. The same two patients developed cytokine release syndrome (CRS). The authors propose that CRS may be a contributing factor to the prolonged encephalopathy reported in two of the patients. They remind readers that we may see more patients with long-term neurocognitive sequelae that are recognised to follow critical illness. Neurorehabilitation after hospitalization will be important to improve the functioning and quality of life of these patients.
Publication date / reference: 10/09/20. Yoon et al. Clinical and Neuroimaging Correlation in Patients with COVID-19. AJNR Am J Neuroradiol.
Summary: The authors of this retrospective neuroimaging study, characterised the frequency of intracranial abnormalities in patients with COVID-19 who underwent CT/MRI brain imaging (n=150). 17% had abnormal CT and/or MR imaging findings, with hemorrhage in 42% of the patients, infarction in 50% of the patients, and leukoencephalopathy in 27% of the patients. Interestingly, the authors detected a significant association between abnormal CT/MR imaging findings and intensive care unit admission, intubation and acute kidney injury.
Publication date / reference: 26/08/20. Louis et al. Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients. Clin Neurophysiol.
Publication date / reference: 16/09/20. Tsivgoulis et al. Olfactory bulb and mucosa abnormalities in persistent COVID-19 induced anosmia: a Magnetic Resonance Imaging study. Eur J Neurol.
Summary: This study utilised MRI imaging in adult, non-hospitalised patients with self-reported persistent olfactory dysfunction for >39 days post symptom onset in Greece. Objective olfactory assessment was performed using the three-odorant test. Rhinosinusitis was ruled out using the SNOT 22 questionnaire. Neuroimaging evaluation of the cases (n=8) and age and sex matched historical controls was performed via MRI. The imaging showed bilateral reduced olfactory bulb height in cases vs controls, indicative of mild atrophy in 88% of the patients. Moreover, MRI revealed olfactory mucosa thickening in four cases. The authors concluded that they had demonstrated lower olfactory bulb heights in COVID-19 patients compared to age and sex matched controls, however, they noted the small sample size as a limitation of the study.
Publication date / reference: 16/09/20. Edjlali et al. Teaching NeuroImages: Cytotoxic lesions of the corpus callosum (CLOCCs) in encephalopathic patients with COVID-19. Neurology.
Summary: The authors present images from two patients with COVID-19 in whom brain MRI revealed lesions of the splenium of the corpus callosum. They call it “Cytotoxic Lesion Of the Corpus Callosum (CLOCC)”, which they state is characterised as a non-ischemic lesion, usually transient and reversible, and mechanistically said to reflect a vulnerability of the splenium of the corpus callosum to cytokinopathy.
Publication date / reference: 11/09/20. Eliezer et al. Loss of smell in COVID-19 patients: MRI data reveals a transient edema of the olfactory clefts. Neurology.
Summary: Debate continues as to what extent the loss of smell in SARS-CoV2 infection is caused by congestion in the olfactory clefts and/or direct damage to the olfactory sensory neurons, causing structural changes in the olfactory bulb and pathways. Noting this, the authors conducted a prospective controlled cohort study comparing the MRI findings of 20 confirmed COVID-19 patients with olfactory function loss, with 20 age-matched healthy controls. Sampling timepoints were at baseline shortly after the onset of anosmia, and again one month later. Imaging at a baseline mean of six days after the onset of anosmia, the authors found morphological changes consistent with obstruction of the olfactory clefts in 19/20 patients, and no controls. One month later there was a significant decrease in OC obstruction, but a minority continued to display unilateral obstruction, in association with ongoing dysosmia. No significant differences in the volume of the olfactory bulb were observed between patients and controls either at baseline or at one-month follow-up. The authors conclude that a proportion of COVID-19 associated anosmia may be due to congestion of the olfactory clefts preventing odorant molecules from reaching the olfactory epithelium. Addressing the potential objection that most patients did not report significant nasal congestion, the authors speculated that with only 10% of inhaled air said to reach the olfactory clefts during normal resting breath, patients may be symptomatically unaware of obstruction. The small number of patients in the study – especially those with persisting anosmia – limits the conclusions which can be drawn, but the study comes down clearly on the side of those hypothesising mechanical obstruction as a cause of anosmia in COVID-19.
Summary: From n=2820 confirmed and hospitalised COVID-19 patients, the authors retrospectively surveyed the results of 59 patients who had received brain MRI. Six patients 6 (10.2% of scanned sample) had acute infarcts and a further six patients had neuroimaging findings suggestive of COVID-19 related disseminated leucoencephalopathy (CRDL). All patients with CRDL had white matter T2/FLAIR abnormalities, which were confluent in four and multifocal in two, and most frequently affected the periventricular, subcortical, and deep white matter. Patchy, asymmetric abnormal FLAIR signal was also seen in the corpus callosum (5/6; 83.3%), brain stem (4/6; 66.7%), and cerebellum (4/6; 66.7%), including one patient with lesions involving bilateral middle cerebellar peduncles. The study is at high risk of ascertainment bias because patients were selected for MRI by the treating clinicians.
Publication date / reference: 08/09/20. Sheth et al. Assessment of brain injury using portable, low-field magnetic resonance imaging at the bedside of critically ill patients. JAMA Neurol.
Summary: The authors of this prospective, single-center cohort study assessed 50 patients admitted to the neuroscience or COVID-19 intensive care units at Yale New Haven Hospital, 20 of whom had COVID-19 and had presented with altered mental status. 8 of 20 COVID-19 patients demonstrated abnormalities on portable MRI and no adverse events or complications arose from use of portable MRI in the intensive care unit room.
Publication date / reference: 02/09/20. Pellinen et al. Continuous EEG findings in patients with COVID-19 infection admitted to a New York academic hospital system. Epilepsia.
Summary: This study examined medical records and EEG studies of all patients hospitalised with confirmed COVID-19 infections over a 2-month period at a US academic health system. 111 patients underwent 118 EEG studies. 71% of the population were male and the median age was 64 (IQR 17). The majority of patients were critically ill at the time of EEG monitoring; 77% were in ITU, 72% mechanically ventilated and 70% were comatose. EEG monitoring started a median of 10.8 (IWR 17.3) days after hospitalisation and the median duration was 1.3 (IQR 1.3) days. The most frequent EEG finding was moderate generalised slowing (57%) and epileptogenic findings were observed in 30%. Seizures were noted in 7% of the patients. Independent predictors of epileptiform were a history of epilepsy (OR 5.4, 95% CI 1.4-2.1, p=0.015) and having a definite or suspected clinical seizure prior to EEG testing (OR 4.8, 95% CI 1.7-1.3, p=0.002). The authors concluded by stating that they had reported the first large series of EEG findings associated with COVID-19 infections.
Publication date / reference: 03/09/20 Gulko et al. MRI Brain Findings in 126 Patients with COVID-19: Initial Observations from a Descriptive Literature Review. AJNR Am J Neuroradiol.
Summary: Non-systematic literature review of twenty-two articles concerning MRI findings in patients infected with SARS-CoV-2 (n=126). Infarcts, both acute and subacute were the most frequent diagnosis. Other findings included leukoencephalopathy with micro-haemorrhages, leptomeningeal contrast enhancement and cortical FLAIR signal abnormality. The authors concede a more systematic approach will be required as more articles are published.
Publication date / reference: 03/09/20. Toledano-Massiah et al. Unusual Brain MRI Pattern in 2 Patients with COVID-19 Acute Respiratory Distress Syndrome. AJNR Am J Neuroradiol.
Summary: In this case series, Toledano-Massiah and colleagues present two cases of patients with PCR-confirmed COVID-19 admitted to their intensive care unit with similar imaging findings on MRI. Both patients presented with sepsis secondary to ventilator-associated pneumonia and had delayed recovery of consciousness after prolonged sedation. In both cases there were nodular and ring shaped lesions involving the periventricular and deep white matter which were hyperintense on DWI and FLAIR; the corpus callosum was also involved. The authors concluded that the etiology and pathophysiology of these lesions is unclear.
Publication date / reference: 29/08/2020 Castellano et al. Pathological brain CT scans in severe COVID-19 ICU patients. Intensive Care Medicine.
Summary: A single-center retrospective analysis on brain CT findings in 23 patients with COVID-19 infection admitted to ITU. Brain CT scans demonstrated acute lesions in 9 out of 23 cases (39%), abnormalities were hemorrhagic in most of these cases.
Publication date / reference: 03/08/20. Lu et al. Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study. EClinicalMedicine.
Summary: The authors examined volumetric and diffusion measurements in recovered COVID-19 patients, in an effort to study potential long-term brain structural changes related to SARS-CoV-2. They enrolled 60 recovered COVID-19 patients (mean 97 days post-onset, mostly mild cases) and compared their imaging with 39 age- and sex-matched non-COVID-19 controls. MRI showed higher grey matter volume in bilateral olfactory cortices, hippocampi, insulas, left Heschl’s gyrus, left Rolandic operculum and right cingulate gyrus. The authors noted that all these structures contribute to the central olfactory system. They speculated that the increased volume may be due to adult neurogenesis from the sub-ependymal zone, or to increased functional connectivity. Meanwhile DTI showed reduced diffusion and elevated fractional anisotropy. The authors speculate that this pattern suggests a greater alignment of fibers and limited diffusion freedom perhaps secondary to remyelination. The study also provides some limited medium-term outcome data of symptomatology in survivors: contrary to other emergent studies, the reported prevalence of fatigue and mood symptoms decreased significantly at follow-up compared to during the acute illness.
Publication date / reference: 14/08/2020. Notz et al. Severe neurological complications in critically ill COVID-19 patients. J Neurol.
Summary: In this case series, Notz and colleagues retrospectively reviewed the notes of patients with COVID-19 (PCR confirmed) admitted to their Intensive Care Unit. Neurological complications were found in nine cases. Seven patients had potentially life-threatening neurological events in which two cases occurred during veno-venous extracorporeal membrane oxygenation (ECMO) therapy. Three patients suffered from intracerebral haemorrhage. One patient sustained a subarachnoid haemorrhage and another had multiple small intracerebral bleedings of septic-embolic aetiology. Two patients had generalised seizures, likely due to septic encephalitis. Two patients suffered from transient paresis and aphasia. From this case series, it is not possible to infer whether these neurological complications are specifically associated with SARS-Cov-2 infection.
Publication date / reference: 24/07/2020. Conklin et al. Cerebral microvascular injury in severe COVID-19. medRxiv. (Preprint)
Summary: In this observational retrospective cohort study, Conklin and colleagues investigated the microvascular lesions in patients with PCR-confirmed COVID-19 admitted to intensive care, as indicated by a susceptibility weighted imaging (SWI) MRI sequence. SWI lesions were identified in the subcortical and deep white matter regions (n=11) and in the corpus callosum (n=4). Eight patients had >10 SWI lesions. Brain autopsy in one patient with SWI lesions evidenced widespread microvascular injury including petechial haemorrhages and microscopic ischaemic lesions. The authors conclude that patients with COVID-19 are at risk of microvascular lesions in subcortical and deep white matter. This study is limited by being conducted at a single academic centre and its small sample size.
Publication date / reference: 30/07/20. Klironomos et al. Nervous System Involvement in COVID-19: Results from a Retrospective Consecutive Neuroimaging Cohort. Radiology.
Summary: This is a retrospective neuroimaging study of 185 patients with PCR-confirmed COVID-19. Where present, brain MRI abnormalities (n=43) were most commonly located inter-axially, with a predilection to the corpus callosum and juxtacortical areas. In terms of morphology the abnormalities were indicative of microvascular pathology. Leukoencephalopathy was a common finding (18/41). The authors suggested that these findings could be due to a combination of pathological processes including hypoxia, ischaemia and thrombosis. The authors did not report the indication for neuroimaging nor were the clinical deficits described. The findings are limited by the heterogeneous nature of the sample which included a broad spectrum of disease severity.
Publication date / reference: 30/7/20. Guedj. 18 F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders? Eur J Nucl Med Mol Imaging.
Summary: Preliminary findings in two case reports of neurological invasion of SARS-Cov-2 through the olfactory bulb. PET scans were performed in two COVID-19 patients requiring ITU admission in order to visualise lung hypermetabolism spots. No lung hypermetabolism was noted in either patient. However, neural hypometabolism of the bilateral rectal gyrus and right olfactory gyrus was found in one patient, and extended bilateral marked hypometabolism was identified involving the olfactory/rectal gyrus, amygdala, hippocampus, parahippocampus, cingulate cortex, bilateral thalamus, hypothalamus, cerebellum, pons and medulla. Variances in metabolism were achieved by comparing each patient to a local database of 24 healthy subjects selected on the same median age. CT scans were subsequently clear.
Publication date / reference: 18/7/20. Pasini et al. EEG findings in COVID-19 related encephalopathy. Clin Neurophysiol.
Summary: In this retrospective case series, Pasini and colleagues, reported EEG findings from patients with suspected COVID-19 related encephalopathy (PCR-positive) admitted to their hospital over a 3 month period (n=15). There was absence of reactivity to external stimuli in 10 patients. The EEGs were abnormal in all cases. In two patients with post-anoxic coma, the was severely suppressed activity and discontinued activity. In the remaining patients, there was slowing of background activity (n=9), focal theta or delta waves over frontal and central regions (n=3) and FIRDA (n=1). Pasini and colleagues hypothesise that COVID-19 related encephalopathy may be associated with diffuse slowing of background activity and loss of reactivity to external stimuli. However, due to the small sample size and lack of control sample, its not possible to infer whether these EEG findings are specific for COVID-19 related encephalopathy.
Publication date / reference: 25/06/20. Petrescu et al. Electroencephalogram (EEG) in COVID-19: A systematic retrospective study. Neurophysiol Clin.
Summary: This retrospective study reviewed EEGs from 36 patients with COVID-19 (all PCR confirmed) and neurological abnormalities, most commonly confusion or fluctuating awareness. The majority of patients (23/36) had normal or mildly altered EEG recordings. The abnormal findings could not be stereotyped across individuals, or stratified according to clinical presentation. The abnormalities included generalized periodic discharges, multifocal periodic discharges and rhythmic delta activity.
Publication date / reference: 15/07/20. Ayub et al. Clinical Electroencephalography Findings and Considerations in Hospitalized Patients with Coronavirus SARS-CoV-2. (MedRx pre-print, not peer-reviewed)
Summary: This retrospective study evaluated the EEG findings from 37 patients with COVID-19 (all were RT-PCR confirmed) and neurological abnormalities (mostly altered mental status). Epileptiform changes were detected in 14 of the patients and interestingly these patients were more likely to have pre-existing brain pathology (concordant with prior research). However, acute brain pathology did not significantly differ between patients with or without epileptiform changes, suggesting these electrophysiological abnormalities are more indicative of prior brain pathology than viral complication. Unsurprisingly, patients who were recently sedated had a higher incidence of background rhythm abnormalities (namely a lack of a posterior dominant rhythm).
Publication date / reference: 17/07/20. Chougar et al. Retrospective Observational Study of Brain Magnetic Resonance Imaging Findings in Patients with Acute SARS-CoV-2 Infection and Neurological Manifestations. Radiology.
Summary: The authors reported a single-centre retrospective case-note review of patients referred for brain MRI in the context of COVID-19. They included 73 COVID-19 patients (67 PCR-proven, six highly likely based on chest CT; CSF was PCR negative in all tested patients). No significant abnormalities were found in 30; of the reminder, ischaemic infarct, perfusion abnormalities, or micro-haemorrhages were the most often observed. Multifocal enhancing white matter lesions, foci of restricted diffusion in the corpus callosum, PRES, and neuritis were seen in a small number of cases each. A few had a novel pattern of basal ganglia involvement including signal and diffusion abnormalities, with variable contrast enhancement, affecting the substantia nigra, the globus pallidus and the striatonigral pathway. Prospective imaging-pathology correlation studies will be required to test causal relationship between COVID-19 and brain MRI lesions.
Publication date / reference: 17/07/20. Girardeau et al. Confirmed central olfactory system lesions on brain MRI in COVID-19 patients with anosmia: a case-series. MedRxiv pre-print (not peer-reviewed)
Summary: this is a case series of ten patients with COVID-19 (PCR-confirmed) and anosmia who underwent brain MRI. Three of the subjects had a severe and persistent loss of smell on an olfactory test (Sniffin Sticks test) and these patients interestingly had hypersignal intensity lesions of the central olfactory system on MRI. Two other patients with significant smell disorders had signs of mucosal hyperplasia of the upper nasal cavities. Whereas, no MRI abnormalities were found in two subjects who had good smell restoration. The results of this small sample suggest a central olfactory disturbance may underlie anosmia in severe cases of sensory deficit in COVID-19.
Publication date / reference: 10/07/20. Burgos-Blasco et al. Optic Nerve Analysis in COVID-19 Patients. J Med Virol.
Summary: The authors aimed to report changes in the optic nerve (per retinal nerve fibre layer thickness, RNFLT) using Optical Coherence Tomography (OCT). In a small case series (n=5) of SARS-CoV-2 PCR-positive patients who also had pre-pandemic baseline OCT measurements, seven out of eight examined eyes displayed an increase in RNFLT (mean increase in thickness= 4.3 microns). The authors speculate that viral-induced inflammation may underlie the changes, but its clinical significance will need further study.
Publication date / reference: 01/07/20. Pilato et al. EEG findings in coronavirus disease. J Clin Neurophysiol.
Summary: This case series described the EEG findings from eight patients with COVID-19 and neurological findings (most commonly an altered level of consciousness). EEG abnormalities were noted in all patients (generalised background slowing) and three patients had generalized epileptiform discharges. It is worth noting that five patients had a prior epilepsy diagnosis and the authors hypothesised that pre-existing epilepsy could be a risk factor for COVID-19-associated neurological manifestations.
Publication date / reference: 08/07/20. Fitsiori et al. Unusual microbleeds in brain MRI of Covid-19 patients. J Neuroimaging.
Summary: This case series described the MRI findings from nine patients with severe COVID-19 and neurological manifestations (altered level of consciousness or psychomotor agitation) whilst weaning from ventilatory support. Interestingly, all patients had an unusual distribution of microbleeds, which clustered in the corpus callosum. A similar pattern of neuroimaging findings has been described elsewhere in patients with COVID-19 neurology.
Publication date / reference: 24/06/20. Vellieux et al. COVID-19 associated encephalopathy: Is there a specific EEG pattern? Clin Neurophysiol.
Summary: The authors report on two cases of severe COVID-19 infection, both requiring ICU admission, with similar EEG patterns (non-reactive bifrontal monomorphic diphasic periodic delta slow waves), not previously reported. The mechanisms underlying these unusual electrophysiological abnormalities require further probing and whether they represent a signature of COVID-19 infection.
Publication date / reference: 25/06/20. Lang et al. Leukoencephalopathy Associated with Severe COVID-19 Infection: Sequela of Hypoxemia? AJNR Am J Neuroradiol.
Summary: A report of 6 critically ill patients with COVID-19 infection who had altered mental status, neurological manifestations and neuroimaging findings indicative of leukoencephalopathy. The authors hypothesise that these, albeit non-specific, neuroimaging findings could represent a delayed response to profound hypoxaemia experienced during the acute infection (all 6 patients required intubation for hypoxic respiratory failure).
Publication date / reference: 16/06/2020 Coolen et al. Early Postmortem Brain MRI Findings in COVID-19 Non-Survivors. Neurology.
Summary: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs.
Publication date / reference: 16/06/2020 Kremer et al. Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study. Radiology.
Summary: Retrospective MRI brain study of patients with severe COVID-19 and neurological manifestations. There were a diverse number of lesions noted, with no single distinct neuroradiological patterns. Only one patient was positive for SARS-CoV-2 RNA in the cerebrospinal fluid.
Publication date / reference: 11/06/20. Pons-Escoda et al. Neurologic Involvement in COVID-19: Cause or Coincidence? A Neuroimaging Perspective. Am J Neuroradiol.
Summary: Single-centre retrospective cross-sectional review of 103/2249 patients diagnosed with COVID-19 who underwent neuroimaging on clinical grounds. The most common reasons for scanning were mild and/or non-specific neurological complaints, e.g. headache, and nearly all of these referrals had normal scans. By contrast more than ⅔ of patients with a clinical stroke had it confirmed by scan.
COVID-19 in pre-existing neuropsychiatric groups
Publication date / reference: 16/11/2020 Vignatelli et al. Risk of hospitalization and death for COVID-19 in people with Parkinson’s disease or parkinsonism. Mov Disord.
Summary: In this retrospective study, authors compared admission rates for covid-19 in patients with Parkinson’s to those without. They found that compared to matched controls, patients with Parkinson’s Disease were less likely to be admitted (HR 0.8), although those with parkinsonism were much more likely (HR 3.3). There were no differences in the fatality rates between groups. Of course, there are a number of confounders, such as the likelihood of reduced activity and outside contacts that a patient with Parkinson’s is likely to have.
Publication date / reference: 01/11/2020. Kubota and Kuroda, Exacerbation of neurological symptoms and COVID-19 severity in patients with preexisting neurological disorders and COVID-19: A systematic review. Clin Neurol Neurosurg.
Summary: This systematic review aimed to evaluate the severity of COVID-19 and its effect on neurological symptoms in patients with preexisting neurological disorders and concurrent COVID-19. Among 232 patients, 74 (31.9 %) showed exacerbation of preexisting neurological symptoms of dementia (55/92; 59.5 %), Parkinson’s disease (10/17; 58.8 %), epilepsy (1/1; 100 %), and unspecified neurological disorders (8/106; 7.5 %). Apart from infection, some of the factors discussed include the disruption of usual care and adherence to medication regimes. Of 2168 patients, 478 (22.0 %) showed severe COVID-19 course (defined as requiring ICU admission). These included patients with cerebrovascular disease (86/445; 19.3 %), dementia (70/316; 22.2 %), Parkinson’s disease (25/214; 11.7 %), multiple sclerosis (28/71; 39.4 %), spinal cord injury (5/7; 71.4 %), epilepsy (10/98; 10.2 %) and unspecified neurological disorders (254/1011; 25 %). The authors note that this review is limited by bias, given that most of the included studies were case reports or small cohort studies, which may have missed out milder cases.
Publication date / reference: 30/10/2020 Salahuddin et al. Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19. Front Neurol.
Summary: In this retrospective study, the authors aimed to examine the bidirectional association between neurological disorder and admission to hospital with covid-19. They found that patients with a history of neurological disease (dementia, stroke, epilepsy, traumatic brain injury, MS, Parkinson’s disease, and developmental delay) had a higher mortality (31% vs 15%), however that it was not a predictor of death in their statistical models. Flipping the association around, the mortality rate of patients with neurological manifestations secondary to covid-19 (encephalopathy, stroke, or seizures) was much higher than controls (37% vs 12%), and was a predictor of death (OR 2.1). Of course, on the latter point, neurological manifestations are often associated with more severe disease, therefore their predictive model may simply be selecting for patients who have worse outcomes due to worse disease, rather than because of the neurological manifestations per se.
Publication date / reference: Louapre et al. Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders. Eur J Neurol.
Summary: This multicentre French study describes the COVID-19 outcomes on a sample of 15 patients with neuromyelitis optica and associated disorders. This included a mix of patients with and without aquaporin-4 and MOG antibodies as well as immunosuppresant treatment. Of the 15 patients, only 5 needed hospitalisation, of which 2 required oxygen and 1 required ICU support. Although the overall outcomes were favourable the authors argue that the 33% hospitalisation rate is relatively high for a young sample and cite immunosuppressive treatments as potentially aggravating factors. These findings should be taken with caution due to the extremely small sample size of this relatively rare condition; but reinforces the need to evaluate the vulnerability of patients with existing neurological conditions to COVID-19.
Publication date / reference: 24/10/2020 Sainz-Amo et al. COVID-19 in Parkinson’s disease: what holds the key? J Neurol.
Summary: The authors of this study compared PD patients with and without covid-19 in order to establish which factors, if any, were related to increased risk of contracting the illness. In summary, there were no PD-specific factors which increased the risk, and only patients who were institutionalised or had malignancy had significantly increased risk. No PD-specific factors were implicated.
Publication date / reference: 13/10/20. Matias -Guiu et al. Death Rate Due to COVID-19 in Alzheimer’s Disease and Frontotemporal Dementia. J Alzheimers Dis.
Summary: An observational study from Spain of patients with Alzheimer’s disease and Frontotemporal dementia (N=24). Authors report a 15.2% enrolled were diagnosed with COVID=19, of which 41.9% died. 72% infections occurred in care homes compared to 7.3% at home. Living in a care home was found to be an independently risk factor of higher infection rate and death. Alzheimer’s disease was found to have a higher mortality rate than frontotemporal dementia, which the authors attributed to higher age and increased incidence of hypertension in Alzheimer patients.
Publication date / reference: 13/10/20. Martin-Jimenez et al.Cognitive Impairment Is a Common Comorbidity in Deceased COVID-19 Patients: A Hospital-Based Retrospective Cohort Study. J Alzheimers Dis.
Summary: Cohort study of deceased COVID-19 patients at a tertiary hospital in Spain (N=477). The study found dementia (21.2%) and mild cognitive impairment (8.9%) was a common comorbidity in this cohort of patients. Authors found this cohort of patients are more likely to live in nursing homes, had shorter time from symptoms onset to death and rarely admitted to ICU.
Publication date / reference: 16/10/20. Perera et al. COVID-19 deaths in people with intellectual disability in the UK and Ireland: descriptive study. BJPsych Open.
Summary: Observational descriptive case series of death due to COVID-19 in people with intellectual disability (N=66). The authors identified that this cohort of patients were younger (mean age 64) compared to the general population. These patients also had higher rates of physical health comorbidities, as well as epilepsy, mental illness, dysphagia, down syndrome and dementia. Almost 80% of the cases (n=55) lived in supported living, residential or care homes. The study highlights the possible higher mortality risk associated with people with intellectual disability. However due to a lack of randomised selection process caution should be taken when making direct inference relating to associated risk factors.
Publication date / reference. 14/10/2020. Dhont et al. Myotonic dystrophy type 1 as a major risk factor for server Covid-19?, Acta Neurol Belg.
Summary: The authors make the case that patients with Steinert’s disease are at high risk of poor Covid-19 outcome, by reporting three cases of hospitalised patients with Steinert’s disease, who all eventually died due to Covid-19.
Publication date / reference: 05/10/2020 Livingston et al. Prevalence, management, and outcomes of SARS-CoV-2 infections in older people and those with dementia in mental health wards in London, UK: a retrospective observational study. Lancet Psychiatry
Summary: This multicenter retrospective study looked at the outcomes of 344 inpatients across 5 greater manchester mental health trusts who were over 65 or had dementia during March-April 2020. 38% were diagnosed with COVID-19 during the study period. Over 90% had physical health comorbidities and 15% of those diagnosed ultimately died of COVID-19. The authors speculate based on these results that patients in psychiatric inpatient settings who were admitted without known SARS-CoV-2 infection had a high risk of infection with SARS-CoV-2 compared with those in the community and therefore parity of esteem is required in mental health and physical health settings. Although this is useful work in a vulnerable cohort, it is worth noting that the data was collected at the very beginning of the pandemic and more up-to-date comparisons on COVID-19 rates and mortality between physical and mental health settings is required.
Publication date / reference: 19/09/2020 Chaudhry et al. COVID-19 in multiple sclerosis patients and risk factors for severe infection. J Neurol Sci.
Summary: Multicenter prospective cohort study looking at the outcomes of 40 MS patients with confirmed COVID-19. MS patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive phenotype, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.
Publication date / reference: 30/9/2020. Li et al. Association of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection. JAMA Netw Open.
Summary: Retrospective cohort study assessing mortality among COVID-19 patients with prior psychiatric diagnoses. They analysed 1685 patients between February 15th 2020 to April 25th 2020 and followed up to May 27th 2020. 473 had prior psychiatric diagnoses. They found that there was a higher mortality rate among the psychiatric cohort compared to those without a prior psychiatric diagnosis, which remained even after controlling for variables.
Publication date / reference: 6/10/2020. Thompson Jr et al. An Epidemiologic Study of COVID-19 Patients in a State Psychiatric Hospital: High Penetrance With Early CDC Guidelines. Psychiatr Serv.
Summary: A study looking at the rate of transmission of SARS-CoV-2 within an inpatient psychiatric setting. It showed that despite following CDC guidelines 51/65 individuals tested positive after the first positive patient was identified. 14/16 asymptomatic individuals housed in the same building tested positive while only 6/51 asymptomatic individuals were positive in the rest of the hospital. States that despite guidelines a high number of patients can become positive and routine wearing of masks prior to identification is warranted.
Publication date / reference: 6/10/2020 Wen et al. Clinical Risk Factors for COVID-19 Among People With Substance Use Disorders. Psychiatr Serv.
Summary: Compared non-elderly (defined as <65) opioid or methamphetamine use disorder against other types of substance use disorder and no substance use disorder. They found that opioid or methamphetamine use disorder correlated with a higher likelihood of having an underlying health condition that increases risk of severe illness in COVID-19 compared to other types and no substance use disorder. Highlights the need for additional support in this cohort.
Publication date / reference: Sept 2020 John et al. Clinical characteristics and admission patterns of stroke patients during the COVID 19 pandemic: A single center retrospective, observational study from the Abu Dhabi, United Arab Emirates. Clin Neurol Neurosurg.
Summary: This was a single centre retrospective observational study comparing hemorrhagic stroke patients with COVID-19 to non-COVID patients admitted. Patients were included with a primary diagnosis of acute ischemic or hemorrhagic stroke.Total number of patients with stroke (n=210), of these, 31 (5.24%) patients with stroke including 19 with ischemic (3.21%) and 12 with hemorrhagic stroke (2.03%) were identified.Comparison was also made with the numbers of stroke patients admitted to the centre in the same period in 2019. Findings were that COVID patients with associated stroke were often male (90.32%), younger, had less vascular RFs. Headache was reported in approximately half of these patients. Limitations include small sample from a single centre and possible selection bias.
Publication date / reference: 01/10/20. Alvarez et al. Risk of SARS-CoV-2 infection and clinical outcomes in multiple sclerosis patients in La Rioja (Spain): [[es]]Riesgo de infección por SARS-CoV-2 y resultados clínicos en pacientes con Esclerosis Múltiple en la Rioja (España). Med Clin (Engl Ed).
Summary: In this retrospective case notes review, Alvarez and colleagues, reviewed the medical records of patients with multiple-sclerosis in the community of La Rioja. 12 patients has been diagnosed with COVID-19. The cumulative hospitalisation rate for patients with MS was 22.2% compared to 36.63% in La Rioja overall. One of the patients with MS and COVID-19 had died.
Publication date / reference: 24/09/20. Al-Hashel & Ismail. Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study. J Headache Pain.
Publication date / reference: 01/09/20. Di Gennaro et al. SARS-CoV-2 Transmission and Outcome in Neuro-rehabilitation Patients Hospitalized at Neuroscience Hospital in Italy. Mediterr J Hematol Infect Dis.
Publication date / reference: 12/09/20. Monaco et al. An educational case series of Parkinson’s disease during the COVID-19 pandemic. Rev Neurol (Paris).
Publication date / reference: 15/09/20. Maguire et al. Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection. J Transl Med.
Summary: In this retrospective cross-sectional study, the authors aimed to elucidate prognostic factors amongst patients admitted to a tertiary centre with COVID-19 during the initial period of the pandemic (n=224, PCR positive in 122). The 30-day mortality was 23%, most often due to respiratory failure and multiorgan failure. The following expected factors were associated with mortality including age (<70), hypertension, heart failure and clinical frailty score. However, of relevance to neurology and neuropsychiatry, a past medical history of cognitive impairment and delirium were significant prognostic factors. These were found in 30/224 and 16/224 patients, respectively. Additionally, delirium was detected in 26/224 patients at presentation, however, the cognitive premorbid state of these patients was not disclosed.
Publication date / reference: 15/09/20. Maguire et al. Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection. J Transl Med.
Summary: In this retrospective cross-sectional study, the authors aimed to elucidate prognostic factors amongst patients admitted to a tertiary centre with COVID-19 during the initial period of the pandemic (n=224, PCR positive in 122). The 30-day mortality was 23%, most often due to respiratory failure and multiorgan failure. The following expected factors were associated with mortality including age (<70), hypertension, heart failure and clinical frailty score. However, of relevance to neurology and neuropsychiatry, a past medical history of cognitive impairment and delirium were significant prognostic factors. These were found in 30/224 and 16/224 patients, respectively. Additionally, delirium was detected in 26/224 patients at presentation, however, the cognitive premorbid state of these patients was not disclosed.
Publication date / reference: 14/09/20. Mirmosayyeb et al. Screening neuromyelitis optica patients for COVID-19 infection. Autoimmune Rev.
Summary: The authors report a survey of 157 patients with NMO, of which six had clinically confirmed COVID-19, with one patient requiring ITU admission.
Publication date / reference: 11/09/20. Nollace et al. Autism and COVID-19: A Case Series in a Neurodevelopmental Unit. J Clin Med.
Summary: This is a case series of patients in a neurobehavioural unit with autism who developed COVID-19. During the pandemic, the neurobehavioural unit was redesigned to provide medical and behavioural care to meet the specific demands of these patients. 11/16 of the patients on the ward had PCR-confirmed COVID-19. The majority of COVID-19 symptoms were similar to the background population, however, five patients developed atypical behaviours which were interpreted as idiosyncratic manifestations, including irrepressible licking behaviour. The patients followed an uncomplicated disease course, including two who were on immunosuppressive therapy.
Publication date / reference: 03/09/20. Maillart et al. Beyond COVID-19: Do MS/NMO-SD patients treated with anti-CD20 therapies develop SARS-CoV2 antibodies? Mult Scler Relat Disord.
Summary: The authors of this case series study included 13 patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) with confirmed COVID-19. In 5 patients treated with anti-CD20 antibodies, SARS-CoV-2 serology was noted to be negative, with median delay between last administration of anti-CD20 treatment and serology being 124 days. The authors go on to mention in discussion that until longer-term longitudinal studies are carried out, individuals should continue to employ maximal precautions to prevent SARS-CoV-2 infection in patients with MS or NMOSD.
Publication date / reference: 30/08/20. Fond et al. Increased in-hospital mortality from COVID-19 in patients with schizophrenia. Encephale.
Summary: This large cohort study examined mortality rates in inpatients with COVID-19 and schizophrenia compared to those without schizophrenia. 1092 patients were included, 15 of which had schizophrenia. The patients with schizophrenia were more likely to be smokers and have cancers as well as respiratory comorbidities than controls. The overall in-hospital mortality rate was 9.0% and schizophrenia patients had an increased mortality compared to non-schizophrenia patients (26.7% vs 8.7% p=0.039) after adjustment for age, sex, smoking status, obesity and Charlson Comorbidity Index. Patients with schizophrenia were not more often admitted to ITU than those without; however, none of the patients with schizophrenia who died were admitted to the ITU, raising questions about advanced age and comorbidities. One major finding of the qualitative analysis was that around two-thirds of the schizophrenia patients were institutionalised, and 100% of them died. Therefore the authors hypothesised that institutionalisation was a risk factor for severe SARS-CoV-2 infection in elderly patients with schizophrenia. One major limitation was the very small (n=15) sample size.
Publication date / reference: 03/09/20. Del Prete et al. Prevalence and impact of COVID-19 in Parkinson’s disease: evidence from a multi-center survey in Tuscany region. J Neurol.
Summary: The authors conducted a prospective case control study to evaluate the prevalence, and impact of COVID-19 in 740 patients with Parkinson’s Disease in Tuscany. From this large cohort only seven patients had confirmed COVID-19; one died. The authors conclude that it remains unclear whether PD is a risk factor for adverse outcome after COVID-19.
Publication date / reference: 03/09/20. Lubansu et al. COVID-19 impact on neurosurgical practice: lockdown attitude and experience of a European academic center. World Neurosurg.
Summary: Although mainly describing lockdown experience, attitudes, and impact on a neurosurgical clinical service (topics that we do not routinely summarise for this blog), the authors report in passing on data from 20 neurosurgical patients found to be positive for SARS-CoV-2, thirteen of whom had been admitted with an acute cerebrovascular event. Seven of nine patients requiring surgical intervention died. Three COVID-19 patients were admitted for a diagnostic biopsy of neoplastic lesions; all three of these patients suffered a critical intracranial hemorrhage and died after these minimally invasive procedures. Regarding these three patients the authors could not exclude simple coincidence, nor a role for neovascularisation unrelated to COVID-19, but neither could they exclude a problematic COVID-19 related haemostatic profile that might result in an unfavorable clinical and surgical outcome.
Publication date / reference: 31/08/20. Mantero et al. Mild COVID‐19 infection in a group of teriflunomide‐treated patients with multiple sclerosis. J Neurol.
Summary: Case series (n=6) of patients with MS treated with teriflunomide who developed ‘self-limiting COVID-19 infection’.The patients were able to continue their therapies and did not experience a relapse of MS. None of the patients required hospitalisation and there were no significant reductions in lymphocytes, neutrophils or leucocytes. The authors caveat that their cohort was marginally younger than similar cohorts described on teriflunomide elsewhere, but conclude that there seems no reason to cease teriflunomide therapy in SARS-CoV-2 infections. To note RT-PCR confirmation of SARS-CoV-2 infection occurred in only three patients, whilst the other three were deemed cases due to symptomatology and exposure.
Publication date / reference: 25/08/20. Onteddu et al. COVID-19 in patients with neurological disorders. Brain Behav Immun Health.
Summary: The authors of this study extracted de-identified data on COVID-19 patients with underlying neurological disorders from TriNetX “COVID-19 Research Network” on July 4th 2020 using ICD-10 codes. A matched control cohort without neurological disorders who were diagnosed with COVID-19 was used for comparisons. In comparisons of 13,166 patients with neurological disorders and 13,166 matched controls, it was found that patients with pre-existing neurological disorders were more likely to be hospitalised, admitted to ICU, be intubated, and had a higher mortality. Subgroup analysis demonstrated higher ITU admission in patients with previous strokes, higher intubation risk in neuromuscular and sleep disorders, and higher mortality in neurodegenerative disorders.
Publication date / reference: 27/08/20. Evangelou et al. Self-diagnosed COVID-19 in people with multiple sclerosis: a community-based cohort of the UK MS register. J Neurol Neurosurg Psychiatry.
Summary: This is an ongoing community based study with self-reported COVID-19 in MS patients (n=3910). Findings suggest that MS patients on immunomodulatory treatments did not have increased risk of COVID-19. Younger age was found to be associated with confirmed or self-diagnosed disease.
Publication date / reference: 11/08/20. Krass et al. COVID-19 Outbreak Among Adolescents at an Inpatient Behavioral Health Hospital. J Adolesc Health
Summary: The authors describe a COVID-19 outbreak among 19 PCR-confirmed adolescent patients at a young people’s psychiatric hospital in the US. Infected patients’ psychiatric diagnoses were most often PTSD, disruptive mood dysregulation disorder, ADHD, MDD, and oppositional defiant disorder. The most common initial symptoms of COVID-19 were sore throat, nausea/vomiting, and cough. Only one patient presented with fever and four were asymptomatic. All recovered: as the authors state, “Depression and anxiety symptoms were noted to escalate early in the disease course. Externalizing behaviors increased as physical health improved.”
Publication date / reference: 14/08/20. Li et al. Resilience of Alzheimer’s Disease to COVID-19. J Alzheimers Dis.
Summary: The authors report a retrospective case note review of clinical characteristics of 19 patients with COVID-19 pneumonia and Alzheimer’s disease (AD), compared to 23 COVID-19 patients without AD. Severity of pneumonia was not significantly different. The median duration from symptom onset to hospitalization, and the duration from hospitalization to discharge, was shorter in AD patients than non-AD patients. The authors conclude that AD patients had a better prognosis, however, several other factors could skew this result including the small sample sizes and the possibility that relatives of AD patients had a higher index of suspicion to refer early, perhaps ameliorating symptoms better with earlier hospital care. (Reviewed from abstract only).
Publication date / reference: 10/08/20. Kummer et al. History of Stroke Is Independently Associated With In-Hospital Death in Patients With COVID-19. Stroke.
Summary: The authors asked whether history of stroke was associated with in-hospital death among patients hospitalized with COVID-19. Using institutional electronic health records they identified 3248 COVID-19 patients admitted to five hospitals in the New York area, 387 of whom had a prior history of stroke. Patients with a history of stroke were significantly more likely to die during their hospitalization than those without (48.6% versus 31.7%). The effect remained significant after adjusting for age and 12 medical comorbidities. The authors speculate that higher frailty, frequency of advance directives such as do-not-resuscitate orders, or reluctance to escalate to ICU care may explain some of the result. They acknowledge limitations including the retrospective nature, lack of medication data or information on type of historical stroke. They call for larger cohort sizes and more granular patient-level data in future studies.
Publication date / reference: 27/07/20. Diagnosing myasthenic crisis in SARS-CoV-2 infected patients requires adherence to appropriate criteria. J Neurol Sci.
Summary: Correspondence on the report by Delly et al. claiming the first myasthenic crisis in SARS-CoV-2 infection. The authors feel the original report has several limitations and that in future studies should give more detailed evidence from biochemistry and validated scoring systems before attributing respiratory failure in SARS-CoV-2 to a relapse of MG.
Publication date / reference: 04/08/20. Romagnolo et al. Neurological comorbidity and severity of COVID-19. J Neurol.
Summary: The authors of this study consecutively recruited 344 COVID-19 patients and recorded data on neurological and non-neurological comorbidities as well as COVID-19 disease severity. Neurological comorbidities were seen in 22.4% of cases, with pre-existing cerebrovascular disease and cognitive impairment being most common. Neurological comorbidities were seen to be independently associated with severe COVID-19, though they were also associated with male gender, older age, neoplastic disease and arterial hypertension. Neurological comorbidities were also associated with a greater rate of non-invasive mechanical respiratory support and intensive care requirement.
Publication date / reference: 28/7/2020. Han et al. Inpatients with brain damage, impaired airways and severely restricted daily activities have an increased infection rate during the COVID-19 pandemic: a single-center retrospective analysis from Wuhan. Am J Phys Med Rehabil.
Summary: In this retrospective case series, Han and colleagues analysed the clinical features of patients with brain injury with COVID-19 (PCR confirmed) on a single rehabilitation ward (n=4). All patients first presented with fever, three had a cough and one had dyspnoea. Only one patient had a significant increase in WBC and neutrophil count. One patient died within a week of diagnosis, two patients were severely infected and one was mildly infected. In all patients, typical changes were not seen on CT; Han and colleagues theorised that this may be due to underlying pulmonary infection or evidence of previous infections on CT. The authors speculated that patients with brain injury may be more susceptible to SARS-Cov-2 infection for reasons including airway impairment, low activity level and frequent contact with caregivers. This study is limited by its small sample size recruited from a single ward.
Publication date / reference: Yanover et al. What factors increase the risk of complications in SARS-Cov-2 infected patients? A cohort study in a nationwide Israeli health organization. JMIR Public Health Surveill.
Summary: In this retrospective cohort study, Yanover and colleagues sought to identify factors associated with COVID-19 complications by retrospectively analysing the complete medical records from a nationwide health organisation. The prevalence of COVID-19 complications in this infected cohort was 4% (173/4353, PCR-confirmed), defined as moderate-severe disease or requiring ICU. As expected, prior cardiovascular disease and diabetes were significant risk factors for COVID-19 complications. Interestingly, depression, neurological disorders and cognitive impairment were also significant risk factors. The accuracy of these results are somewhat doubted by the surprising finding that smoking and prior respiratory disease did not significantly increase risk of COVID-19 complications. The findings were also limited by the retrospective nature of the study and reliance on diagnostic codes in medical records.
Publication date / reference: 22/07/20. Rein et al. Description of 3 patients with myasthenia gravis and COVID-19. J Neurol Sci.
Summary: This is a case series of three patients with generalised seropositive myasthenia gravis (MG) who developed COVID-19. Despite all three patients being on immunosuppressive therapy for their MG (including IVIg and prednisolone), all had positive outcomes. One patient developed severe COVID-19 disease, requiring mechanical ventilation and experienced a MG exacerbation. However, this patient recovered well despite treatment with hydroxychloroquine, lopinavir and ritonavir. The other two patients had an uncomplicated course of illness. Rein and colleagues suggest that these findings could indicate that immunosuppressive therapy is safe to continue in MG patients with COVID-19, although this needs to be validated in a larger cohort.
Publication date / reference: 07/07/2020. García-Azorín et al. Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients. Front Neurol.
Summary: In this single-site study the authors looked to assess predictors of mortality in COVID-19 patients. To achieve this, they used a retrospective notes review design with a primary endpoint of mortality, comparing those with pre-existing neurological disorders (n = 105) to those without (n = 471). Presence of a pre-existing neurological disorder was an independent predictor of death (HR 2.1) but not a more severe COVID-19 presentation (OR: 1.75 [n.s.]). The latter was defined according to the American Thoracic Society guidelines for community-acquired pneumonia.
Publication date / reference: 19/07/20. Mallucci et al. Asymptomatic SARS-CoV-2 infection in two patients with multiple sclerosis treated with fingolimod. Mult Scler Relat Disord.
Summary: Two patients with multiple sclerosis on fingolimod treatment who subsequently tested positive for SARS-CoV-2. Both survived, suggesting fingolimod, a disease-modifying treatment, does not seem to expose individuals to an unfavourable COVID-19 evolution, and may in fact be protective.
Publication date / reference: 17/07/20. Fernández-Díaz et al. COVID-19 and multiple sclerosis: A description of two cases on alemtuzumab. Mult Scler Relat Disord.
Summary: Two young patients with multiple sclerosis developed COVID-19. Both were treated previously with alemtuzumab, one in the week before infection. Both fully recovered, indicating disease-modifying treatments in MS may be safe to continue during the COVID-19 pandemic.
Publication date / reference: 12/07/20. Ciampi et al. COVID-19 in MS and NMOSD: A multicentric online national survey in Chile. Mult Scler Relat Disord.
Summary: In this correspondence, Ciampi and colleagues described the results from an online questionnaire administered to their patients with MS and Neuromyelitis Optica Spectrum Disorders (NMOSD) to determine the impact of COVID-19 on this cohort. Of the 409 patients who completed the survey, 18 (4.4%) self-reported COVID-19, 14 of whom had relapsing remitting disease and four with NMOSD. All of the patients were on immunotherapy. Similar to previous reports, the majority of patients (13/18) did not require hospitalisation, whilst one patient with severe illness developed critical illness polyneuromyopathy and had a fatal outcome. Although the results of this study are potentially reassuring for patients with MS, they are limited by the sample size and selection approach which may be less sensitive at including people with severe COVID-19.
Publication date / reference: 19/10/2020 Pensato et al., Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke. Front Neurol.
Publication date / reference: 07/11/2020 Boostani et al., COVID-19 associated with sensorimotor polyradiculoneuropathy and skin lesions: A case report. J Neuroimmunol.
Publication date / reference: 15/10/2020 Han et al., Delirium During Recovery in Patients With Severe COVID-19: Two Case Reports. Front Med (Lausanne)
Publication date / reference: Fall, 2020 Nateghian and Anvari Partial seizure due to COVID19 infection in an infant. Iran J Child Neurol
Publication date / reference: 27/08/2020 Atakla et al., Acute Guillain-Barré polyradiculoneuritis indicative of COVID-19 infection: a case report. Pan Afr Med J.
Publication date / reference: 11/11/2020 Othenin-Girard et al. Multisystem inflammatory syndrome with refractory cardiogenic shock due to acute myocarditis and mononeuritis multiplex after SARS-CoV-2 infection in an adult. Swiss Med Wkly.
Publication date / reference: 11/11/2020 Yousefi et al. Viral Meningitis Associated With covid-19 in a 9-year-old Child: A Case Report. Pediatr Infect Dis J.
Publication date / reference: 10/11/20 Mitry et al. Parsonage-turner syndrome associated with SARS-CoV2 (COVID-19) infection. Clin Imaging.
Publication date / reference: 01/11/20. Freire-Álvarez et al. COVID-19-associated encephalitis successfully treated with combination therapy. Clin Infect Pract.
Publication date / reference: 2/11/2020 Wright et al. Abnormal Saccadic Oscillations Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Encephalopathy and Ataxia. Mov Disord Clin Pract
Publication date / reference: 15/10/2020. Saud Bin Abdul Sattar et al. Locked-in Syndrome in a Young Patient Due to SARS-CoV-2: A Case Report. Front Med.
Publication date / reference: 08/09/20 Schellekens et al. Reversible myoclonus-ataxia as a postinfectious manifestation of COVID-19. Mov Disord Clin Pract.
Publication date / reference: 10/2020 Tard et al. Anti-pan-neurofascin IgM in COVID-19-related Guillain-Barré syndrome: Evidence for a nodo-paranodopathy. Neurophysiol Clin.
Publication date / reference: 05/10/2020. Flores et al., Spontaneous Brainstem Hemorrhagic Stroke in the Setting of Novel Coronavirus Disease 2019 – A Case Report. Cureus.
Publication date / reference: 21/12/2020. Kataria et al. A case series and literature review of multiple sclerosis and COVID-19: Clinical characteristics, outcomes and a brief review of immunotherapies. eNeurologicalSci.
Publication date / reference: 20/10/2020. Hayat et al. Encephalopathy as the Presenting Symptom of COVID-19. Kans J Med.
Publication date / reference: 22/08/2020. Pavlov et al. COVID-19-Related Intracerebral Hemorrhage. Front Aging Neurosci.
Publication date / reference: 05/11/20 Casez et al. SARS-CoV-2 Related Encephalitis: MRI Pattern of the Olfactory Tract Involvement. Neurology.
Publication date / reference: 02/11/20. Affes et al. COVID-19 Presenting With Confusion: An Unusual but Suggestive Electroencephalography Pattern of Encephalitis. J Clin Neurophysiol.
Publication date / reference: 05/09/2020. Sattar et al. Clinical, Radiological, and Molecular Findings of Acute Encephalitis in a COVID-19 Patient: A Rare Case Report. Cureus.
Publication date / reference: 08/2020. Papa et al. Clinical Management of Il-6 Driven Cytokine Storm Related to COVID-19 in a Patient with Recent Spinal Cord Stimulator Implants: A Case Report. Anesth Pain Med.
Publication date / reference: 3/10/20 Haider et al. COVID-19 and the Brain: Acute Encephalitis as a Clinical Manifestation. Cureus.
Publication date / reference: 30/10/20 Urciuoli et al. ACUTE ISCHEMIC AND HEMORRHAGIC STROKE IN TWO COVID-19 PATIENTS. Jpn J Infect Dis.
Publication date / reference: 5/11/20 de Castillo et al. Concurrent Acute Ischemic Stroke and Non-aneurysmal Subarachnoid Hemorrhage in COVID-19. Can J Neurol Sci.
Publication date / reference: 3/11/2020. Fedele Dono et al. New-onset refractory status epilepticus (NORSE) in post SARS-CoV-2 autoimmune encephalitis: a case report. Neurol Sci.
Publication Date/Reference: 29/10/2020 Asif et al. Rare complication of COVID-19 presenting as isolated headache. BMJ Case Rep.
Publication Date/Reference: 31/01/2020 Khaja et al. A 44-Year-Old Hispanic Man with Loss of Taste and Bilateral Facial Weakness Diagnosed with Guillain-Barré Syndrome and Bell’s Palsy Associated with SARS-CoV-2 Infection Treated with Intravenous Immunoglobulin. Am J Case Rep.
Publication Date/Reference: 28/10/2020 Moghadasi. Encephalopathy associated with COVID-19 in a patient with multiple sclerosis. J Neurovirol.
Publication Date/Reference: 27/10/2020. Panico et al. Balint-Holmes syndrome due to stroke following SARS-CoV-2 infection: a single-case report. Neurol Sci.
Publication Date/Reference: 26/10/2020. de Freitas Ribeiro & Marchiori. Facial palsy as a neurological complication of SARS-CoV-2. Arq Neuropsiquiatr.
Publication Date/Reference: 06/10/2020. Huber et al. Postinfectious Onset of Myasthenia Gravis in a COVID-19 Patient. Front Neurol.
Publication Date/Reference: 30/9/2020 Águila-Gordo et al. Acute myelitis and SARS-CoV-2 infection. A new etiology of myelitis? J Clin Neurosci.
Publication Date/Reference: 20/09/2020 George et al. To Anticoagulate or Not: Acute Stroke in a COVID-19 Patient With Gastrointestinal Bleed. Cureus.
Publication Date/Reference: 25/09/2020 Efendizade et al. Unfractionated Heparin in SARS-CoV-2 Pneumonia: Ischemic Stroke Case Report. Front Neurol.
Publication Date/Reference: 01/10/2020 Abbaslou et al. A Rare Axonal Variant of Guillain-Barré Syndrome as a Neurological Complication of COVID-19 Infection. Arch Iran Med.
Publication date / reference: Nov, 2020 Patel et al. Malignant Cerebral Ischemia in A COVID-19 Infected Patient: Case Review and Histopathological Findings J Stroke Cerebrovasc Dis
Publication date / reference: 22/10/2020 Curtis et al. Guillain-Barré Syndrome in a Child With COVID-19 Infection. Paediatrics.
Publication date / reference: 15/10/2020. Belghmaidi et al. Third Cranial Nerve Palsy Presenting with Unilateral Diplopia and Strabismus in a 24-Year-Old Woman with COVID-19 Am J Case Rep.
Publication date / reference: 16/10/2020 Pessoa Neto et al. Possible acute multifocal demyelinating lesions in a COVID-19 patient. Arq. Neuro-Psiquiatr.
Publication date / reference: 16/10/20. Karapanayiotides et al. Concentric demyelination pattern in COVID-19-associated acute hemorrhagic leukoencephalitis: a lurking catastrophe? Brain.
Publication date / reference: 10/09/20. Wijeratne et al. First Australian case of good recovery of a COVID-19 patient with severe neurological symptoms post prolonged hospitalization. Cureus.
Publication date / reference: 04/07/20. Hussain et al. A Case of Coronavirus Disease 2019 Presenting with Seizures Secondary to Cerebral Venous Sinus Thrombosis. Case Rep Neurol
Publication date / reference: 20/07/2020. Weidauer et al. Juvenile Embolic Stroke Complicating COVID-19 Infection. Dtsch Arztebl Int.
Publication date / reference: 09/20. Kakadia et al. Mild encephalopathy with reversible splenium lesion (MERS) in a patient with COVID-19. J Clin Neurosci.
Publication date / reference: 09/20. Thu et al. Olfactory gyrus intracerebral hemorrhage in a patient with COVID-19 infection. J Clin Neurosci.
Publication date / reference: 09/20. Sugiyama et al. Cerebral venous thrombosis in COVID-19-associated coagulopathy: A case report. J Clin Neurosci.
Publication date / reference: 09/20. Vaschetto et al. Cerebral nervous system vasculitis in a Covid-19 patient with pneumonia. J Clin Neurosci.
Publication date / reference: 22/10/20. Borroni et al. Diaphragmatic myoclonus due to SARS-CoV-2 infection. Neurol Sci.
Publication date / reference: 22/10/20. Agarwal et al. Serial Imaging of Virus-Associated Necrotizing Disseminated Acute Leukoencephalopathy (VANDAL) in COVID-19
Publication date / reference: 13/10/20. Fitzpatrick et al. Cranial Nerve III Palsy in the setting of COVID 19 Infection. J Neuroophthalmol.
Publication date / reference: 15/10/20. Chia et al. Possible affective cognitive cerebellar syndrome in a young patient with COVID-19 CNS vasculopathy and stroke. BMJ Case Rep.
Publication Date/Reference: 14/10/2020. Christopher Green et al. Teaching Neuroimages: COVID-19 associated acute disseminated encephalomyelitis with corpus callosal hemorrhage. Neurology.
Publication date / reference: 06/09/20. Rascon-Ramirez et al. Supra and infratentorial massive strokes in previously healthy young patients with SARS-CoV-2. The role of neurosurgery. Neurocirugia (Astur).
Publication date / reference: 10/10/20. Dakay et al. Cerebral Herniation Secondary to Stroke-Associated Hemorrhagic Transformation, Fulminant Cerebral Edema in Setting of COVID-19 Associated ARDS and Active Malignancy. J Stroke Cerebrovasc Dis.
Publication date / reference: 10/10/20. Crippa et al. Stroke in a young adult with mild COVID-19 suggesting endotheliitis. New Microbes New Infect.
Publication date / reference: 13/10/20. Bektaş et al. Reversible splenial lesion syndrome associated with SARS-CoV-2 infection in two children. Brain Dev.
Publication date / reference: 14/10/2020 Casciato et al. New-onset anosmia and taste distortion: see beyond COVID-19. Neurol Sci.
Publication date / reference: 12/10/20. Sriwastava et al. New onset of ocular myasthenia gravis in a patient with COVID-19: a novel case report and literature review. J Neurol.
Publication date / reference: 04/10/20. Chee Chow et al. Thrombosis and Bleeding as Presentation of COVID-19 Infection with Polycythemia Vera. A Case Report. SN Compr Clin Med.
Publication date / reference: 08/09/2020 Farooque et al. Coronavirus Disease 2019-Related Acute Ischemic Stroke: A Case Report. Cureus.
Publication date / reference: 26/09/20. Sripadma P V et al. Postpartum Atypical Posterior Reversible Encephalopathy Syndrome in a COVID-19 Patient – An Obstetric Emergency. J Stroke Cerebrovasc Dis.
Publication date / reference: 09/09/20. Allen et al. Neuraxial anaesthesia in the context of bacteria meningitis and COVID-19. Br J Anaesth.
Publication date / reference: 03/09/20. Ashraf et al. Acute Stroke in a Young Patient With Coronavirus Disease 2019 in the Presence of Patent Foramen Ovale. Cureus.
Publication date / reference: 04/08/20. Defabio et al. Guillain-Barré syndrome in a patient previously diagnosed with COVID-19.Am J Emerg Med.
Publication date / reference: 12/10/20. Fontanella et al. Comment about the article “SARS-CoV-2 can induce brain and spine demyelinating lesions,” Acta Neurochir (Wien) 2020 Jul;162(7):1491-1494. Acta Neurochir (Wien).
Publication date / reference: 25/09/20. Mowla et al. Unusual Pattern of Arterial Macrothrombosis Causing Stroke in a Young Adult Recovered from COVID-19. J Stroke Cerebrovasc Dis.
Publication date / reference: 09/10/2020 Saitta et al. Brain microvascular occlusive disorder in COVID-19: a case report. Neurol Sci.
Publication date/ reference: 06/10/2020 Rodriguez et al. SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report. BMC Pregnancy Childbirth.
Publication date / reference: Dec 2020. Novak. Post COVID-19 syndrome associated with orthostatic cerebral hypoperfusion syndrome, small fiber neuropathy and benefit of immunotherapy: a case report. eNeurologicalSci.
Publication date / reference: 06/10/20. Zhang et al. COVID-19-Associated Acute Multi-infarct Encephalopathy in an Asymptomatic CADASIL Patient. Neurocrit Care.
Publication date / reference: 06/10/20. Ortiz-Seller et al. Ophthalmic and Neuro-ophthalmic Manifestations of Coronavirus Disease 2019 (COVID-19). Ocul Immunol Inflamm.
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Publication date / reference: 01/10/20. Ho et al. Case report of familial COVID-19 cluster associated with high prevalence of anosmia, ageusia, and gastrointestinal symptoms. IDCases.
Publication date / reference: Oct 2020. Naraayaan et al Severe Hyponatremic Encephalopathy in a Patient With COVID-19 Mayo Clin Proc
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Publication date / reference: Oct 2020. Mantero et al. Stroke in a Feverish Patient with COVID-19 Infection and Unknown Endocarditis. J Clin Neurol.
Publication date/ reference: 1/10/20. Henriques-Souza et al. Acute disseminated encephalomyelitis in a COVID-19 pediatric patient. Neuroradiology.
Publication date / reference: 30/09/2020. García-Manzanedo et al. Guillain-Barré syndrome after Covid-19 infection. Med Clin (Engl Ed).
Publication date / reference: 30/09/20. Cabrera Muras et al. Bilateral Facial Nerve Palsy associated with COVID-19 and Epstein-Barr Virus co-infection. Eur J Neurol
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Publication date / reference: Jan-Dec 2020. Rajdev et al. A Case of Guillain-Barré Syndrome Associated With COVID-19. J Investig Med High Impact Case Rep.
Publication date / reference: 04/10/20. Chauffier et al. First Case of Mild Encephalopathy with Reversible Splenial Lesion in SARS-CoV-2 Infection. Med Mal Infect. This interesting case report described a 47-year-old previously well man who presented to the emergency department with acute onset confusion. The patient had a range of nervous system abnormalities including cognitive dysfunction, inattention, psychomotor slowness, confabulations and logorrhoea, amongst others. This was in the background of a two-week history of dry cough and headache. Brain MRI revealed a lesion confined to the splenium of the corpus callosum. The patient rapidly improved and required only oxygen therapy, will full recovery after 7 days. The authors hypothesised mild encephalopathy with reversible splenial lesion of vascular origin as the potential aetiology.
Publication date / reference: 08/10/20. Lim et al. Spontaneous Epidural Hematoma of the Cervical Spine in an Elderly Woman with Recent COVID-19 Infection: A Case Report. Am J Case Rep.
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Publication date / reference: 06/10/20. Prasad et al. Multiple embolic stroke on magnetic resonance imaging of the brain in a COVID-19 case with persistent encephalopathy. Clin Imaging.
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Publication date / reference: 24/09/20. Mansour et al. Mechanical Thrombectomy of COVID-19 positive acute ischemic stroke patient: a case report and call for preparedness. BMC Neurol.
Publication date / reference: 24/09/20. Roussel et al. Cranial polyneuropathy as the first manifestation of a severe COVID-19 in a child. Pediatr Blood Cancer.
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Publication date / reference: 21/08/20. Bhagat et al. A Case of Isolated Dysarthria in a COVID-19 Infected Stroke Patient: A Nondisabling Neurological Symptom With Grave Prognosis. Cureus.
Publication date / reference: 23/09/20. Demir et al. Fahr’s syndrome presenting with seizures in SARS-CoV-2 (COVID-19) pneumonia-a case report. Neurol Sci.
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Publication date / reference: 17/09/20. Masuccio et al. A rare case of acute motor axonal neuropathy and myelitis related to SARS-CoV-2 infection. J Neurol.
Publication date / reference: 10/20. Cohen et al. A case of probable Parkinson’s disease after SARS-CoV-2 infection. Lancet Neurol.
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Publication date / reference: Oct 2020. Shoskes et al. Cerebral Microhemorrhage and Purpuric Rash in COVID-19: The Case for a Secondary Microangiopathy. J Stroke Cerebrovasc Dis.
Publication date / reference: Oct 2020. Trifan et al. Acute Stroke as the Presenting Symptom of SARS-CoV-2 Infection in a Young Patient with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. J Stroke Cerebrovasc Dis.
Publication date / reference: Oct 2020. Patel et al. “COVID-19 and cervical artery dissection- A causative association?” J Stroke Cerbrovasc Dis.
Publication date / reference: 18/09/20. Baghbanian & Namazi. Post COVID-19 longitudinally extensive transverse myelitis (LETM)-a case report. Acta Neurol Belg.
Publication date / reference: 18/09/20. Carroll et al. Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus. Epilepsia.
Publication date / reference: 17/09/20. Ayatollahi et al. Possible autoimmune encephalitis with claustrum sign in case of acute SARS-CoV-2 infection. Can J Neurol Sci.
Publication date / reference: 17/09/20. Cavalagli et al. Cranial nerves impairment in post-acute oropharyngeal dysphagia after COVID-19: a case report. Eur J Phys Rehabil Med.
Publication date / reference: 16/09/20. Kamal et al. Cerebrospinal fluid confirmed COVID-19-associated encephalitis treated successfully. BMJ Case Rep.
Publication date / reference: 15/09/20. Nicolas-Jilwan & Almaghrabi. Diffuse necrotising leukoencephalopathy with microhaemorrhages in a patient with severe COVID-19 disease. Neuroradiol J.
Publication date / reference: 15/09/20. Chiu et al. COVID-19-induced anosmia associated with olfactory bulb atrophy. Neuroradiology.
Publication date / reference: 15/09/20. Di Nicola et al. Concomitant SARS-CoV-2 infection and severe neurologic involvement in a late preterm neonate. Neurology.
Publication date / reference: 14/09/20. Essajee et al. Child with tuberculous meningitis and COVID-19 coinfection complicated by extensive cerebral sinus venous thrombosis. BMJ Case Rep.
Publication date / reference: 14/09/20. Ameer et al. Guillain-Barré syndrome presenting with COVID-19 infection. BMJ Case Rep.
Publication date / reference: 14/09/20. Khodamoradi et al. COVID-19 meningitis without pulmonary involvement with positive cerebrospinal fluid PCR. Eur J Neurol.
Publication date / reference: 11/09/20. Ghosh et al. Autonomic dysfunction heralding acute motor axonal neuropathy in COVID-19. J Neurovirol.
Publication date / reference: 11/09/20. Liberatore et al. Clinical Reasoning: A case of COVID-19 associated pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. Neurology.
Publication date / reference: 11/09/20. Chan et al. Pituitary apoplexy associated with acute COVID-19 infection and pregnancy. Pituitary.
Publication date / reference: 10/09/20. Corrêa et al. COVID-19 associated with encephalomyeloradiculitis and positive anti-aquaporin-4 antibodies: Cause or coincidence? Mult Scler. And a commentary to it: Valencia-Sanchez et al. COVID-19 associated with encephalomyeloradiculitis and positive anti-aquaporin-4 antibodies: Cause or coincidence? – Commentary. Mult Scler.
Publication date / reference: 10/09/20. Guadarrama-Ortiz et al. Chronic subclinical spondylotic myelopathy exacerbated by COVID-19: a case report. Interdiscip Neurosurg.
Publication date / reference: 10/09/20. Ordas et al. Concurrent tonic pupil and trochlear nerve palsy in COVID-19. J Neurvirol.
Publication date / reference: 07/09/20. Ghosh et al. Hallucinatory palinopsia in COVID-19 induced posterior reversible encephalopathy syndrome. J Neuroophthalmol.
Publication date / reference: 07/09/20. Sanguinetti & Randhani. Opsoclonus myoclonus ataxia syndrome related to the novel coronavirus (COVID-19). J Neuroophthalmol
Publication date / reference: 29/08/20. Gupta et al. Critical illness-associated cerebral microbleeds in severe COVID-19 infection. Clin Imaging.
Publication date / reference: 26/08/20. Rodrigo-Armenteros et al. Non-convulsive status epilepticus in a patient with COVID-19 infection. Clin Neurophysiol.
Publication date / reference: 13/08/20. Franceschi et al. Incidental PET/CT Findings of Suspected COVID-19 in a Region of High Prevalence. Cureus.
Publication date / reference: 12/08/20. Diez-Porras et al. Guillain-Barré-Strohl syndrome and COVID-19: case report and literature review. Neuromuscul Disord.
Publication date / reference: 08/20. Packwood et al. An unusual case report of COVID-19 presenting with meningitis symptoms and shingles. Clin Pract Cases Emerg Med.
Publication date / reference: 08/20. Klein et al. A case report of coronavirus disease 2019 presenting with tremors and gait disturbance. Clin Pract Cases Emerg Med.
Publication date / reference: 08/20. Ford et al. Cardioembolic stroke in a patient with coronavirus disease of 2019 (COVID-10) myocarditis: a case report. Clin Pract Cases Emerg Med.
Publication date / reference: Aug 2020. Copscik et al. A Case Report of Acute Motor and Sensory Polyneuropathy as the Presenting Symptom of SARS-CoV-2. Clin Pract Cases Emerg Med.
Publication date / reference: 24/07/20. Abdelhady et al. Acute Flaccid Myelitis in COVID-19. BJR Case Rep.
Publication date / reference: 03/07/20. Agarwal et al. Unusual lesion in the splenium of the corpus callosum and coronavirus infectious disease-19. BJR Case Rep.
Publication date/reference: 09/09/20 Freji et al. Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child. BMC Pediatr.
Publication date/reference: 08/09/20 Burkert et al. Acute cerebrovascular event in a COVID-19 positive patient immediately after commencing non-invasive ventilation. BMJ Case Rep.
Publication date/reference: 08/09/20 Etemadifar et al. Fulminant encephalitis as a sole manifestation of COVID-19 Neurol Sci.
Publication date/reference: 08/09/20 Bigliardi et al. Middle cerebral artery ischemic stroke and COVID-19: a case report J Neurovirol.
Publication date / reference: 06/09/20. El-Zein et al. COVID-19-associated meningoencephalitis treated with intravenous immunoglobulin. BMJ Case Rep.
Publication date / reference: 05/09/20. Motoie et al. Coronavirus Disease 2019 Complicated by Multiple Simultaneous Intracerebral Hemorrhages. Intern Med.
Publication date / reference: 03/09/20. Sayeed & Sorafa. Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy; Case report and review the literature. IDCases.
Publication date / reference: 01/09/20. de Ruijter et al. Neuromyelitis optica spectrum disorder after presumed coronavirus (COVID-19) infection: A case report. Mult Scler Relat Disord.
Publication date / reference: 27/08/2020 Lui et al. Prognosis of olfactory and gustatory dysfunctions in COVID-19 patients: A case series. Clin Case Rep.
Publication date / reference: 10/08/20. Ordonez-Boschetti et al. Associated posterior reversible encephalopathy syndrome (PRES) to SARS-CoV-2. Case report. Neurologia.
Publication date / reference: 31/07/20. Pena-Salazar et al. Convulsive status epilepticus as a possible symptom of COVID-19 in a patient with intellectual disability and autistic spectrum disorder. Neurologia.
Publication date / reference: 21/07/20. Abenza-Abildua et al. Myopathy associated with serious SARS-CoV-2 infection. Neurologia.
Publication date / reference: 16/07/20. Barrachina-Esteve et al. Guillain-Barré syndrome as the first manifestation of SARS-CoV-2 infection. Neurologia.
Publication date / reference: 3/09/20. Cassia et al. Fatal stroke as presentation of SARS-CoV-2 and dengue virus coinfection. J Med Virol.
Publication date / reference: 3/09/20. Khan et al. Ischemic stroke leading to bilateral vision loss in COVID-19 patient- A rare case report. J Med Virol.
Publication date / reference: 03/09/20. Miglis et al. A case report of postural tachycardia syndrome after COVID-19. Clin Auton Res.
Publication date / reference: 03/09/20. Ayuso et al. Bickerstaff encephalitis after COVID-19. J Neurol.
Publication date / reference: 03/09/20. Zuhorn et al. Parainfectious encephalitis in COVID-19: “The Claustrum Sign. J Neurol.
Publication date / reference: 02/09/20. Handa et al. Covid-19-associated acute haemorrhagic leukoencephalomyelitis. Neurol Sci.
Publication date / reference: 01/09/20. Sánchez-Soblechero et al. Upper trunk brachial plexopathy as a consequence of prone positioning due to SARS-CoV-2 acute respiratory distress syndrome. Muscle Nerve.
Publication date / reference: 31/08/20. Gogia et al. Intracranial Hemorrhage in a Patient With COVID-19: Possible Explanations and Considerations. Cureus.
Publication date / reference: 28/08/20. Garg et al.A Case of COVID-19 With Memory Impairment and Delayed Presentation as Stroke. Cureus.
Publication date / reference: 26/08/20. Llanso & Ura. Posterior Reversible Encephalopathy Syndrome in COVID-19 Disease: a Case-Report. SN Compr Clin Med.
Publication date / reference: 14/08/20. Wettervik et al. Intracranial Pressure Dynamics and Cerebral Vasomotor Reactivity in Coronavirus Disease 2019 Patient With Acute Encephalitis. Crit Care Explor.
Publication date / reference: 25.08.2020 Gallacher et al. Meningococcal meningitis and COVID-19 co-infection BMJ Case Rep.
Publication date / reference: 29.07.2020 Patel et al. Cerebellar infarction requiring surgical decompression in patient with COVID 19 pathological analysis and brief review Interdiscip Neurosurg.
Publication date / reference: 09/20. Granger et al. SARS-CoV-2-Associated Guillain-Barre Syndrome With Good Response to Plasmapheresis. J Clin Neuromuscul Dis.
Publication date / reference: 17/07/2020 Ros-Castello et al. Post-hypoxic myoclonus after COVID-19 infection recovery Mov Disord Clin Pract.
Publication date / reference: 27/08/20. Renieri. High mortality rate in COVID-19-associated stroke, analysis of risk factors. J Neurol Neurosurg Psychiatry.
Publication date / reference: 28/08/2020 Civardi et al., Antiganglioside antibodies in Guillain-Barré syndrome associated with SARS-CoV-2 infection
Publication date / reference: 03/08/20. Conto-Palomino et al. Encephalitis associated with COVID-19 in a 13-year-old girl: A case report Medwave
Publication date / reference: 14/08/20. Avci et al. Spontaneous subarachnoidal hemorrhage in patients with Covid-19: case report. J Neurovirol.
Publication date / reference: 14/08/20. Basirjafari et al. Association of Pediatric COVID-19 and Subarachnoid Hemorrhage. J Med Virol.
Publication date / reference: 16/08/20. Ghosh et al. SARS-CoV-2-Associated Acute Hemorrhagic, Necrotizing Encephalitis (AHNE) Presenting with Cognitive Impairment in a 44-Year-Old Woman without Comorbidities: A Case Report Am J Case Rep.
Publication date / reference: September 2020. Papi et al. Unprotected stroke management in an undiagnosed case of Severe Acute Respiratory Syndrome Coronavirus 2 infection. J Stroke Cerebrovasc Dis.
Publication date / reference: September 2020. Dakay et al. Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection. J Stroke Cerebrovasc Dis.
Publication date / reference: September 2020. Zahid et al. Hemorrhagic stroke in setting of severe COVID-19 infection requiring Extracorporeal Membrane Oxygenation (ECMO). J Stroke Cerebrovasc Dis.
Publication date / reference: 18/08/20. Moreau et al. Cytotoxic lesions of the corpus callosum (CLOCCS) associated with SARS-CoV-2 infection. J Neurol.
Publication date / reference: 18/08/20. Forestier et al. Cytotoxic lesion of the corpus callosum as presenting neuroradiological manifestation of COVID-2019 infection. J Neurol.
Publication date / reference: 19/08/20. Lima et al. Acute peripheral artery occlusion and ischemic stroke in a patient with COVID-19. Vasc Med.
Publication date / reference: 18/08/2020. Bin Mohamed et al. Massive bilateral stroke in a COVID-19 patient. BMJ Case Rep.
Publication date / reference: 13/08/2020. Conte et al. COVID-19-Associated PRES-like Encephalopathy with Perivascular Gadolinium Enhancement. AJNR Am J Neuroradiol.
Publication date / reference: 19/08/20. Faber et al. Covid-19 and Parkinsonism: A non-post-encephalitic case. Mov Disord.
Publication date / reference:13/08/20. Gulk et al. Vessel Wall Enhancement and Focal Cerebral Arteriopathy in a Pediatric Patient with Acute Infarct and COVID-19 Infection. AJNR Am J Neuroradiol.
Publication date / reference: 14/08/20. Hoang et al. Clinical Reasoning: Therapeutic considerations in myasthenic crisis due to COVID-19 infection. Neurology
Publication date / reference: 28/06/20. Bonardel et al. Bilateral posterior cerebral artery territory infarction in a SARS-CoV-2 infected patient: discussion about an unusual case. J Stroke Cerebrovasc Dis.
Publication date / reference: 31/07/20. Swarz et al. COVID-19 infection presenting as acute-onset focal status epilepticus. Pediatr Neurol.
Publication date / reference: 08/08/20. Pelea et al. SARS-CoV-2 associated Guillain-Barré syndrome. J Neurol.
Publication date / reference: 09/08/20. Maideniuc et al. Acute necrotising myelitis and acute motor axonal neuropathy in a COVID-19 patient. J Neurol.
Publication date / reference: 20/07/20. Abdulsalam et al. Generalized Status Epilepticus as a Possible Manifestation of COVID-19. Acta Neurol Scand.
Publication date / reference: 11/08/20. Senel et al. Miller-Fisher syndrome after COVID-19: neurochemical markers as an early sign of nervous system involvement. Eur J Neurol.
Publication date / reference: 03/07/20. Elkhouly & Kaplan. Noteworthy Neurological Manifestations Associated With COVID-19 Infection. Cureus.
Publication date / reference: 04/20. Janjua & Moscote-Salazar. Acute Cerebellar Strokes with Anoxic Brain Injury After a Cardiopulmonary Arrest in SARS-CoV-2 Patient. Acta Med Indones.
Publication date / reference: 10/08/20. Aksan et al. A COVID-19 patient with intense burning pain. J Neurovirol.
Publication date / reference: 11/08/20. Chow et al. Acute transverse myelitis in COVID-19 infection. BMJ Case Rep.
Publication date / reference: 11/08/20. Figueiredo et al. Peripheral facial paralysis as presenting symptom of COVID-19 in a pregnant woman. BMJ Case Rep.
Publication date / reference: 11/08/20. Ray. Miller Fisher syndrome and COVID-19: is there a link? BMJ Case Rep.
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Publication date / reference: 11/08/20. Bolaji et al. Extensive cerebral venous sinus thrombosis: a potential complication in a patient with COVID-19 disease. BMJ Case Rep.
Publication date / reference: 11/08/20. Smith et al. COVID-19-associated brief psychotic disorder. BMJ Case Rep.
Publication date / reference: 11/08/20. Janocha-Litwin et al. Neurological complications of SARS-CoV-2 infection in a 66-year-old man. Pol Arch Intern Med.
Publication date / reference: 23/07/20. Mardani et al. COVID-19 infection recurrence presenting with meningoencephalitis. New Microbes New Infect.
Publication date / reference: 10/08/20. Elshereye & Erdinc. Multiple Lacunar Cerebral Infarcts as the Initial Presentation of COVID-19. Cureus.
Publication date / reference: 13/08/20. Rocha-Filho & Voss. Persistent headache and persistent anosmia associated with COVID-19. Headache.
Publication date / reference: 30/07/20. Liu et al. Stroke as a delayed manifestation of multi-organ thromboembolic disease in COVID-19 infection. J Neurol Sci.
Publication date / reference: 25/06/20. Bhatta et al. New-Onset Seizure as the Only Presentation in a Child With COVID-19. Cureus.
Publication date / reference: 17/07/20. Eshak et al. Dysautonomia: An Overlooked Neurological Manifestation in a Critically ill COVID-19 Patient. Am J Med Sci.
Publication date / reference: 01/08/20. Naddaf et al. Guillain-Barré syndrome in a patient with evidence of recent SARS-CoV-2 infection. Mayo Clin Proc.
Publication date / reference: 05/08/20. Roy et al. A case of malignant cerebral infarction associated with COVID-19 infection. Br J Neurosurg.
Publication date / reference: 05/08/20. Ferroli et al. Long lasting hypercoagulability after subclinical COVID-19. J Thromb Thrombolysis.
Publication date / reference: 31/07/20. Pissurno et al. Anosmia in the course of COVID-19: A case report. Medicine (Baltimore).
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Publication date / reference: 30/06/20. Malayala & Raza. A Case of COVID-19- Induced Vestibular Neuritis. Cureus.
Publication date / reference: 07/08/20. Dersch et al. COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment. Mult Scler.
Publication date / reference: 07/08/20. Wurm et al. Recovery from COVID-19 in a B-cell-depleted multiple sclerosis patient. Mult Scler.
Publication date / reference: 16/07/20. Castillo et al. Hemorrhagic stroke in hispanics with severe SARS-CoV2 infection. J Neurol Sci.
Publication date / reference: 21/07/20. Wada et al. Neurological Disorders Identified during Treatment of a SARS-CoV-2 Infection. Intern Med.
Publication date / reference: 26/07/20. Westhoff et al. Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient. Am J Transplant.
Publication date / reference: 23/07/20. Abenza-Abildúa et al. ENCEPHALOPATHY IN SEVERE SARS-CoV2 INFECTION: INFLAMMATORY OR INFECTIOUS? Int J Infect Dis.
Publication date / reference: 27/7/20. Abrams et al. Severe rapidly progressive Guillain-Barré syndrome in the setting of acute COVID-19 disease.J Neurovirol.
Publication date / reference: 27/07/20. Djellaoui et al. Posterior reversible encephalopathy syndrome associated with SARS-CoV-2 infection. J Neurol Neurosurg Psychiatry. A case of PRES in non-severe SARS-CoV-2 infection. In comparison to many other cases of PRES this case is notable for the lack of requirement for respiratory assistance or confounding factors such as ARDS, cytokine storm syndrome, or critical illness-related encephalopathy. The authors speculate that the absence of these factors suggests that SARS-CoV-2 endotheliopathy may contribute mechanistically to cause PRES. The patient responded quickly to treatment, clinically improving within three days and with MRI signal resolved by eight days after presenting.
Publication date / reference: 27/7/20. Savić et al. Ruptured cerebral pseudoaneurysm in an adolescent as an early onset of COVID-19 infection: case report. Acta Neurochir (Wien).
Savic et al present the first reported case of an adolescent presenting with a ruptured cerebral pseudoaneurysm as the first clinical manifestation of COVID-19 (PCR confirmed). After presenting with an intracerebral haematoma secondary to the rupture of a cerebral pseudoaneurysm in the left middle cerebral artery (M2 segment), this patient received a nasopharyngeal swab for SARS-Cov-2 despite having no symptoms of COVID-19 which tested positive. The patient later went onto develop left apical pulmonary atelectasis and acute ARDS. Savic et al. postulate that the formation and subsequent rupture of the cerebral pseudoaneurysm could be a direct consequence of COVID-19 infection, however, it is not possible to tell whether the pseudoaneurysm had already formed prior to SARS-Cov-2 infection.
Publication date / reference: 27/7/20. Cotelli et al. Effortful speech with distortion of prosody following SARS-CoV-2 infection. Neurol Sci.
Publication date / reference: 30/07/20. Farley & Zuberi. COVID-19 Precipitating Status Epilepticus in a Pediatric Patient. Am J Case Rep.
Publication date / reference: 29/7/20. Cannac et al. Critical illness-associated cerebral microbleeds in COVID-19 acute respiratory distress syndrome. Neurology.
Publication date / reference: 30/07/20. Rasmussen et al. COVID-19 and Involvement of the Corpus Callosum: Potential Effect of the Cytokine Storm? AJNR Am J Neuroradiol. Speculates that astrocytic glutamate release, stimulated by cytokine storm, may trigger restriction of water diffusion in the corpus callosum.
Publication date / reference: 3/7/20. J M van den Enden et al. Fulminant cerebral edema as a lethal manifestation of COVID-19. Radiol Case Rep.
Publication date / reference: 15/7/20. Yong et al. A Rare Case of Acute Hemorrhagic Leukoencephalitis in a COVID-19 Patient. J Neurol Sci.
Publication date / reference: 31/7/20. Fadakar et al. A First Case of Acute Cerebellitis Associated with Coronavirus Disease (COVID-19): a Case Report and Literature Review. Cerebellum.
Publication date / reference: 14/07/20. Krett et al. Hemorrhagic encephalopathy associated with COVID-19. J Neuroimmunol.
Publication date / reference: 08/20. Rudilosso et al. Thalamic perforating artery stroke on computed tomography perfusion in a patient with coronavirus disease 2019. J Stroke Cerebrovasc Dis. CT perfusion studies may be useful to identify small ischemic lesions.
Publication date / reference: 07/07/20. Al Mazrouei et al. COVID-19-associated encephalopathy: Neurological manifestation of COVID-19. Radiol Case Rep.
Publication date / reference: 04/07/20. Aoud et al. A first case of Mild Encephalitis with Reversible Splenial Lesion(MERS) as a presenting feature of SARS-CoV-2. Rev Neurol (Paris).
Publication date / reference: 08/20. Dumitrascu et al. Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban. J Stroke Cerebrovasc Dis.
Publication date / reference: 08/20. Klein et al. Cerebral venous thrombosis: A typical presentation of COVID-19 in the young. J Stroke Cerebrovasc Dis.
Publication date / reference: 15/07/20. Monti et al. Anti-NMDA receptor encephalitis presenting as new onset refractory status epilepticus in COVID-19. Seizure. Treatment included immunomodulating therapies (methylprednisolone, IVIG, plasma-exchange), antiepileptic and anesthetic drugs to control refractory status epilepticus, and empirical therapies for SAR-CoV-2 infection. The patient recovered well.
Publication date / reference: 06/06/20. AlKetbi et al. Acute myelitis as a neurological complication of Covid-19: A case report and MRI findings. Radiol Case Rep.
Publication date / reference: 17/07/20. Gemcioglu et al. Acute Ischemic Stroke in a Lupus Anticoagulant-Positive Woman With COVID-19. J Clin Rheumatol.
Publication date / reference: 22/07/2020. Shawkat et al. Multiple Thrombotic Events in a 67-Year-Old Man 2 Weeks After Testing Positive for SARS-CoV-2: A Case Report. Am J Case Rep. Extreme hypercoagulability in a 67 year-old male 14 days after a positive test. The authors raised the question as to whether outpatient coagulation screening might be beneficial.
Publication date / reference: 07/20. Palao et al. Multiple sclerosis following SARS-CoV-2 infection. Multiple Sclerosis and Related Disorders
Publication date / reference: 23/07/20. Kihira et al. Fatal cerebral infarct in a child with COVID-19. Pediatr Radiol.
Publication date/ reference: 12/05/20. Farhadian et al. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. Res Sq. (pre-print)
Publication date/reference: 03/07/20. Kariyanna et al. Apical Takotsubo Cardiomyopathy in a COVID-19 Patient Presenting with Stroke: A Case Report and Pathophysiologic Insights. Am J Med Case Rep. (COVID-19 and stroke induced apical Takotsubo Cardiomyopathy).
Publication date/reference: 25/07/20. Siepmann et al. Neuralgic amyotrophy following infection with SARS-CoV-2. Muscle Nerve.
Publication date/reference: 24/07/20. Grimaldi et al. Autoimmune encephalitis concomitant with SARS-CoV-2 infection: insight from 18 F-FDG PET imaging and neuronal autoantibodies. J Nucl Med.
Publication date / reference: 31/10/2020 Gillet & Jordan. Severe psychiatric disturbance and attempted suicide in a patient with COVID-19 and no psychiatric history. BMJ Case Reports.
Publication date / reference: 12/2020. Alpert et al. Cytokine storm induced new onset depression in patients with COVID-19. A new look into the association between depression and cytokines -two case reports. Brain Behav Immun Health.
Publication Date / Reference: 26/10/20. Tay et al. Covert Subclinical Neurocognitive Sequelae during the Rehabilitation Course of Severe Coronavirus Disease 2019: A Case Report. Am J Phys Med Rehabil.
Publication Date / Reference: 31/10/2020 Gilet et al. Severe psychiatric disturbance and attempted suicide in a patient with COVID-19 and no psychiatric history. BMJ Case Rep
Publication date / reference: 15/09/2020 Rebeiz et al. Behavioral Changes Without Respiratory Symptoms as a Presenting Sign of COVID-19 Encephalitis. Cereus.
Publication date / reference: 15/09/2020 Amouri et al. A Case of Concurrent Delirium and Catatonia in a Woman With Coronavirus Disease 2019. Psychosomatics.
Publication Date/ Reference: 26/09/2020. Mason Chacko et al. COVID-19-Induced Psychosis and Suicidal Behaviour: Case Report. SN Compr. Clin. Med.
Summary: This case report describes a 52 year-old male with no prior psychiatric history, who presented to the emergency department with acute altered mental status and mutism. His head CT and MRI were negative for acute pathology and PCR for COVID-19 was negative. He was subsequently admitted for a psychiatry consult, where he disclosed that two of his colleagues tested positive for COVID-19 causing him to feel anxious and overwhelmed. He was discharged, however returned two days later complaining of worsening paranoia, anxiety, and mutism; and his family revealed that he had attempted suicide after waking up one morning. He was admitted to the inpatient psychiatric ward where he remained anxious, and attempted suicide again. He underwent a total of 6 electroconvulsive therapy treatments, which led to clinical improvement and no further thoughts of suicide. Three weeks after discharge, he tested positive for COVID-19 antibodies indicating prior infection. This case report aims to establish coronavirus as a risk factor for severe psychosis and suicidal behaviour.
Publication date / reference: 14/07/2020. Perez et al. Postpartum consciousness disturbance: can covid-19 cause posterior reversible encephalopathy syndrome?. Rev Esp Anestesiol Reanim.
Publication date / reference: 16/09/20. Telles-Garcia et al. Suicide Attempt as the Presenting Symptom in a Patient with COVID-19: A Case Report from the United States. Case Rep Psychiatry.
Publication date / reference: 14/09/20. Haddadi et al. COVID-19: Risk of alcohol abuse and psychiatric disorders. Respir Med Case Rep.
Publication date / reference: 04/09/20. Theophanous et al. Bell’s palsy in a pediatric patient with hyper IgM syndrome and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Brain Dev.
Publication date / reference: 04/09/20. Wang et al. Coronavirus disease 2019 associated with aggressive neurological and mental abnormalities confirmed based on cerebrospinal fluid antibodies: A case report. Medicine (Baltimore).
Publication date / reference: August 2020. Losee et al. COVID-19 Delirium with Psychosis: A Case Report S D Med.
Publication date / reference: 08/08/20. Noone et al. Letter to the editor: new onset psychosis and mania following COVID-19 infection. J Psychiatr Res.
Publication date / reference: August 2020 Losee et al. COVID-19 Delirium with Psychosis: A Case Report S D Med.
Publication date / reference: 06/08/20. Payne et al. Mild COVID-19 Disease Course With Protracted Delirium in a Cognitively Impaired Patient Over the Age of 85 Years. Prim Care Companion CNS Disord.
Publication date / reference: 10/08/20. Gouse et al. Catatonia in a Hospitalized Patient with COVID-19 and Proposed Immune-Mediated Mechanism. Brain Behav Immun.
Publication date / reference: 04/08/20. Mulder et al. Autoimmune Encephalitis Presenting with Acute Excited Catatonia in a 40-Year-Old Male Patient with Covid-19. MedRxiv (preprint).
Publication date / reference: 06/08/20. Payne et al. Mild COVID-19 Disease Course With Protracted Delirium in a Cognitively Impaired Patient Over the Age of 85 Years. Prim Care Companion CNS Disord.
Publication date / reference: 17/07/20 Shinjo et al. Transcranial direct current stimulation relieves the severe anxiety of a patient with COVID-19. Brain Stimul.
Publication date / reference: 22/07/20. Persistent Psychotic Symptoms following Covid-19 Disease. BJPsych Open.
Publication date / reference: 23/07/2020. Llesuy & Sidelnik Death From COVID-19 in a Patient Receiving Clozapine:Factors Involved and Prevention Strategies to Consider. Prim Care Companion CNS Disord.
Publication date / reference: 14/07/20. Soysal & Kara. Delirium as the first clinical presentation of the coronavirus disease 2019 in an older adult. Psychogeriatrics.
Publication date / reference: 06/07/20. Mehra et al. Why involvement of mental health professionals and screening for past mental illness is important in persons with COVID-19 infection: A case report. Asian J Psychiatr
Publication date / reference: 15/07/20. Young et al. Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration? Brain Behav Immun.
Publication date / reference: 16/07/20. Utukuri et al. Possible Acute Disseminated Encephalomyelitis Related to Severe Acute Respiratory Syndrome Coronavirus 2 Infection. AJNR Am J Neuroadiol.
Publication date / reference: 13/07/20. Kushlaf. COVID ‐19 in MuSK Myasthenia Gravis: A Case Report. Muscle Nerve.
Publication date / reference: 01/07/20. Mantero et al. Recurrent Transient Ischemic Attack in a Young Patient with COVID-19. J Clin Neurol.
Publication date / reference: Cani et al. Frontal encephalopathy related to hyperinflammation in COVID-19. J Neurol.
Publication date / reference: 12/07/20. Frank et al. Guillain-Barré Syndrome Associated with SARS-CoV-2 Infection in a Pediatric Patient. J Trop Pediatr. – reported as the first paediatric case of GBS + COVID-19.
Publication date / reference: 11/07/20. Roy-Gash et al. COVID-19-associated acute cerebral venous thrombosis: clinical, CT, MRI and EEG features. Crit Care.
Publication date / reference: 15/07/20. Homma et al. Coronavirus Disease-19 Pneumonia with Facial Nerve Palsy and Olfactory Disturbance. Intern Med.
Publication date / reference: 15/07/20. Soldatelli et al. Neurovascular and perfusion imaging findings in coronavirus disease 2019: Case report and literature review. Neuroradiol J.
Publication date / reference: 20/06/20. Allard et al. Acute hypothermia in Covid 19: A case report. eNeurologicalSci.
Publication date / reference: 05/06/20. Enner et al. Central Apnea in an Adolescent With COVID-19. Pediatr Neurol.
Publication date / reference: 08/07/20. Majadas et al. A Case With Psychotic Disorder as a Clinical Presentation of COVID-19. Psychiatry Clin Neurosci.
Publication date / reference: 09/07/20. de Oca Rivas et al. Reactive Psychosis in a Health Care Worker During the COVID-19 Pandemic. Prim Care Companion CNS Disord.
Publication date / reference: 10/07/20. Delamarre et al. COVID-19-associated Acute Necrotising Encephalopathy Successfully Treated With Steroids and Polyvalent Immunoglobulin With Unusual IgG Targeting the Cerebral Fibre Network. J Neurol Neurosurg Psychiatry.
Publication date / reference: 16/06/20. Mahboob et al. Large Vessel Stroke and COVID-19: Case Report and Literature Review. eNeurologicalSci.
Publication date / reference: 07/07/20. Otluoglu et al. Encephalomyelitis Associated With Covid-19 Infection: Case Report. Br J Neurosurg.
Publication date / reference: 25/06/20. Singh & Givindarajan. COVID-19 and Generalized Myasthenia Gravis Exacerbation: A Case Report. Clin Neurol Neurosurg.
Publication date / reference: 07/07/20. Khoo et al. Postinfectious Brainstem Encephalitis Associated With SARS-CoV-2. J Neurol Neurosurg Psychiatry. Corticosteroid responsive.
Publication date / reference: 07/07/20. Slootjes et al. Acute stroke care during the COVID-19 pandemic: difficult, but not impossible! Acta Neurol Belg.
Publication date / reference: 08/07/20 Jaunmuktane et al. Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19. Acta Neuropathol.
Publication date / reference: 24/06/20. Regev et al. Pediatric inflammatory multisystem syndrome with central nervous system involvement and hypocomplementemia following SARS-CoV-2 infection. Pediatr Infect Dis J.
Publication date / reference: 08/07/20. Moreira et al. Bilateral Paresthesia Associated With Cardiovascular Disease and COVID-19. Oral Dis.
Publication date / reference: 08/07/20. Tiet & AlSheik. Guillain-Barré Syndrome Associated With COVID-19 Infection: A Case From the UK. BMJ Case Rep.
Publication date / reference: 08/07/20. Mendez-Guerrero et al. Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection. Neurology.
Publication date / reference: 08/07/20. Cebrian et al. Headache and Impaired Consciousness Level Associated With SARS-CoV-2 in CSF: A Case Report. Neurology.
Publication date / reference: 08/07/20. Chen et al. Hidden Risk of Nosocomial Transmission: A Presymptomatic Novel Coronavirus disease-19 (COVID-19) Case With Ischemic Stroke. J Thoracic Dis.
Publication date / reference: 09/07/20. Agosti et al. Is Guillain-Barrè Syndrome Triggered by SARS-CoV-2? Case Report and Literature Review. Neurol Sci.
Publication date / reference: 11/07/20. Khalifa et al. Guillain-Barre Syndrome Associated With SARS-CoV-2 Detection and a COVID-19 Infection in a Child. J Pediatric Infect Dis Soc.
Publication date / reference: 19/05/20. Sher et al. COVID-19-associated hyperactive Intensive Care Unit delirium with proposed pathophysiology and treatment: a case report. Psychosomatics.
Publication date / reference: 27/05/20. Caan et al. A case of catatonia in a man with COVID-19. Psychosomatics. Lorazepam responsive.
Publication date / reference: 06/20. De Stefano et al. Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient. Clin Neurophysiol Pract.
Publication date / reference: 06/20. de Oliveira et al. Bilateral trochlear nerve palsy due to cerebral vasculitis related to COVID-19 infection. Arq Neuropsiquiatr.
Publication date / reference: 01/07/20. Lima et al. Acute ischemic stroke in a patient with COVID-19. Arq Neuropsiquiatr.
Publication date / reference: 27/06/20. Coline et al. COVID-19 as triggering co-factor for cortical cerebral venous thrombosis? J Neuroradiol.
Publication date / reference: 29/06/20. Pun et al. H3K27M-mutant diffuse midline glioma with extensive intratumoral microthrombi in a young adult with COVID-19-associated coagulopathy. Acta Neuropathol.
Publication date / reference: 30/06/20. Zachariadis et al. Transverse myelitis related to COVID-19 infection. J Neurol.
Publication date / reference: 24/06/20. Falcone et al. Acute abducens nerve palsy in a patient with the novel coronavirus disease (COVID-19). J AAPOS.
Publication date / reference: 29/06/20. Zhai et al. The impact of COVID-19 on ischemic stroke. Diagn Pathol.
Publication date / reference: 29/06/20. Isenmann et al. COVID-19: Variable symptoms in mild course: olfactory loss and increased resting heart rate. Dtsch Med Wochenschr.
Publication date / reference: 24/06/20. Zoghi et al. A case of possible atypical demyelinating event of the central nervous system following COVID-19. Mult Scler Relat Disord.
Publication date / reference: 12/06/20 Tankisi et al. Critical illness myopathy as a consequence of COVID-19 infection. Clin Neurophysiol.
Publication date / reference: 01/07/20. Fischer et al. Intact brain network function in an unresponsive patient with COVID-19. Ann Neurol. Interesting case of a patient with prolonged unresponsiveness, structural brain abnormalities, yet intact functional network connectivity (later recovered some cognitive ability).
Publication date / reference: 26/06/20. Zhou et al. Myelin Oligodendrocyte Glycoprotein antibody associated optic neuritis and myelitis in COVID-19. J Neuroopthalmol.
Publication date / reference: 26/06/20 Le Guennec et al. Orbitofrontal involvement in a neuroCOVID-19 patient. Epilepsia.
Publication date / reference: 25/06/20 Bracaglia et al. Acute Inflammatory Demyelinating Polyneuritis in Association With an Asymptomatic Infection by SARS-CoV-2. J Neurol.
Publication date / reference: 25/06/20 Virhammar et al. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology.
Publication date / reference: 25/06/20 Kulick-Soper et al. Pearls & Oy-sters: Bilateral globus pallidus lesions in a patient with COVID-19. Neurology.
Publication date / reference: 25/06/20 Hutchins et al. COVID-19-Associated Bifacial Weakness with Paresthesia Subtype of Guillain-Barré Syndrome. AJNR Am J Neuroradiol.
Publication date / reference: 24/06/20 McAbee et al. Encephalitis Associated with COVID-19 Infection in an 11-Year-Old Child. Pediatr Neurol.
Publication date / reference: 24/06/20 Cariddi et al. Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. J Neurol
Publication date / reference: 20/06/20 Li et al. Anosmia and olfactory tract neuropathy in a case of COVID-19. J Microbiol Immunol Infect
Publication date / reference: 20/06/20 Amin Farzi et al. Guillain-Barré syndrome in a patient infected with SARS-CoV-2, a case report. J Neuroimmunol.
Publication date / reference: 20/06/20 Domingues et al. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol.
Publication date / reference: 18/06/20 Acharya et al. Unique case of central retinal artery occlusion secondary to COVID-19 disease. IDCases.
Publication date / reference: 18/06/20 Abdi et al. The Association of SARS-CoV-2 Infection and Acute Disseminated Encephalomyelitis Without Prominent Clinical Pulmonary Symptoms. J Neurol Sci.
Publication date / reference: 08/06/20. Lyons et al. Seizure with CSF lymphocytosis as a presenting feature of COVID-19 in an otherwise healthy young man. Seizure.
Publication date / reference: 08/06/20 Guijarro-Castro et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection. Comments after 16 published cases. Neurología (although the title doesn’t suggest it, this paper presents the case of a 70 year old man with GBS and SARS-CoV-2 infection).
Publication date / reference: 06/06/20 Jang et al. COVID-19 leading to acute encephalopathy in a patient with heart transplant. J Heart Lung Transplant.
Publication date / reference: 16/6/20 Dugue et al. Neurologic Manifestations in an Infant With COVID-19. Neurology.
Publication date / reference: 15/6/20 Kaya et al. Transient Cortical Blindness in COVID-19 Pneumonia; A PRES-like Syndrome: Case Report. J Neurol Sci.
Publication date / reference: 15/06/2020 Aranda-Abreu et al. Use of amantadine in a patient with SARS-Cov-2. J Med Virol.
Publication date / reference: 14/6/20 Webb et al. Guillain-Barré Syndrome Following COVID-19: A Newly Emerging Post-Infectious Complication. BMJ Case Rep.
Publication date / reference: 14/06/20Zhang et al. COVID-19 Associated Myositis with Severe Proximal and Bulbar Weakness. Muscle Nerve.
Publication date / reference: 14/06/20Webb et al. COVID-19: A Newly Emerging Post-Infectious Complication. BMJ Case Rep.
Publication date / reference: 14/06/20Mawhinney et al. Neurotropism of SARS-CoV-2: COVID-19 Presenting with an Acute Manic Episode. BMJ Case Rep.
Publication date / reference: 13/06/20Kilinc et al. Guillain-Barré Syndrome After SARS-CoV-2 Infection. Eur J Neurol.
Publication date / reference: 12/06/20 Helbok et al. Guillain-Barré syndrome in a patient with antibodies against SARS-COV-2. Eur J Neurol.
Publication date / reference: 12/6/20Faucher et al. Isolated post SARS-CoV-2 diplopia. J Neurol.
Publication date / reference: 09/06/20Kadono et al. A Case of COVID-19 Infection Presenting with a Seizure Following Severe Brain Edema. Seizure.
Publication date / reference: 09/06/20Guillan et al. Unusual Simultaneous Cerebral Infarcts in Multiple Arterial Territories in a COVID-19 Patient. Thromb Res.https://pubmed.ncbi.nlm.nih.gov/32531083/
Publication date / reference: 19/05/20 Gill et al. COVID-19-associated pulmonary and cerebral thromboembolic disease. Radiol Case Rep.
2. REVIEWS, EDITORIALS AND POSITION PAPERS
Publication date / reference: 10/11/20 Chen et al. Clinical characteristics of inpatients with Coronavirus disease 2019 and acute ischemic stroke: from epidemiology to outcomes. Curr Neurovasc Res.
Summary: The authors of this review report that the incidence of acute ischaemic stroke amongst patients with COVID-19 was seen to vary from 0.9% to 4.6% in the literature and that the National Institute of Health Stroke Scale score of COVID-19 patients with acute ischaemic stroke was higher than historical acute ischaemic stroke patients, with a proportion of large vessel occlusion of 64.2%. COVID-19 patients with acute ischaemic stroke were seen to have high levels of D-dimer, fibrinogen, CRP and ESR and their pooled mortality was 38%. Compared with COVID-19 negative acute ischaemic stroke patients in the same period in 2020 and 2019, COVID-19 patients with acute ischaemic stroke were reported to have had a worse prognosis.
Publication date / reference: 09/09/2020. Mudatsir Mudatsir et al. Predictors of COVID-19 severity: a systematic review and meta-analysis. F1000Res.
Summary: This systematic review and meta-analysis was conducted to identify the predictors associated with poor clinical outcomes in patients with COVID-19. In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included in the analysis. The authors identified numerous comorbidities, which varied based on the severity of COVID-19. They concluded that over 30 risk factors are associated with an increased risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.
Publication date / reference: 3/11/2020. Choi & Lee. Neuroimaging findings of brain MRI and CT in patients with COVID-19: A systematic review and meta-analysis. Eur J Radiol.
Summary: This systematic review and meta-analysis was conducted to evaluate the incidences of abnormal neuroimaging findings in patients with COVID-19. The authors searched for original articles reporting imaging findings of the brain in adult patients with COVID-19 between January 1, 2020 and October 9, 2020. They identified 21 eligible papers, including 2125 patients. The pooled incidences of cerebral microhemorrhages, acute spontaneous ICH, acute/subacute infarcts, and encephalitis/encephalopathy were 6.9%, 5.4%, 24.0%, and 3.3%, respectively. In the subgroup meta-regression analysis, patients with mean or median ages over 65 years showed a lower incidence of encephalitis/encephalopathy, and patients in ICU had higher incidences of cerebral microhemorrhages and encephalitis/encephalopathy. They concluded that considerable incidences of abnormal neuroimaging findings have been reported in patients with COVID-19. Acute to subacute cerebral infarction was the most prevalent neuroimaging finding.
Publication date / reference: 5/11/20. Al-Zahrani et al. SARS-CoV-2 associated COVID-19 in Geriatric Population: A Brief Narrative Review. Saudi J Biol Sci.
Publication date / reference: 11/11/20. Mehta et al. COVID‐19, thromboembolic risk, and Virchow’s triad: Lesson from the past. Clin Cardiol.
Publication date / reference: 10/11/20. Li et al. Role of angiotensin-converting enzyme 2 in neurodegenerative diseases during the COVID-19 pandemic. Aging (Albany NY).
Publication date / reference: 26/08/20. Alonso-Lana et al. Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia. Front Aging Neurosci.
Publication date / reference: 03/11/2020. Bellocchio et al., Environmental Issues and Neurological Manifestations Associated with COVID-19 Pandemic: New Aspects of the Disease? Int J Environ Res Public Health
Summary: This is a review of the literature regarding COVID-19 and its manifestations in the neurological system. They talk about the mechanism of CNS invasion and damage via hypoxic brain injury and immune mediated injury. Their key findings suggest that there is evidence of links to encephalopathy, CVA, acute myelitis, encephalitis as well as peripheral nervous system symptoms and links with GBS. Overall, they found that anosmia and ageusia were prominent and maintain that neurological symptoms are a key clinical feature of COVID-19.
Publication date / reference: 7/11/20. Mui et al. Thromboembolic complications of COVID-19. Emerg Radiol.
Publication date / reference: 02/11/20. Zimmer et al. Prenatal exposure to viral infection and neuropsychiatric disorders in offspring: a review of the literature and recommendations for the COVID-19 pandemic. Brain Behav Immun.
Publication date / reference: 1/11/20 Moreira et al. The psychiatric and neuropsychiatric repercussions associated with severe infections of COVID-19 and other coronaviruses. Prog Neuropsychopharmacol Biol Psychiatry.
Publication date / reference: 31/10/20 Kamel et al. Hyperthrombotic milieu in COVID-19 patients. Cells.
Publication date / reference: 28/10/20. Medicherla et al. Cerebral Venous Sinus Thrombosis in the Coronavirus Disease 2019 Pandemic. J Neuroophthamol.
Publication date / reference: 15/10/20. Brandenburg et al. Why individuals with cerebral palsy are at higher risk for respiratory complications from COVID-19. J Pediatr Rehabil Med.
Publication date / reference: 7/06/20. MadaniNeishaboori et al. Central Nervous System Complications in COVID-19 Patients; a Systematic Review and Meta-Analysis based on Current Evidence. Arch Acad Emerg Med.
Summary: the authors conducted a systematic review and meta-analysis to determine the prevalence of neurological complications in patients with confirmed COVID-19. Due to the early point in the pandemic that this study was conducted, only seven suitable studies were found. Similarly to other epidemiological studies, encephalopathy and cerebrovascular accidents were the most common manifestations. Leptomeningeal enhancement, dysexecutive syndrome, brain perfusion abnormalities and ataxia were also reported. Based on their meta-analysis, the overall prevalence of neurological abnormalities was 6.27%. However, there was significant heterogeneity with the included studies (I2 = 90%).
Publication Date / Reference: 30/10/2020 Cagnazzo et al. Neurological manifestations of patients infected with the SARS-CoV-2: a systematic review of the literature. J Neurol.
Summary: This systematic review of the literature up to October 2020 found 39 eligible studies. Of a total 68,361 laboratory-confirmed COVID-19 patients, 21.3% presented with neurological symptoms; Headache (5.4%), skeletal muscle injury (5.1%), psychiatric disorders (4.6%), impaired consciousness (2.8%), gustatory/olfactory dysfunction (2.3%), acute cerebrovascular events (1.4%), and dizziness (1.3%), were the most frequently reported neurological manifestations. Ischemic stroke occurred among 1.3% of COVID-19 patients. Data on neurological manifestations are missing in some of the included studies because they were not designed to investigate neurological symptoms.Therefore higher frequency of most benign neurological manifestations as headache or anosmia in patients with a more favorable condition and so not hospitalized cannot be excluded.
Publication Date / Reference: 26/10/2020 Nannoni et al. EXPRESS: Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke.
Summary: This systematic review evaluated published articles on acute CVD in COVID-19 between December 2019- September 2020. Of these 61 articles were included in the meta-analysis which found the prevalence of acute CVD in COVID-19 to be 1.4%. Of these, the majority were acute ischaemic stroke (87.4%). Having an acute CVD in COVID-19 was associated with increased age, hypertension, diabetes, coronary heart disease and severe infection. Those with COVID-19 associated stroke were also more likely to be younger, have a greater NIHSS, greater in-hospital mortality and increased frequency of large vessel occlusion. The authors caution that assumptions on the stroke incidence amongst people with COVID-19 were mostly based on small, single-centre observational studies, and therefore should be regarded with caution.
Publication Date/Reference: 08/2020. Marchese-Ragona et al. Loss of smell in COVID-19 patients: a critical review with emphasis on the use of olfactory tests. Acta Otorhinolaryngol Ital.
Publication Date/Reference: 30/10/20. Divani et al. Central Nervous System Manifestations Associated with COVID-19. Curr Neurol Neurosci Rep.
Publication Date/Reference: 30/10/2020 Bolay et al. Are Migraine Patients at Increased Risk for Symptomatic Coronavirus Disease 2019 Due to Shared Comorbidities? Headache.
Publication Date/Reference: 30/09/20. Mondal et al. Spectrum of spinal cord involvement in COVID-19: a systematic review. MedRxiv Preprint.
Summary: This pre-print systematic review analysed 21 case reports of patients with suspected or confirmed COVID-19 and suspected or confirmed spinal cord demyelinating disorders. Elevated CSF protein was seen in 13 cases, whilst long extensive transverse myelitis was seen in nine patients. Notably, SARS-CoV-2 testing was only positive in 5 cases, negative in 13 cases, not performed in two cases and not reported in one case.
Publication Date/Reference: 25/09/2020. Wijeratne et al. Acute ischemic stroke in COVID-19: a case-based systematic review. Front Neurol.
Summary: The authors of this systematic review identified 18 articles (n=87) including nine case reports, six case series, two prospective cohort studies and one retrospective cohort study. It was observed that hypercoagulative markers such as D-dimer were elevated in all patients early in the disease process, and a positive correlation emerged when comparing neutrophil-lymphocyte ratio (NLR) at time of admission and duration before onset of features of acute ischaemic stroke. In addition, raised NLR, CRP, ferritin, D-dimer and fibrinogen levels were seen to be associated with poor prognosis of acute ischaemic stroke.
Publication Date/Reference: 27/10/2020 Jahrami et al. Sleep problems during COVID-19 pandemic by population, a systematic review and meta-analysis. J Clin Sleep Med.
Summary: In this systematic review and meta-analysis Jahrami and colleagues pooled results from 44 papers (N=54,231) to investigate the prevalence of sleep problems (measured by Pittsburgh Sleep quality index, PSQ1 score). during COVID-19. They found that the global pooled prevalence rate of sleep problems among general populations were 32.3%, health care workers had comparable rates of 36%. However, COVID-19 patients appeared to be most affected with a pooled rate of 74.8%. The authors highlighted that the findings are limited by high heterogeneity of the data. In addition, other co-founders that impact sleep (e.g social factors, lifestyle factors, stress related disorders) were not included in many of the studies.
Publication Date/Reference: 06/10/2020. Lee et al. Stroke and novel coronavirus infections in humans: A systematic review and meta-analysis. Front Neurol.
Summary: In this comprehensive systematic review and meta-analysis, authors analysed studies related to stroke and COVID-19 from inception up to June 4th 2020. A total of twenty eight studies were included in the final analysis. The authors report a 1.1% pooled frequency of stroke in COVID-19 patients. Despite the low frequency, COVID-19 patients who suffered strokes had a more severe infection and poorer prognosis, with a higher mortality rate (46.7%).
Publication date/reference: 28/10/2020. Yunsung Kim et al. A Comprehensive Review of Neurologic Manifestations of COVID-19 and Management of Pre-existing Neurologic Disorders in Children. J Child Neurol.
Summary: In this review, the potential neurotropism of SARS-CoV-2, known neurologic manifestations of COVID-19 in children, and management of preexisting pediatric neurologic conditions during the COVID-19 pandemic are discussed.
Publication date/reference: 19/10/2020. Arun Raj Antony et al. Systematic review of EEG findings in 617 patients diagnosed with COVID-19. Seizure.
Summary: This systematic review synthesizes the data on EEG findings in COVID-19. Frontal EEG patterns are reported to be a characteristic finding in COVID-19 encephalopathy, and have been suggested as a biomarker for COVID-19 encephalopathy. EEG abnormalities are common in COVID-19, and the authors describe the correlation between this and disease severity.
Publication date/reference: 27/10/2020. Aneesha Achar et al. COVID-19-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Relevance. Cells.
Summary: This review highlights the possible routes by which SARS-CoV-2 may invade the central nervous system (CNS). The authors provide insight into recent case reports of COVID-19-associated neurological disorders, namely ischaemic stroke, encephalitis, encephalopathy, epilepsy, neurodegenerative diseases, and inflammatory-mediated neurological disorders.
Publication date / reference: Nov, 2020 Wang et al., Care for Patients with Stroke During the COVID-19 Pandemic: Physical Therapy and Rehabilitation Suggestions for Preventing Secondary Stroke. J Stroke Cerebrovasc Dis
This review aims to evaluate the neurological manifestations in COVID-19 patients; in particular, the suggestion of neurological complications in COVID-19 patients with stroke. The authors give an overview of pathophysiology, therapeutics and neurorehabilitation techniques. For the latter, TENS, virtual reality and home exercise programmes have been suggested. The authors also talk about the pathophysiology: the importance of the ACE2 receptor in viral transmission and the importance of possible interactions with anti-COVID medications.
Publication date / reference: 22/09/2020. Rohit Bhatia et al. Stroke in Coronavirus Disease 2019: A Systematic Review. J Stroke.
Summary: This systematic review aims to report the characteristics of stroke in patients with COVID-19. The authors identified 30 relevant articles involving 115 patients with acute or subacute stroke with COVID-19, and found that stroke was ischemic in the majority of patients. Major vascular risk factors included hypertension,dyslipidemia and diabetes. The authors concluded that the association between stroke and COVID-19 is multifactorial, and involves vascular risk factors, proinflammatory and prothrombotic state. Future studies using prospectively collected data will help confirm this hypothesis.
Publication date / reference: 20/10/2020 Naeimi et al. Update on cerebrovascular manifestations of COVID-19. Neurol Sci.
Publication date / reference: 16/10/2020 Alshebri et al. Neurological Complications of SARS-CoV, MERS-CoV, and COVID-19. SN Compr Clin Med.
Publication date / reference: 16/10/20. Gasmi et al. Neurological involvement of SARS-CoV2 infection. Mol Neurobiol.
Publication date / reference: 09/20. McClafferty et al. Approach to critical illness myopathy and polyneuropathy in the older SARS-CoV-2 patients. J Clin Neurosci.
Publication date / reference: 22/10/20. Pergolizzi Jr et al. Potential Neurological Manifestations of COVID-19: A Narrative Review. Postgrad Med.
Publication date / reference: 21/10/20. Ibrahim et al. Neurological Manifestations in Coronavirus Disease 2019 (COVID-19) Patients: A Systematic Review of Literature. CNS Spectr.
Publication date / reference: 14/10/20. Rosen et al. Extrapulmonary Manifestations of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection. J Med Virol.
Publication date / reference: 19/10/20. Hu et al. Neurotropism of SARS-CoV-2 and its neuropathological alterations: similarities with other coronaviruses. Neurosci Biobehav Rev.
Publication date / reference: 06/10/2020 Valiuddin et al. Update on Neurological Manifestations of SARS-CoV-2. West J Emerg Med
Publication date/ reference: 30/09/20. Ma et al. From the perspective of Traditional Chinese Medicine: Treatment of mental disorders in COVID-19 survivors. Biomed Pharmacother
Publication date / reference: 22/10/20. Hussain et al. Guillian Barré syndrome and COVID-19: Possible role of the cytokine storm. Autoimmun Rev.
Publication date / reference: 09/20. Haddadi & Asadian. Coronavirus Disease 2019: Latest Data on Neuroinvasive Potential. Iran J Med Sci.
Publication date / reference: 28/05/20. Ritchie et al. The cognitive consequences of the COVID-19 epidemic: collateral damage?. Brain Commun.
Publication date / reference: 21/10/20. Assari. COVID-19 Pandemic and Neurological Disease: A Critical Review of the Existing Literature. Hosp Pract Res.
Publication date / reference: 12/20. Narula et al. Seizure and COVID-19: Association and review of potential mechanism. Neurol Psychiatry Brain Res.
Publication date / reference: 21/10/20 Favas et al. Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions. Neurol Sci.
Summary: This systematic review and meta-analysis aims to estimate the prevalence of neurological manifestations of SARS-CoV-2 infection. The authors identified 212 studies for the systematic review and 74 studies for the meta-analysis. They found that pooled prevalence of each neurological manifestations are, taste disturbances (38.5%), smell disturbances (35.8%), myalgia (19.3%), headache (14.7%), altered mental status (9.6%), dizziness (6.1%), and stroke (2.3%). The authors concluded that neurological symptoms are common in SARS-CoV-2 infection therefore identifying some neurological manifestations can be used to screen patients with COVID-19.
Publication date / reference: 19/10/20 Chua et al. Neurological manifestations in COVID-19: a systematic review and meta-analysis. Brain Inj.
Summary: This systematic review and meta-analysis aims to determine the clinical characteristics of neurological manifestations in COVID-19. The authors included 48 relevant studies involving 70 patients with 73 neurological manifestations, which were olfactory and gustatory dysfunction (59.9% and 57.5%), stroke (53.4%), Guillain-Barré syndrome and variants (24.7%), meningitis, encephalitis, encephalopathy, or myelitis (15.1%), and seizures (6.8%). Neurological disease occurred 8.1 ± 6.8 days from initial symptoms. Average mortality rate was 17.8%. The authors concluded that there is significant morbidity and mortality associated with COVID-19 neurological manifestations.
Publication date / reference: 11/20 Xu et al. The Association of Cerebrovascular Disease with Adverse Outcomes in COVID-19 Patients: A Meta-Analysis Based on Adjusted Effect Estimates. J Stroke Cerebrovasc Dis.
Summary: This meta-analysis aims to address the association between cerebrovascular disease and adverse outcomes in COVID-19 patients by using a quantitative meta-analysis based on adjusted effect estimates. The authors included 12 relevant studies with 10,304 patients and found a significant association between cerebrovascular disease and adverse outcomes (pooled effect = 2.05). Patients with history of cerebrovascular disease had more likelihood to progress fatal outcomes (pooled effect = 1.78). The authors concluded that cerebrovascular disease was an independent risk factor for predicting the adverse outcomes, particularly fatal outcomes, in COVID-19 patients on the basis of adjusted effect estimates.
Publication date / reference: 14/10/2020. Kumar et al. Neurological manifestations and comorbidity associated with COVID-19: an overview. Neurol Sci.
Publication date / reference: 12/10/20. Mansoor et al. Impact of disease-modifying drugs on severity of COVID-19 infection in multiple sclerosis patients. J Med Virol.
Publication date / reference: 8/10/20. Scutelnic & Heldner. Vascular Events, Vascular Disease and Vascular Risk Factors-Strongly Intertwined with COVID-19. Curr Treat Options Neurol.
Publication date / reference: 23/09/2020 AlSamman et al. Non-respiratory presentations of COVID-19, a clinical review. Am J Emerg Med.
Publication date/ reference: 17/09/20. Katyal et al. Neuromuscular Complications With SARS-COV-2 Infection: A Review. Front Neurol.
Publication date / reference: 17/09/2020. Chaná-Cuevas et al. The Potential Role of SARS-COV-2 in the Pathogenesis of Parkinson’s Disease. Front Neurol.
Publication date / reference: 16/09/20. Eshraghi et al. Potential Mechanisms for COVID-19 Induced Anosmia and Dysgeusia. Front Physiol.
Publication date / reference: 11/20. Tisdale and Chwalisz. Neuro-ophthalmic manifestations of coronavirus disease 19. Curr Opin Ophthalmol.
Summary: In this literature review the authors shed light on reports of novel neuro-ophthalmic disease in COVID-19, including acute onset visual loss, optic neuritis, cranial neuropathies and Miller Fisher syndrome, going on to make recommendations for clinical practice.
Publication date / reference: 05/10/20 Puccioni-Sohler et al. Current evidence of neurological features, diagnosis, and neuropathogenesis associated with COVID-19 Rev Soc Bras Med Trop.
Publication date / reference: 02/10/20. Deng et al. The prevalence of depression, anxiety, and sleep disturbances in COVID-19 patients: a meta-analysis. Ann N Y Acad Sci.
Summary: The authors of this meta-analysis reviewed 31 studies (n = 5153) with COVID-19 patient populations and found that the pooled prevalence of depression was 45%, anxiety 47% and sleeping disturbances 34%. No significant differences in prevalence were noted between genders though depression and anxiety prevalence estimates varied according to screening tool used.
Publication date / reference: 02/10/20. Verma et al. Brain and COVID-19 crosstalk: pathophysiological and psychological manifestations. ACS Chem NeuroSci.
Summary: The authors of this narrative review discuss both neurological pathologies that have been linked with COVID-19, as well as the psychological impact of COVID-19 and the outbreak itself.
Publication date/reference: 01/10/20 Liu et al. Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement in the lethality of SARS-CoV-2 infection J Med Virol.
Publication date / reference: 26/09/2020 Zangbar et al. A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View. Mol Neurobiol.
Summary: Narrative review of the most common neurological manifestations and complications of SARS-CoV-2 and their possible relation to the expression and function of ACE2.
Publication date / reference: 28/09/20. Sanghi et al. Ocular Complications in the Prone Position in the Critical Care Setting: The COVID-19 Pandemic. J Intensive Care Med.
Summary: “Sight-threatening ophthalmic disorders potentiated by proning include ocular surface disease, acute angle closure, ischemic optic neuropathy, orbital compartment syndrome and vascular occlusions.” This is a systematic review “of all ocular complications associated with prone positioning in ICU, with a focus on challenges posed by COVID-19.” The authors conclude that “COVID-19 patients may be more susceptible to ocular complications with increased proning practices and increasing demand on critical care staff.”
Publication date / reference: 10/7/20 Somani & Agnihotri. Emerging Neurology of COVID-19
Summary: A narrative review of common neurological manifestations of COVID-19, in particular concern of higher incidence in individuals with chronic neurological conditions. Review the literature along with anecdotal evidence and consider potential pathophysiological mechanisms.
Publication date / reference: 18/9/202 Valencio-Enciso et al. Time of Stroke Onset in Coronavirus Disease 2019 Patients Around the Globe: A Systematic Review and Analysis
Summary: A systematic review looking at the severity of COVID-19 and the timing of stroke. They analysed 47 studies which included 176 patients. They found that mean onset time for stroke was 9 days from symptom onset with shorter time periods noted for mild-moderate disease. Inflammatory and hypercoagulability markers were elevated in this cohort and hypothesise hypercoagulability secondary to SARS-CoV-2 is an underlying cause for stroke in these patients.
Publication date / reference: 28/09/20. Svegedi et al. Stroke as a Potential Complication of COVID-19-Associated Coagulopathy: A Narrative and Systematic Review of the Literature. J Clin Med.
Summary: Narrative and systematic review of stroke associated with COVID-19 coagulopathy. The authors concluded that ischemic stroke was more common in COVID-19 than haemorrhagic and that stroke held unfavourable outcomes.
Publication date / reference: 30/09/20. Jarrahi et al. Neurological consequences of COVID-19: what have we learned and where do we go from here?. J Neuroinflammation.
Publication Date/Reference: 29/09/2020. The Neurological Complexities and Prognosis of COVID-19. Inderbir Padda et al. SN Compr Clin Med.
Summary: A systematic review looking at the mechanisms, neurological manifestations, and complications of SARS-CoV-2 on the CNS and PNS. This review includes case reports, case series, meta-analyses, cohort studies, retrospective studies, and narrative reviews in order to investigate COVID-19 associated CNS and PNS complications. The authors concluded that the most common CNS manifestations in COVID-19 patients included headache and dizziness, while the most common PNS symptoms were changes in smell and taste.
Publication date / reference: 29/08/20. Yamakawa et al. Clinical Characteristics of Stroke with COVID-19: A Systematic Review and Meta-Analysis. J Stroke Cerebrovasc Dis.
Summary: The authors conducted a systematic review and meta-analysis to probe the complex relationship between stroke and COVID-19 (search done on 10/05/20). From their meta-analysis, the frequency of stroke in hospitalised COVID-19 patients was 1.1%, based on retrospective cohort studies with moderate heterogeneity (62.9%). Despite including case series with younger patients without comorbidities, the average age of patients with stroke was 66.6. Of interest, altered mental status was a common presenting complaint in patients with stroke.
Publication date / reference: 30/09/20. Williams et al. Insult to injury- potential contribution of COVID-19 to neuroinflammation and the development of HIV-associated neurocognitive disorders. AIDS Res Hum Retroviruses.
Publication date / reference: 25/09/20. Lima et al. Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System. Curr Treat Options Neurol.
Publication date / reference: 21/09/20. Carrillo-Larco et al. COVID-19 and Guillain-Barre Syndrome: a systematic review of case reports. Wellcome Open Res.
Summary: The authors aimed to evaluate the literature describing GBS in COVID-19 patients. Due to the early stage in the pandemic that this research was conducted (April 22nd 2020), the authors had to rely on case reports due to the lack of more robust literature at that point in time. The literature search detected eight reports, including 12 patients, of GBS in COVID-19. The presentation of GBS relative to the onset of COVID-19 symptoms was variable (5-24 days), as were the outcomes of patients. Five patients had favourable evolution, four remained with relevant symptoms or required critical care and one died. It would be interesting to ascertain the state of GBS COVID-19 literature at the current point in the pandemic.
Publication date / reference: 06/10/20. Pujhari et al. Clotting disorder in severe acute respiratory syndrome coronavirus 2. Rev Med Virol.
Publication Date/Reference: 5/10/20 Amir Soheil Tolebeyan et al. Headache in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Narrative Review. Headache.
Summary: This narrative review by Tolebeyan et al. summarises literature concerning headache as a manifestation of coronavirus, and aims to investigate the pathophysiological connection between headache and SARS-COV-2.
Publication date / reference: 21/09/2020. Carillo-Larco et al. COVID-19 and Guillain-Barre Syndrome: a systematic review of case reports. Wellcome Open Res.
Summary: Systematic review of case reports of 12 patients with GBS and COVID-19, including one Miller Fisher case. The data suggests that GBS occurs after COVID-19 onset. CSF samples of all patients tested negative for SARS-CoV-2. The authors also highlight that comparison with GBS patients in the context of another viral outbreak (Zika), revealed similarities and differences that may warrant further research.
Publication date / reference: 10/09/20. Misha and Banerjea. Neurological Damage by Coronaviruses: A Catastrophe in the Queue!. Front. Immunol.
Publication date / reference: 01/10/20. Pantelis et al. Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19. Aust N Z J Psychiatry.
Publication date / reference: 01/10/20. De Sire et al. Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review. Update as of August 31st, 2020. Eur J Phys Rehabil Med.
Publication date / reference: 25/09/20. Alquisiras-Burgos et al. Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection. Mol Neurobiol.
Publication date / reference: 25/09/20. Finsterer et al. SARS-CoV-2 associated Guillain-Barre syndrome in 62 patients. Eur J Neurol.
Publication date / reference: 24/09/20. Glezer et al. Viral infection and smell loss: The case of COVID-19. J Neurochem.
Publication date / reference: 22/09/20. Mo et al. The prognosis and prevention measures for mental health in COVID-19 patients: through the experience of SARS. Biopsychosoc Med.
Publication date / reference: 21/09/20. Tisdale et al. Neuro-ophthalmic manifestations of coronavirus disease 19. Curr Opin Ophthalmol.
Publication date / reference: 16/09/20. Dey et al. Neuroinvasion of SARS-CoV-2 may play a role in the breakdown of respiratory center of the brain. J Med Virol.
Publication date / reference: 15/09/20. Roberto et al. Electroencephalographic findings in COVID-19 patients: A systematic review. Seizure.
Publication date / reference: 10/09/20. Rahman et al. Neurological manifestations in COVID-19: A narrative review. SAGE Open Med.
Publication date / reference: 21/08/20. Gomes de Assis et al. Respiratory Syndrome Coronavirus Infections: Possible Mechanisms of Neurological Implications-A Systematic Review. Front Neurol.
Publication date / reference: 21/08/20. Wenting et al. COVID-19 Neurological Manifestations and Underlying Mechanisms: A Scoping Review. Front Psychiatry.
Publication date / reference: 18/09/20. Calderon-Garciduenas et al. Environmental Nanoparticles, SARS-CoV-2 Brain Involvement, and Potential Acceleration of Alzheimer’s and Parkinson’s Diseases in Young Urbanites Exposed to Air Pollution. J Alzheimers Dis.
Publication date / reference: 17/09/20. Vohora et al. COVID-19 and seizures: Is there a link? Epilepsia.
Summary: The authors conducted a systematic search for studies of neurological complications of COVID-19, with a particular focus on epilepsy. They found no case or study yet reported to justify any direct relation between the potentiation of epileptic seizures and COVID‐19.
Publication date / reference: 16/09/20. Al-Sarraj et al. The spectrum of neuropathology in COVID-19. Review Neuropathol Appl Neurobiol
Summary: This is a comprehensive narrative review of neuropathological findings in COVID-19, which included primary data from the authors’ autopsy findings. Based on the findings of 81 reported brain autopsy studies, the authors found no specific pathophysiological findings. From their series of eight autopsied patients, recent ischaemic brain changes and microglial activation were most commonly found. These were likely due to a combination of diffuse lung damage, multiple organ failure and the physiological consequence of being on a ventilator. However, the clinical characteristics of the sample were not reported so these pathological findings cannot be attributed to given clinical deficits. In their study, and the majority of studies in their review, SARS-CoV-2 was not detected in autopsied brain samples. However, this does not rule out the potential of direct viral neurotropism. The immunohistochemistry and RT-PCR techniques may be unable to detect viral material in very small quantities. Additionally, the preparation of post-mortem tissue could affect the detectability of the virus. More detailed work including large numbers of autopsy brain examinations correlated with clinical, laboratory and imaging data are needed.
Publication date / reference: 16/09/20. Zahra et al. Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19? Brain Behav.
Summary: The authors conducted a systematic literature search and narrative review aiming to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID‐19. From 23 included articles on 12314 patients, the authors offer the not-unsurprising conclusion that “COVID‐19 patients frequently report symptoms of anosmia and dysgeusia, and therefore, these symptoms should raise a high index of suspicion for COVID‐19 infection”. It is perhaps harder to draw more specific take-away messages, due to a wide variance of reported frequency, severity, and outcome. Interestingly there was some evidence that OTD is significantly more common in younger patients and those who are female. There was a high risk of reporting bias as most studies utilized self‐report questionnaires, however.
Publication date / reference: 15/09/20. Paliwal et al. Neuromuscular presentations in patients with COVID-19. Neurol Sci.
Summary: This literature review focussed on the neuromuscular manifestations of COVID-19. The authors performed an extensive search of PubMed, Google Scholar, Scopus and preprint databases. By utilising case reports, case series and cohort studies the demographic, clinical, CSF and neuroimaging characteristics of COVID-19 patients presenting with peripheral nervous system manifestations. In terms of myalgia, prevalence estimates sit at around 35.8% in those infected with SARS-CoV-2 infection. Myositis and rhabdomyolysis were reported in nine case reports, eight of which presented with generalised or limb weakness. In addition to myositis and rhabdomyolysis, one report identified six COVID-19 patients with critical-illness myopathy, manifesting as acute flaccid quadriparesis. Six patients with COVID-19 related neuropathy were also identified. Cranial neuropathies also continue to be described, albeit seldomly, following SARS-CoV-2 infection. The authors presented a potential pathological mechanism for neuromuscular disorders in COVID-19 and concluded that SARS-CoV-2 might have the ability to directly infect nerve cells or impact on function via “molecular mimicry”.
Publication date / reference: 14/09/20. Orru et al. Neurological Complications of COVID-19 and Possible Neuroinvasion Pathways: A Systematic Review. Int J Environ Res Public Health.
Summary: The authors systematically reviewed the neurologic complications of COVID-19 in CNS and PNS. The limited search strategy (Pubmed and Scopus, only seven terms) may partly explain why they found only 87 studies even searching as late as June 2020 and of which 65 were case reports. Due to this design it is hard to interpret the frequency estimates reported by the authors, who call for the adoption of case-control designs in future study protocols.
Publication date / reference: 15/09/20. Yamamoto et al. COVID-19: Review of a 21st Century Pandemic from Etiology to Neuro-psychiatric Implications. J Alzheimers Dis.
Summary: In this wide-scoping systematic review, the authors provide a comprehensive overview of the wide effects of COVID-19, including the neuropsychiatric implications.
Publication date / reference: 11/09/20. Lee et al. A systematic review of the neuropathologic findings of post-viral olfactory dysfunction: implications and novel insights for the COVID-19 pandemic. Am J Rhinol Allergy.
Summary: The authors of this systematic review searched PubMed and Embase for primary data on olfactory dysfunction secondary to viral infection and uncovered 38 animal studies and 7 human studies. Study design, experimental model and outcome measured varied greatly. It was also observed that viral effects on the olfactory system varied significantly based on viral substrain but tended to consist of damage or alteration in components of the olfactory epithelium and/or the olfactory bulb.
Publication date / reference: 25/08/20. Florez-Perdomo et al. Relationship between the history of cerebrovascular disease and mortality in COVID-19 patients: A systematic review and meta-analysis. Clin Neurol Neurosurg.
Summary: The authors conducted a systematic search and narrative review of the impact of a history of previous cerebrovascular disease (CVD) on mortality in COVID-19. Extending until May 2020, they found seven eligible retrospective observational studies reporting mortality from COVID19 which also included data on a history of CVD. From the 3244 patients included in these studies, 198 had a history of CVD. These patients had higher mortality from COVID-19 (OR 2.78, 95%CI [1.4–5.5]). Limitations include the small number of patients with a history of CVD, and that most of the studies were carried out early in the course of the pandemic in China. The authors conclude that while prior CVD may predict poorer outcomes, prospective studies are needed to confirm cerebrovascular disease as a risk factor for COVID-19 mortality.
Publication date / reference: Sep 2020. Suri et al. COVID-19 pathways for brain and heart injury in comorbidity patients: A role of medical imaging and artificial intelligence-based COVID severity classification: A review. Comput Biol Med.
Publication date / reference: Fridman et al. Stroke Risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases. Neurology.
Summary: The authors conducted a systematic review of stroke in patients with COVID-19 and included in their analysis original data from a cohort of unpublished patients. The prevalence of stroke was 1.8% (including 10 published studies, total n=3306), of which 1.5% were ischaemic. In-hospital mortality, assessed from a total of 43 studies (including case reports, total n=160), was 34.4%. A cluster analysis was used to assess which patient groups were at greatest risk of mortality. The following phenotype was associated with a three times greater risk of death: older age, greater burden of comorbidities and severe COVID-19 respiratory symptoms. Of these factors, the severity of COVID-19 respiratory symptoms had the strongest association with stroke mortality. Looking at the younger cohort (<50 years old) of patients with stroke, nearly half of them presented to hospital with stroke, before the onset of any respiratory symptoms. These results add value in attempting to stratify who is at greatest risk from stroke and which factors can be used to predict outcome following stroke in patients with COVID-19.
Publication date / reference: 10/09/20. Stafstrom and Jantzie. COVID-19: Neurological Considerations in Neonates and Children. Children (Basel).
Publication date / reference: 08/20. Pranata et al. Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression. J Stroke Cerebrovasc Dis.
Summary: This is a systematic review and meta-analysis which evaluated the effect of cerebrovascular and cardiovascular disease on outcome of patients with COVID-19. Based on the pooled effects of 16 studies (total n=4448), both cerebrovascular and cardiovascular diseases were associated with poorer outcome and increased mortality. Meta-regression analysis showed that the effect of cerebrovascular disease on outcome was not affected by cardiovascular disease and vice versa. The associations were not influenced by gender, age, hypertension, diabetes and respiratory comorbidities.
Publication date / reference: 10/09/20. Panda et al. Neurological Complications of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis. J Trop Pediatr.
Summary: This is a systematic review and meta-analysis of neurological complications in children with COVID-19. The authors included 21 studies and five case reports (total n=3707) in their analysis. Similar to adult cohorts, non-specific neurological symptoms were common – headache, myalgia and fatigue were found in 16.7% of cases. Whereas, a minority (n=42, 1%) had serious nervous system complications including encephalopathy, seizures and meningism. As in adult populations, these complications were associated with more severe COVID-19 disease. There were a paucity of reports of intracranial haemorrhage, cranial nerve palsy, GBS and visual changes.
Publication date / reference: 11/09/20. Viani-Walsh et al. Vitamin D deficiency in schizophrenia-implications for COVID-19 infection. Ir J Psychol Med.
Publication date / reference: 29/08/20. Pan et al. Neuroradiological features of mild and severe SARS-CoV-2 infection. Acad Radiol.
Summary: The authors of this systematic review conducted a literature search on PubMed and Embase for studies reporting CT or MRI neuroimaging findings in patients with confirmed COVID-19. 61 studies including a total of 711 patients were assessed. In patients with mild respiratory symptoms the most common neuroradiological findings were cranial nerve abnormalities, ischaemic infarction and white matter abnormalities, whilst in patients with severe respiratory symptoms the most common findings were white matter abnormalities, ischaemic infarction and haemorrhagic events.
Publication date / reference: 08/09/20 Ong et al. Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications Mol Neurobiol.
Publication date / reference: 29/08/2020 Patel et al. Age-Adjusted Risk Factors Associated with Mortality and Mechanical Ventilation Utilization Amongst COVID-19 Hospitalizations-a Systematic Review and Meta-Analysis. N Compr Clin Med.
Summary: Systematic review and meta-analysis of 29 papers examining risk factors for mortality and mechanical ventilation in COVID-19. Pre-existing cerebrovascular disease showed association with mortality (r = 0.35) and use of mechanical ventilation (r = 0.29) in pooled analysis.
Publication date / reference: 29/08/20. Emmerton & Abdelhafiz. Delirium in Older People with COVID-19: Clinical Scenario and Literature Review. SN Compr Clin Med.
Publication date / reference: 18/08/20 Tariku et al. Available Evidence and Ongoing Hypothesis on Corona Virus (COVID-19) and Psychosis: Is Corona Virus and Psychosis Related? A Narrative Review. Psychol Res Behav Manag.
Summary: The authors conducted a systematic search and narrative review of psychosis manifestations in patients with COVID-19. The literature search yielded minimal results, including a total pool of only ten patients. Four of the patients had a prior history of mental illness (not further described). In most of these patients, the manifestation was predominant hallucinations and delusions which followed an acute course and improved with antipsychotic medication. The physical health of these patients was not reported and it is important to ascertain the severity of COVID-19 disease in this population. Further research is required to understand psychotic manifestations in this new disease.
Publication date / reference: 13/08/20. Johnson et al. Pulmonary and Extra-Pulmonary Clinical Manifestations of COVID-19. Front Med.
Publication date / reference: 12/08/20. Battaglini et al. Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings. Front Neurol.
Summary: The authors provide a non-systematic updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiology of brain-lung interactions, and suggest strategies to optimise respiratory support in critically ill patients with SARS-CoV-2 pneumonia.
Publication date / reference: 19/09/20. Iadecola et al. Effects of COVID-19 on the Nervous System. Cell.
Publication date / reference: 03/09/20. Levine et al. Studying the neuropsychological sequelae of SARS-CoV-2: lessons learned from 35 years of neuroHIV research. J Neurovirol.
Publication date / reference: 02/09/20. Rahimi. Guillain-Barre syndrome during COVID-19 pandemic: an overview of the reports. Neurol Sci.
Summary: The author of this review performed a search of the literature on SCOPUS, PubMed, Embase, Cochrane database, Google Scholar and Ovid and found that at the time of writing, 31 cases of Guillain-Barre syndrome (GBS) associated with COVID-19 had been reported. GBS symptoms started on average 11.92 days after infection with SARS-CoV-2, mean age of 26 patients was 57.26 and the most common subtype of GBS reported was acute inflammatory demyelinating polyneuropathy.
Publication date / reference: 31/08/20. Kumar et al. Possible routes of SARS-CoV-2 invasion in brain: In context of neurological symptoms in COVID-19 patients. J Neurosci Res.
Publication date / reference: 29/07/20. Ftiha et al. Neurological symptoms due to Coronavirus disease 2019. Neurol Int.
Publication date / reference: August 2020. Sulzer et al. COVID-19 and possible links with Parkinson’s disease and parkinsonism: from bench to bedside. NPJ Parkinsons Dis.
Publication date / reference: 07/08/20. Sharifian-Dorche et al. Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic. J Neurol Sci.
Summary: In this systematic review, Sharifian-Dorche and colleagues summarised the evidence regarding the effects of different coronaviruses on the nervous system and described the range of reported neurological complications of COVID-19. 225 studies relating to the neurological complications of coronavirus infections, with 208 being pertinent to COVID-19. The authors found similarities between the neurological complications of SARS-Cov-1, MERS-CoV and COVID-19. The most common neurological complications of COVID-19 were anosmia, ageusia, and headache. More serious complications of COVID-19 have been reported including stroke, impairment of consciousness, seizures and encephalopathy.
Publication date/reference: 01/09/2020. Mohammadi et al. Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms. Mol Neurobiol.
Summary: In this review article, Mohammadi and colleagues review the current evidence regarding immunological pathways which potentially contribute to the development of neurological complications in COVID-19. Mohammadi and colleagues propose that COVID-19 aberrant immune response mediated by SARS-Cov-2 is responsible for the majority of neurological complications of COVID-19, increasing the risk of Alzheimer’s disease, Parkinson’s disease, stroke, MS, GBS, seizure and brainstem involvement through immune pathways including cytokine storm, autoimmunity, microglial and inflammasome activation, gut microbiome modulation, WBC infiltration into the CNS, inflammatory-mediated vascular wall injury and upregulation of pro-coagulative factors.
Publication date / reference: 26/08/20. Kaseda & Levine. Post-traumatic stress disorder: a differential diagnostic consideration for COVID-19 survivors. Clin Neuropsychol.
Summary: In this narrative review, Kaseda and Levine reviewed literature regarding the psychiatric, neurological and neuropathological outcomes of patients with SARS and MERS; neurological outcomes in COVID-19 survivors; PTSD associated with procedures common to COVID-19 patients. There is evidence to suggest that MERS and SARS survivors are at increased risk of PTSD, however, there is little evidence regarding the risk of PTSD in patients with COVID-19. PTSD is known to occur in patients who have been in ICU, been intubated and in those who have experienced delirium. Research in patients with PTSD in the context of mild traumatic brain injury may account for patient’s subjective cognitive complaints and neuropsychological test performance.
Publication date / reference: 24/08/20. Hogan et al. COVID-19 in Patients With Seizures and Epilepsy: Interpretation of Relevant Knowledge of Presenting Signs and Symptoms. Epilepsy Curr.
Summary: This review provided a focussed summary of pertinent clinical diagnostic information about the neurological involvement of SARS-CoV-2, especially in relationship to patients with seizures and epilepsy. The authors reported that seizures in epilepsy are multifactorial in origin, and SARS-CoV-2 CNS invasion may therefore not directly be related to exacerbations. They also highlighted the importance of recognising that neurological complications most commonly occur in severe cases. The authors also reported that there is no conclusive evidence from cohort studies that seizures due to epilepsy are worsened in COVID-19. The authors called for further studies evaluating COVID-19 patients with epilepsy and the frequency/severity of seizures.
Publication date / reference: 24/08/20. Khatoon et al. Neurological manifestations of COVID-19: available evidences and a new paradigm. J Neurovirol.
Summary: Non-systematic narrative review of the usual topics of potential neurotropism and neurological manifestations, but with an added approach. The authors used a series of publicly available online databases and types of network analysis to examine a list of 331 human genes previously shown to interact with SARS-CoV-2 protein, with 73 of these genes recorded as showing expression in the brain. With these ‘in silico’ methods they identified a hypothesised protein-protein interaction network of brain genes that may also interact with SARS-CoV-2. They continued further to discuss known associations between these genes and brain disease. The authors did not validate any of these analyses with experimental work; rather the study presents a series of hypotheses.
Publication date / reference: 04/08/20. Alomari et al. COVID-19 and the central nervous system. Clin Neurol Neurosurg.
Summary: In this narrative review, Alomari and colleagues presented a broad array of evidence concerning nervous system associations with COVID-19. They reviewed the potential routes of SARS-CoV-2 into the nervous system (including the viral spike protein and ACE-2R affinity) and non-neuroinvasive mechanisms underlying COVID-19 neurological complications. The authors also presented the interesting mechanistic evidence including CSF and neuroimaging studies.
Publication date / reference: 04/08/20 Vernuccio et al. Thromboembolic complications of COVID-19: the combined effect of a pro-coagulant pattern and an endothelial thrombo-inflammatory syndrome. Clin Radiol.
Summary: This review aimed to illustrate thromboembolic complications directly or indirectly related to COVID-19 disease. The authors highlighted the haemostatic abnormalities found in some COVID-19 patients, including thrombocytopenia, elevated D-dime, increased clot strength and hyperfibrinogenaemia. In particular, such abnormalities increase the risk of death in these patients. A further suggestion as to the origin of the pro-thrombotic state in COVID-19 is offered in the form of a progressive endothelial thrombo-inflammatory syndrome causing microvascular disease. The authors presented a case for the use of radiological imaging in diagnosing thrombotic complications in SARS-CoV-2 infection. They argued that patients admitted to ICU should routinely have CT pulmonary angiography performed, particularly if D-dimer levels are raised, due to the high prevalence of pulmonary embolisms in COVID-19. The authors concluded that the rate of thromboembolic complications in COVID-19 patients is relatively high, and therefore imaging may be of use for identification of complications, such as ischaemic stroke, PE, acro-ischaemia and mesenteric ischaemia.
Publication date / reference: 08/07/2020. Ahmadirad and Ghasemi. COVID-19 and central nervous system: entry routes and probable damages. Basic Clin Neurosci.
Summary: This narrative review by Ahmadirad and Ghasemi and discuss the neurotropism and CNS complications of SARS-Cov-2.The authors discuss that SARS-Cov-2 enters the CNS through olfactory neurons and that the effect of hypoxia on the CNS may be responsible for some of the neurological complications associated with COVID-19.
Publication date / reference: 01/07/2020. Mohebbi et al. Drug Interactions of Psychiatric and COVID-19 Medications. Basic Clin Neurosci.
Summary: The authors report a systematic search and narrative review of pharmacokinetic drug-drug interactions between psychotropic medications and antiviral COVID-19 medications. From 30 studies they provide a detailed review of the reported literature – the CYP450 properties of 30 separate psychiatric drugs or drug classes are discussed. The main limitation is the lack of experimental data in actual COVID-19 patients: the proposed interactions are historical and mainly speculative in the context of a multisystem disorder like COVID-19. Nonetheless this paper may be helpful especially for liaison psychiatrists or doctors working with moderate-severe COVID patients in settings where antiviral drugs may be considered.
Publication date / reference: 25/08/2020. Abu-Rumeileh et al. Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. J Neurol.
Summary: The authors of this systematic review searched the literature up until July 20th 2020 and included 73 patients across 52 papers. Patients were predominantly male (68.5%) with a mean age of 55. Most patients displayed respiratory symptoms with or without systemic symptoms and developed GBS after COVID-19. Subtype of GBS was most commonly classic sensorimotor form and acute inflammatory demyelinating polyneuropathy. CSF albuminocytological dissociation was present in 71% of cases and CSF SARS-CoV-2 RNA was not present in those tested. Over 70% of patients displayed a good prognosis, generally following treatment with intravenous immunoglobulin, and poorer outcome was associated with significantly older age as per previous findings for both GBS and COVID-19.
Publication date / reference: 27/08/2020. Almqvist et al. Neurological manifestations of coronavirus infections – a systematic review. Ann Clin Transl Neurol.
Summary: The authors report a high quality systematic search of the neurology of coronavirus infections, extending to 26th July. They synthesised 378 studies (327 of which were about SARS-CoV-2). They narratively review neurological symptomatology and complications, fluid biomarkers, and neuropathology. The authors conclude by urging vigilance for at least ﬁve classes of neurological or neuropsychiatric complications: (1) cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as GBS and ADEM, (4) (meningo-)encephalitis, potentially with concomitant seizures, and (5) mood disorders or psychosis.
Publication date / reference: 09/20. Correia et al. Neurological manifestations of COVID-19 and other coronaviruses: A systematic review. Neurol Psychiatr Brain Res.
Summary: The authors report a systematic search of neurological manifestations of COVID-19 extending until April 10th, and which therefore is outdated. Only seven studies are included: compare this with 327 in another review published this week.
Publication date / reference: 02/08/20. Nieto et al. The quality of research on mental health related to the COVID-19 pandemic: a note of caution after a systematic review. Brain Behav Immun Health.
Summary: The authors of this pre-registered PRISMA protocol compliant systematic review identified 28 papers on mental health related to the COVID-19 pandemic. They noted a widespread use of convenience samples and a lack of a priori power analysis together with low compliance with open science recommendations (such as study pre-registration and database availability), all of which the authors felt raised concerns regarding validity, generalisability and reproducibility of their findings.
Publication date / reference: 27/08/20. Schirinzi et al. COVID-19: dealing with a potential risk factor for chronic neurological disorders. J Neurol.
Publication date / reference: 24/08/20 Sachdev ert al., Neurological manifestations of COVID-19: A brief review. Indian J Med Res
Publication date / reference: 25/05/20. Sinanović et al. COVID-19 Pandemia: Neuropsychiatric Comorbidity and Consequences. Psychiatr Danub.
Summary: In this narrative review, Sinanović and colleagues gave an overview of neurologic and psychiatric findings in patients with COVID-19 (up to May). Reports of common neurological findings, including headache and impaired consciousness were described as were the worrying rates of delirium and encephalopathy in this population. In their conclusion, the authors implied that the neuropsychiatric findings were due to CNS invasion by SARS-CoV-2, however, evidence of viral detection in post-mortem brain tissue or in CSF was not presented and remains a controversial area.
Publication date / reference: 01/04/20. Butala. Neurological Aspects of Coronavirus Infectious Disease 2019 (COVID-19). Innov Clin Neurosci.
Summary: A brief non-systematic narrative review discussing key issues in the neurology of COVID-19. The author covers SARS-CoV-2 neurotropism, frequency of neurological symptoms, the risk status of neurological patients, and national or institutional guidelines for managing COVID-19 in a range of neurological populations.
Publication date / reference: 19/08/20. Kaushik et al. Cross-Talk Between Key Players in Patients with COVID-19 and Ischemic Stroke: A Review on Neurobiological Insight of the Pandemic. Mol Neurobiol.
Summary: The authors conduct a non-systematic review of bidirectional associated risks between COVID-19 and stroke. Areas covered by discussion include the Renin-Angiotensin System, immunological responses, and the potential for cross-talk between COVID-19 and Stroke. There is a great deal of theory which remains to be tested.
Publication date / reference: 18/08/2020. Javelot et al. COVID-19 and its psychological consequences: Beware of the respiratory subtype of panic disorder. Respir Physiol Neurobiol.
Summary: Correspondence highlighting respiratory abnormalities in patients with panic disorder and panic attacks. The authors make the case that the current COVID-19 pandemic may lead to an increased cases of panic attack and panic disorder.
Publication date / reference: 21/08/20. Adamczyk-Sowa et al. Neurological symptoms as a clinical manifestation of COVID-19: implications for internists. Pol Arch Intern Med
Summary: In this comprehensive narrative review, Adamczyk-Sowa and colleagues reported the wealth of neurological manifestations of COVID-19. They made particular reference to reports of neurological abnormalities being the presenting feature of COVID-19 (e.g., meningoencephalitis) and the importance of altering internal medics to the varied presentation of this disease. The review also explored potential biomarkers of COVID-19 neurological involvement including the putative hypercoagulable state, indicated by deranged D-dimers, and the reported cytokine storm.
Publication date / reference: 21/08/20. Goldberg & Goldberg. Neuroradiologic manifestations of COVID-19: what the emergency radiologist needs to know. Emerg Radiol.
Summary: The authors review COVID-19 neurologic manifestations (with neuroradiologic correlates) which tend to present with more severe signs and symptoms. They discuss ischaemic stroke, intracerebral haemorrhage, thrombotic microangiopathy, inflammatory disease, acute haemorrhagic necrotizing encephalopathy, haemorrhagic posterior reversible encephalopathy syndrome, diffuse leukoencephalopathy and ADEM.
Publication date / reference: 08/08/20. Patel et al. Pre-existing cerebrovascular disease and poor outcomes of COVID-19 hospitalized patients: a meta-analysis. J Neurol.
Summary: The authors report a meta-analysis of the prevalence and outcomes of COVID-19 hospitalized patients with pre-existing cerebrovascular disease or stroke, with a search strategy running up to 30th April. From up to 11 studies (n=4987 confirmed cases of COVID-19) they found that pre-existing cerebrovascular disease among COVID-19 patients was associated with higher estimated odds of ICU admission, mechanical ventilation, and mortality. Meta-analysis showed that COVID-19 patient with pre-existing disease had higher odds of poor outcomes compared to better outcomes with a pooled OR of 2.67 (95% CI 1.75–4.06; p = 0.03). The authors acknowledged limitations including a lack of detail on type of CVD or stroke, severity, disability, and medications. They call for more studies, adjusted for risk factors and comorbidities with larger sample sizes dedicated to evaluating stroke burden.
Publication date / reference: 05/08/20. Abrams et al. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2: A Systematic Review. J Pediatr.
Summary: The purpose of this systematic review was to develop a comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to COVID-19. Based on eight studies of MIS-C (total n=440) the proportion of patients who tested positive for SARS-CoV-2 on RT-PCR was 13-69% and on serology it was 75-100%. The clinical presentation that was consistent across studies included fever with gastrointestinal, cardiovascular, and mucocutaneous manifestations. Elevated CRP, IL-6 and fibrinogen levels were observed in the majority, which suggests that a hyperinflammatory state is a hallmark of this syndrome. Interestingly, respiratory abnormalities were uncommon. These findings are limited by the heterogeneity of inclusion criteria used by individual studies, which to some extent reflects a lack of consensus regarding a diagnostic criteria for MIS-C.
Publication date / reference: 10/08/20 Janhardan et al. COVID-19 as a Blood Clotting Disorder Masquerading as a Respiratory Illness: A Cerebrovascular Perspective and Therapeutic Implications for Stroke Thrombectomy. J Neuroimaging.
Summary: A narrative review of SARS-CoV-2 and its thrombotic complications with particular emphasis on ischemic stroke. SARS-CoV-2 has been associated with multiple forms of thrombotic sequelae, from gut to pulmonary emboli, however the authors believe that rates of cerebrovascular thrombosis are lower and more variable (0.9-1.8%). In this review the authors explore the mechanisms underlying these thrombotic complications and warn of increased mortality in COVID-19 inpatients with ischaemic strokes (33% vs 14% without). In a detailed pathophysiological explanation, they demonstrate that COVID-19 strokes are more likely to be large vessel occlusions and more prone to re-thrombosis and re-occlusion.
Publication date / reference: 10/08/20. Yazdanpanah et al. Anosmia: a missing link in the neuroimmunology of coronavirus disease 2019 (COVID-19). Rev Neurosci.
Summary: Non-systematic primer in which the authors review COVID-19 associated anosmia. The article discusses the risk of mass hysteria, how the virus may enter olfactory cells, histopathological findings from the olfactory epithelium, and the likelihood of CNS involvement, and neuroimmunological hypotheses.
Publication date / reference: 17/07/20 Coronavirus disease 2019 in children: Clinical & epidemiological implications Indian J Med Res.
Summary: This review describes transmission characteristics, clinical manifestations, diagnostic, treatment and preventive aspects of COVID-19 in children compared to adults. Although all grades of severity exist in children, the majority only develop mild illness which emphasizes the need for conducting studies to understand the protective mechanisms in children as this has significant implications for the development of future therapeutics. The authors highlight paediatric groups which may be most at risk those with contact with severe COVID-19 cases, underlying health conditions, long-term immunosuppressants, and infants under three months. The authors highlight avenues for future systematic research to address the gap in knowledge of COVID-19 in children;. focusing on the extra-pulmonary and atypical clinical features, risk factors for severe illness, markers of severity, role of imaging, optimal supportive care and trials with newer therapies – antivirals and immunomodulatory drugs.
Publication date / reference: 13/08/20. Kolikonda et al. Association of Coronavirus Disease 2019 and Stroke: A Rising Concern. Neuroepidemiology.
Summary: This brief nonsystematic narrative review touches on main points of discussion in the relation of COVID-19 and stroke, including clinical studies proposing an association, putative viral neurotropism, and the impact of the pandemic on stroke care services.
Publication date / reference: 01/08/20 Tiziano Di Carlo et al. Exploring the clinical association between neurological symptoms and COVID-19 pandemic outbreak: a systematic review of current literature. J Neurol.
Summary: This systematic review included 19 studies (n=12,157) involving confirmed COVID-19 patients. PubMed and Ovid EMBASE were searched in accordance with PRISMA guidelines. Neurological symptoms were categorised into three groups: Central nervous system (CNS) manifestations, peripheral nervous system manifestations and muscular injury manifestations. Data from the population was divided into severe and non-severe groups. Among CNS symptoms, olfactory (46.8%) and gustatory (52.3%) malfunctions were most common. Both CNS and muscular injury symptoms were significantly more common among severe patients (dizziness: 20.1% vs 10.5%; headache: 13% vs 8%; skeletal muscle injury: 29.4% vs 11.8%). The authors concluded that their review revealed a wide spectrum of neurological complications in hospitalised patients with laboratory-confirmed SARS-CoV-2 infection.
Publication date / reference: 01/08/20 Agyeman et al. Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis. Mayo Clin Proc.
Summary: The authors of this PRISMA protocol concordant systematic review searched MEDLINE, EMBASE and MedRxiv, and ultimately included 24 studies (n = 8438) which reported olfactory and gustatory dysfunction in test-confirmed COVID-19 patients. 41% and 38.2% of patients were found to have olfactory dysfunction and gustatory dysfunction respectively. Older age was seen to correlate significantly with reduced prevalence of both olfactory and gustatory dysfunction. Studies using objective measurement noted a significantly higher prevalence of olfactory dysfunction than those using self-reported dysfunction.
Publication date / reference: 31/07/20. Pennisi et al. SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms. Int J Mol Sci.
Summary: In this review, Pennisi and colleagues conducted a systematic literature search of nervous system manifestations of COVID-19. From the 23 included studies, the authors found that headache, taste/smell disturbance and encephalopathy were commonly reported amongst the neurological complications. The authors critiqued potential neuroinvasive mechanisms underlying SARS-COV-2 including haematogenous versus trans-synaptic viral propagation. The authors made the important point that the current literature base is dominated by case reports/series and retrospective research.
Publication date / reference: 05/08/20. De Sanctis et al. Guillaine Barré syndrome associated with SARS-CoV-2 infection. A systematic review. Eur J Neurol.
Summary: The authors of this PRISMA protocol compliant systematic review conducted a search for original case reports or case series of patients diagnosed with Guillaine Barré syndrome (GBS) who had tested positive for SARS-CoV-2 infection. They were only able to identify 13 eligible case reports and one case series (n = 18). A range of -8 to 24 days between onset of COVID-19 and GBS symptoms was noted though only five patients displayed an overlap of these symptoms. Overall GBS symptomatology and clinical course in these patients was noted to not be dissimilar from that observed in GBS due to other etiologies, though the authors note that conclusions drawn are limited by the dearth of reported cases.
Publication date / reference: 06/08/20. Najjar et al. Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports. J Neuroinflammation.
Summary: In this comprehensive and detailed narrative review, Najjar and colleagues described the neurological and neuropsychiatric complications associated with COVID-19. Pathophysiological mechanisms were discussed including a maladaptive immune and hyperinflammatory response to SARS-COV-2 infection which could impair neurovascular endothelium, disrupt the BBB and induce parainfectious autoimmunity in the CNS through activation of signalling pathways. Evidence for direct neuroinvasive properties of SARS-COV-2 was also critiqued.
Publication date / reference: 06/08/20. Fatima et al. Impact of COVID-19 on neurological manifestations: an overview of stroke presentation in pandemic. Neurol Sci.
Summary: In this systematic review, Fatima and colleagues sought to determine the aetiology, risk factors and outcomes of patients with COVID-19 presenting with stroke. The authors summarised the results from six studies (total n=39) and found that conventional stroke risk factors were present in nearly all patients. Similar to background stroke data, the majority were ischaemic events (36/39), however half of the patients died. The cause of death was not reported in all studies and it is important to ascertain whether patients died from stroke or from respiratory disease. Prospective research is required to elucidate the prevalence and characteristics of stroke in patients with COVID-19.
Publication date / reference: 07/08/20. Samaranayake et al. Sudden onset, acute loss of taste and smell in coronavirus disease 2019 (COVID-19): a systematic review. Acta Odontol Scand.
Summary: This systematic review aimed to review the contemporary evidence on dysgeusia and anosmia as trigger prodromal symptoms in COVID-19 patients. Eight studies fulfilled the inclusion criteria (n=11,054). Sample sizes ranged from 69 to 10,069 patients. Anosmia and dysguesia symptoms were present in 74.9% and 81.3% ambulatory and hospitalised mild-to-severe COVID-19 cases, respectively. Olfactory and gustatory symptoms appeared prior to general COVID-19 symptoms in 64.5% and 54.0% respectively. The authors noted limitations of the review including that most of the included studies used self-report questionnaire data. They concluded that sudden, acute onset of anosmia or dysguesia could potentially be used in recognising SARS-CoV-2 infection.
Publication date / reference: 06/08/20. Orsini et al. Challenges and management of neurological and psychiatric manifestations in SARS-CoV-2 (COVID-19) patients. Neurol Sci.
Summary: Orsini and colleagues conducted a systematic literature search of neurological and psychiatric manifestations of COVID-19. In addition to reviewing the reported neurological and psychiatric symptoms in this population, the authors focused on pharmacological interactions and potential neurological side effects of COVID-19 treatments. They provided an extensive overview of neuropsychiatric medication interactions with nine repurposed drugs used to treat COVID-19. Additional attributes of this review included a section on the paediatric population, where fewer reports of neurological complications have emerged. Future directions for research were highlighted including the need for proper documentation of neuropsychiatric findings and use of autopsy in patients with such complications.
Publication date / reference: 29/07/20. Nazari et al. Central Nervous System Manifestations in COVID-19 Patients: A Systematic Review and Meta-analysis. MedrXiv (preprint).
Summary: Another meta-analysis of CNS manifestations of COVID-19 (64 studies, 11282 patients), again limited to late April 2020, and again finding that headache (8.7%) is the most common symptom specific to the CNS, followed by dizziness (5.9%) and impaired consciousness (1.9%).
Publication date / reference: 30/07/20. Steardo Jr et al. Psychiatric face of COVID-19. Transl Psychiatry.
Summary: Narrative review summarising psychiatric aspects of COVID-19. The authors adopt the position that the neurotropism of SARS-CoV-2 is well established, although this remains debatable, and the narrative omits to highlight the many reported cases in which viral infection is not shown in the CNS. There is also something of a pattern whereby hypotheses extrapolated from earlier literature are presented in the manner of facts (e.g., “The impact of SARS-COV-2 infection on the brain is associated with excessive physical and psychological stress that stimulates the hypothalamic-pituitary-adrenal axis thus further exacerbating neuroinflammatory status” – a prediction which cites a study in 2016 but which has no such evidence for SARS-CoV-2). Careful reading is advised as the paper discusses earlier mechanistic literature on a wide range of interesting topics, including depression, bipolar disorder, psychosis, epilepsy, PTSD, and schizophrenia, indirectly inviting a somewhat premature extrapolation to COVID-19. The truth, as the authors concede, is that “there are few preliminary studies considering neuropsychiatric complications of COVID-19” but the paper is nevertheless an interesting primer to possible areas of future study.
Publication date / reference: 20/07/20. Ostuzzi et al. Pharmacological treatment of hyperactive delirium in people with COVID-19: rethinking conventional approaches. Ther Adv Psychopharmacol.
Summary: Systematic search and narrative review of RCTs testing the pharmacological treatment of delirium or agitation related to dementia or psychosis, with the aim of deriving therapeutic options for the management of delirium in COVID-19. The authors acknowledged up-front the “notable limitations” in comparing data from such different populations. They argued that pragmatically, similar medications are often used for agitation “irrespective of the underlying aetiology”: readers must make their own judgement on this. They found that only quetiapine and dexmedetomidine showed benefits over placebo for the treatment of delirium in ICU settings, while no medications had evidence of benefit over placebo in non-ICU settings. In all cases sedation, anticholinergic effect, QTc prolongation and interactions with anti-COVID treatments should be carefully weighed on a case-by-case basis.
Publication date / reference: 16/06/20. Lennon. Neurologic and Immunologic Complications of COVID-19: Potential Long-Term Risk Factors for Alzheimer’s Disease. J Alzheimers Dis Rep.
Summary: This narrative review aimed to discuss the findings related to neurological complications of COVID-19, the impact of bio-immunology and psychosocial stressors and the importance of considering neurodegenerative sequelae of COVID-19. The authors highlighted the question as to whether or not patients will be at higher risk of developing neurodegenerative disorders such as Alzheimer’s following recovery? COVID-19 symptoms are discussed in context, such as findings from previous studies, including olfactory dysfunction being associated with the graduation from mild cognitive impairment to Alzheimer’s disease. Multiple risk factors for Alzheimer’s are mentioned, with a case presented for their consideration, instead of solely utilising age as a predictor of neurodegenerative morbidity following SARS-CoV-2 infection. The authors conclude that conclusions should not be jumped to, until longitudinal studies are completed.
Publication date / reference: 25/07/20. Pero et al. COVID-19: A Perspective from Clinical Neurology and Neuroscience. Neuroscientist.
Summary: In this narrative review, Pero and colleagues succinctly described the current state of evidence of COVID-19 related neurological findings and putative pathophysiological mechanisms. They also discussed the possibility of long-term neurological effects of COVID-19, particularly with regard to the effects of other coronaviruses and the chronic sequelae of neuroinflammation. Long-term, prospective follow-up studies are required to understand the long-term effects of this virus on the nervous system.
Publication date / reference: 28/07/20. Riederer and Meulen. Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses. J Neural Transm (Vienna).
Summary: In this comprehensive narrative review, the authors described the reported spectrum of neurological and neuropsychiatric COVID-19 symptoms. They also presented evidence form previous pandemics (spanish influenza) and HIV-dementia in warning the reader of potential long-term neuropsychiatric effects of COVID-19. The main conclusions of this review were to stress the importance of a multimodal approach to understanding the effect of this virus on the brain, specifically employing post-mortem brain analysis and long-term animal models infected with SARS-COV-2.
Publication date / reference: 28/07/20. Yachou et al. Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients. Neurol Sci.
Summary: The authors conducted a narrative review of studies exploring the neurological manifestations of COVID-19 and hypothesised mechanisms underlying these effects. Yachou and colleagues described the neuroinvasive properties of viruses (including HSV, VZV and previous coronaviruses) and presented the pathological similarities between SARS-COV-2 and known neuroinvasive viruses. Finally, the putative associations between viral infections and neurodegenerative diseases were explored in the context of MS, as a warning for the potential long-term neurological effects of this virus.
Publication date / reference: 27/07/20. Szcześniak et al. The SARS-CoV-2 and mental health: From biological mechanisms to social consequences. Prog Neuropsychopharmacol Biol Psychiatry.
Summary: In this narrative review, the authors described the potential neuropathological mechanisms of SARS-COV-2 and explored the relevance to mental health disorders in three populations (patients with COVID-19, general population and healthcare workers). Szcześniak and colleagues reviewed the evidence demonstrating first-episode psychosis in patients with COVID-19 (albeit mostly case reports), and the relatively stronger evidence of depression and anxiety in this population. Further research is required to elucidate the prevalence of longer-term impacts, such as PTSD, in patients with COVID-19. The authors also presented evidence that psychiatric patients could be more susceptible to COVID-19.
Publication date / reference: 30/7/20. Khan & Gomes. Neuropathogenesis of SARS-CoV-2 infection. Elife.
Summary: In this narrative review, the authors summarised recent research findings surrounding SARS-CoV-2 infection and neurological sequelae including encephalitis, stroke, anosmia and ageusia. They presented a round-up of the evidence detailing the detection of ACE2 receptors within the brain and thus a mechanism for the invasion of SARS-CoV-2 into neural matter and the CSF. The authors highlighted the potential exacerbating effect of SARS-CoV-2 infection in individuals with pre-existing neurological disorders such as Parkinson’s disease, indicating that the virus may be able to affect the brain in a variety of different manners. The authors then presented further possible mechanisms of neurological invasion by SARS-CoV-2, including haematogenous breach of the blood-brain barrier during cytokine storm, retrograde neuronal spread via the olfactory bulbs and neuroinvasion via intestinal vagal afferents.
Publication date / reference: 31/7/20. Potolache et al. Targetable Biological Mechanisms Implicated in Emergent Psychiatric Conditions Associated With SARS-CoV-2 Infection. JAMA Psychiatry.
Summary: This narrative review described the impact of serious infections and psychiatric outcomes. The evidence for CNS invasion by SARS-CoV-2 is discussed, including transport via olfactory and trigeminal nerves as well as the vagus nerves. The impact of severe illness courses vs mild illness courses on stress including fear of death and dying were discussed. The authors stated that severe trauma and post-traumatic stress disorder, which occur relatively commonly following SARS-CoV-2 infection, can induce robust pathophysiological abnormalities in the endocrine systems, which may further augment neuroimmune reactivity and induce pharmacological resistance in comorbid depression. The paper concludes by suggesting that history and clinical examination are of high importance to the treating clinician in COVID-19 induced psychiatric disorders. Additionally, advances in antiviral treatments and vaccines will not only prevent severe illness but benefit the brain and mental health.
Publication date / reference: 31/07/20. Morgello. Coronaviruses and the central nervous system. J Neurovirol.
Summary: In this narrative review, Morgello provided a comprehensive overview of CNS disease across seven coronaviruses, including the spectrum of reported clinical abnormalities and potential pathogenic mechanisms (making reference to animal models). Morgello also discussed associations between coronaviruses and chronic neurological disease, mainly MS.
Publication date/ reference: 21/07/20. Ferini-Strambi et al. COVID‑19 and neurological disorders: are neurodegenerative or neuroimmunological diseases more vulnerable? J Neurol
Summary: The authors conducted a non-systematic narrative review exploring SARS-CoV-2 infection among those with neurological conditions; the vulnerability to infection, potential to modify disease course and trigger future degeneration. The authors used the examples of Parkinson’s disease, Alzhiemer’s disease and Multiple Sclerosis (MS) to compare whether age could be decisive in neurodegenerative diseases whereas neuropathology may be critical in neuroimmunological diseases. This allowed them to highlight potential susceptible/protection factors for COVID-19 and stratify risk for neurodegeneration within this select research window. They tentatively suggest that Parkinson’s disease may be protective while those with MS may be at risk of more severe outcomes.
Publication date / reference: 20/07/20. Abdelaziz et al. Neuropathogenic human coronaviruses: A review. Rev Med Virol.
Summary: The authors conducted a non-systematic review of 25 cases (n=334) to explore the neurological and psychological sequelae of Human Coronaviruses, including SARS-CoV-2. They propose mechanisms for neurotropism and suggest that patients with pre-existing neurological disorders, such as multiple sclerosis or myasthenia gravis may be at increased risk of infection. There is limited exploration of the mechanisms underpinning these suggestions.
Publication date / reference: 16/07/20. Egbert et al. Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review. Brain Behav Immun.
Summary: The authors performed a review of 26 articles (including 21 case reports, and five cohort studies) relating to COVID-19 and brain abnormalities. They analysed the prevalence of neuroimaging abnormalities across the 124 patients with heterogeneous neurological manifestations (all PCR-confirmed), and found that white matter hyperintensities were most common, on MRI (66/124, 53%) and hypodensities on CT (29/124, 23%). The findings of this review are limited by the heterogeneity of the included studies, including the incorporation of case reports into their cumulative prevalence figures. Prospective and longitudinal research is required to understand the prevalence of neuroimaging abnormalities in patients with COVID-19.
Publication date / reference: 08/07/20. Divani et al. Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights. J Stroke Cerebrovasc Dis.
Summary: The authors conducted a non-systematic narrative review of recent research about the clinical manifestations and underlying potential pathophysiological stroke mechanisms in SARS-CoV-2 infection. The article is centred on the hypothesis that COVID-19 associated alterations in the renin-angiotensin system may consequently lead to imbalances in cerebral vasodilation, neuroinflammation, oxidative stress, and thrombogenesis, contributing to stroke pathophysiology.
Publication date / reference: 17/07/20. Silva et al. SARS-CoV-2: Should We Be Concerned about the Nervous System? Am J Trop Med Hyg.
Summary: The authors of this non-systematic narrative review aimed to explore neurological complications in patients with COVID-19 and to describe potential mechanisms of pathogenesis. Silva and colleagues described evidence of a range of respiratory viruses affecting the nervous system and compared structural and phenotypic similarities of these viruses to SARS-CoV-2. The authors posed the interesting comment that many of the putative pathogenic mechanisms reviewed (e.g., impaired blood–brain barrier and neuroinflammation) are reminiscent of the early stages of neurodegenerative disorders and could trigger this pathogenesis. Consequently, it is imperative to gather long-term follow-up data in these patients.
Publication date / reference: 20/07/20. Chen et al. A systematic review of neurological symptoms and complications of COVID-19. J Neurol.
Summary: The authors systematically reviewed 92 such studies extending to April 20th 2020. The most frequently-identified symptoms were headache, dizziness, smell or taste dysfunction and alterations in consciousness. The authors considered that the literature on cerebrovascular events and immune-mediated neurological diseases (among other complications) was “not suitable for quantitative analysis”, but this literature is rapidly growing, and it is unclear whether a search strategy extending to the present day would reach the same conclusion.
Publication date / reference: 21/07/20. Galassi & Marchioni. Facing acute neuromuscular diseases during COVID-19 pandemic: focus on Guillain-Barré syndrome. Acta Neurol Belg.
Summary: This review focussed on the state of current knowledge surrounding Guillain-Barré syndrome (GBS) both during and after infection with SARS-CoV-2. It discussed the association between COVID-19 and various acute neurological syndromes and the need for vigilance among clinicians. The paper examined the pathophysiological changes that may occur in the lungs as a result of ARDS with concomitant GBS pulmonary muscle dysfunction. The variable onset of neurological symptoms following viral infection reported in case reports was discussed. The authors concluded that future, large-scale trials are necessary in order to determine whether COVID-19 can trigger GBS, or is associated incidentally.
Publication date / reference: 22/07/20. Nazari et al. Central nervous system manifestations in COVID-19 patients: a systematic review and meta-analysis. MedRxiv (not peer reviewed).
Summary: The authors performed a PRISMA-compliant, PROSPERO-registered systematic review of 64 studies (n = 11,212) extending to April 20th, and reporting CNS symptoms in patients with COVID-19. Of reported central nervous system symptoms, headache was the most common with an incidence of 8.7%, whilst dizziness and impaired consciousness were less common with an incidence of 5.9% and 2.9% respectively. ‘Meta-analysis’ was conducted on 25 studies which reported mortality, with the authors reporting a pooled mortality incidence rate of 10.47% in patients with at least one central nervous system symptom, a rate which the authors argue is greater than that observed in the general infected population.
Publication date / reference: 23/07/20. Taherifard and Taherifard. Neurological complications of COVID-19: a systematic review. Neurol Res.
Summary: The authors conducted a PRISMA-compliant systematic review of neurological complications of COVID-19. From a broad inclusion criteria, they reviewed 22 studies and found that cerebrovascular disease was the most common COVID-19 complication, although quantitative data supporting this finding was not presented. The authors noted the presence of ischaemic stroke in young patients without significant risk factors and called for such patients to be routinely tested for COVID-19.
Publication date / reference: 24/07/20. Ceravolo et al. Rehabilitation and Covid-19: the Cochrane Rehabilitation 2020 rapid living systematic review. Eur J Phys Rehabil Med.
Summary: This is the first edition of a rapid systematic review started in April 2020 with the aim to gather and present the current evidence informing rehabilitation of patients with COVID-19 and/or describing the consequences due to the disease and its treatment. In this review, 36 out of 3703 studies were included. There was one cross sectional study, one historical cohort study and 12 case reports examined impairment in nervous system structures and related functions. The authors recommended all neurology patients presenting with symptoms changes to be tested for COVID. Specific recommendation pertaining to effective rehabilitation is limited by sparse, low quality evidence at present.
Publication date/reference: Preprint 25/07/20. Wildwing & Holt. Similarities between the neurological symptoms of COVID-19 and Functional Neurological Disorder: A systematic overview of systematic reviews and implications for future neurological healthcare services. Preprint MedRxiv.
Summary: This systematic overview isolated symptoms of functional neurological disorder (FND) from publicly available sources and qualitatively assessed 14 systematic reviews for neurological complications associated with COVID-19. 21 neurological outcomes were related to COVID-19, including some life-threatening emergencies such as stroke, haemorrhage and Guillain-Barré syndrome, which were subsequently excluded from the comparison. Thirteen remaining symptoms were noted also to be commonly present in FND, such as dizziness, fatigue, myalgia, anxiety and headache. The authors did not explicitly suggest that COVID-19 symptoms are a form of FND, instead highlighting that these symptoms may form an interesting area of interest for neuropsychiatry, raising awareness for FND.
Publication date / reference: 26/06/20. Ghasemiyeh et al. Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review. Ther Clin Risk Manag.
Summary: The authors conducted a narrative review of the potential for pharmacokinetic interactions between drugs used to treat COVID-19 and those used to treat stroke. They cautioned that cerebrovascular drugs (such as antiplatelets, antihypertensives, and oral anticoagulants) have potential major interactions with lopinavir/ritonavir and atazanavir in particular. They recommended careful monitoring of patients on chloroquine (CQ), hydroxychloroquine (HCQ), antiviral drugs, and/or corticosteroids, for cardiac arrhythmias, delirium, seizure, myopathy, or neuropathy.
Publication date / reference: 26/06/20. Abdullahi et al. Neurological and Musculoskeletal Features of COVID-19: A Systematic Review and Meta-Analysis. Front Neurol.
Summary: The authors conducted a systematic search up to April 17th 2020, identifying 51 studies for a meta-analysis of neurological and musculoskeletal features in patients with COVID-19. They reported a prevalence of 35% for smell impairment, 33% for taste impairment, 19% for myalgia, 12% for headache, 10% for back pain, 10% for dizziness, 3% for acute cerebrovascular disease, and 2% for impaired consciousness. Nearly all studies were retrospective but also regarded as methodologically “excellent” by the review authors.
Publication date / reference: 15/07/20. Collantes et al. Neurological manifestations in COVID-19 infection: A systematic review and meta-analysis. Can J Neurol Sci.
Summary: Via a systematic search extending to April 18th 2020, the authors identify 49 studies involving a total of 6,335 PCR-confirmed COVID-19 cases. They conducted a meta-analysis to estimate the point prevalence of headache, dizziness, nausea, vomiting, confusion, and myalgia. Only one study was prospective and 13 were case reports or series, illustrating the low methodological quality of the literature to date. Complications and laboratory findings were discussed in a more piecemeal approach, where data were available within the included studies.
Publication date / reference: 16/07/20. Bilinska & Butowt. Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism. ACS Chem Neurosci.
Summary: The authors review recent developments and propose a model for anosmia whereby “Sustentacular cells (SUSs) express ACE2 and are infected first. Impairment of SUS negatively affects olfactory receptor neurons (ORNs), inhibiting the odor perception cascade. Simultaneous rapid immune response is induced in a subset of ORNs and in microvillar cells. This triggers activation of lymphocytes and macrophages and their infiltration into the olfactory epithelium, as well as secretion of proinflammatory cytokines.” They speculate that separately, olfactory stem cell infection may explain why a small fraction of COVID-19 patients experience long-term dysosmia.
Publication date / reference: 17/07/20. Caress et al. COVID-19-Associated Guillain-Barre Syndrome: The Early Pandemic Experience. Muscle Nerve.
Summary: The authors reviewed reported cases of COVID-19 associated GBS identified via PubMed up to 22nd June 2020 (n=37 SARS-CoV-2 confirmed cases from 28 publications). Most reported cases were aged >50 years. The mean reported time to onset of neurologic symptoms was 11 days (range 3-28) from the onset of COVID-19, with a possible nadir on average 5 days later. Paraesthesia, pain, and weakness were the most common index neurological symptoms, and about one-third required mechanical ventilation. Details of diagnostic testing are provided in the subset of patients who received it. Most patients were treated with IVIG, and nearly all recovered. Long term outcomes were not well recorded. Conclusions are greatly limited by reporting bias, but provide a sense of the potential wide range of diagnostic test results in particular.
Publication date / reference: 16/07/20. Pouga. Encephalitic syndrome and anosmia in COVID-19: do these clinical presentations really reflect SARS-CoV-2 neurotropism? A theory based on the review of 25 COVID-19 cases. J Med Virol.
Summary: The author reviewed 25 cases of brain dysfunction (encephalopathy, encephalitis, meningitis, seizures, confusion) in patients with suspected or confirmed COVID-19, found via a Pubmed search extending to May 26th 2020. She found that while many authors presented their cases as SARS-CoV-2 (meningo)encephalitis, this diagnosis was speculative without any evidence of the virus within the CNS – nor even, often, PCR evidence of SARS-CoV-2 infection. A discussion follows of potential routes of neuroinvasion, in a narrative review format without new experimental data. The author closes by arguing for routine MRI in suspected cases of SARS-CoV-2 brain dysfunction.
Publication date / reference: 15/07/20 Alam et al. Severe acute respiratory syndrome coronavirus-2 may be an underappreciated pathogen of the central nervous system. Eur J Neurol.
Summary: Narrative review of the putative mechanisms used by SARS-CoV-2 to penetrate the CNS. The authors also speculate on the long-term effects of SARS-CoV-2 infection on the brain and in a potential for progression to neurodegenerative diseases, which have been noted in other human coronaviruses.
Publication date / reference: 15/07/20. Ostuzzi et al. Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations. BMC Med.
Summary: The authors present a ‘rapid review’ of 76 studies examining the safety of antidepressants, antipsychotics, anxiolytics, and selected anti-epileptic drugs on respiratory, cardiovascular, infective, immune, haematological, haemostatic, and neuropsychiatric functions. They found that psychotropic medications may present a range of safety issues in people with comorbidities also often seen in COVID-19. They attribute risk to both a COVID-related vulnerability and the potential interaction with off-label medical treatments used for COVID-19. Practical recommendations are given. This is an informative and carefully-conducted review presenting a large amount of helpful information and well worth a read.
Publication date / reference: 08/06/20. Gupta et al. Atypical Neurological Manifestations of COVID-19. Cureus.
Summary: This narrative review analysed 20 articles (searched between March-April of this year) pertaining to neurological manifestations of COVID-19. The authors analysed the neurological symptoms across all of the studies (n=1034 patients) and found, similar to other reports, that ageusia, anosmia and headache were the most common. This study has methodological limitations including a non-extensive search strategy and cannot easily be used to ascertain the prevalence of neurological features in COVID-19.
Publication date / reference: 23/06/20. Khateb et al. Coronaviruses and Central Nervous System Manifestations. Front Neurol.
Summary: This narrative review accumulated evidence of CNS involvement with general coronavirus infections. Pre-clinical and mechanistic evidence demonstrating putative mechanisms for demyelination, acute flaccid paralysis, and ischaemic stroke were described, and potential mechanistic similarities from earlier coronavirus outbreaks were made with SARS-CoV-2. High rates of psychiatric comorbidity were noted in the SARS (1) pandemic and warning given over the emerging similarity in COVID-19.
Publication date / reference: 13/07/20. Tan et al. COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. J Thromb Thrombolysis.
Summary: The authors presented a PRISMA-compliant systematic search and review of acute ischaemic stroke in COVID-19 patients (n=54/4466 in observational cohorts; 1.2%). Stroke severity was often at least moderate with a high prevalence of large vessel occlusion.
Publication date / reference: 13/07/20. Christy. COVID-19: A Review for the Pediatric Neurologist. J Child Neurol.
Summary: This brief narrative review summarised some of the evidence for neurological complications of SARS-CoV-2 and other coronaviruses, including Guillain-Barre syndrome, multiple sclerosis, acute disseminated encephalomyelitis, anosmia, and febrile seizures. The author discussed these with reference to paediatric neurology; however, there is limited evidence of SARS-CoV-2 neurological sequelae in paediatric cases at present.
Publication date / reference: 23/06/20. Fiani et al. A Contemporary Review of Neurological Sequelae of COVID-19. Front Neurol.
Summary: This narrative review evaluated the putative mechanisms underlying the neurological manifestations of COVID-19. Fiani and colleagues provide a detailed explanation of SARS-CoV-2’s neurotropic potential, including pathways mediated by the ACE2 receptor, blood-brain-barrier disruption, cytokine storm and respiratory stress/hypoxia. They also review COVID-19 peripheral nervous system involvement and comment on the current state of treatment for these neurological sequelae.
Publication date / reference: 13/07/20. Aghagoli et al. Neurological Involvement in COVID-19 and Potential Mechanisms: A Review. Neurocrit Care.
Summary: This narrative review described in great detail the findings from salient reports of neurological abnormalities in COVID-19 and critically appraised the putative pathophysiological mechanisms underlying these manifestations.
Publication date / reference: 13/07/20. Nepal et al. Neurological manifestations of COVID-19: a systematic review. Crit Care.
Summary: This systematic review included a PRISMA analysis of 37 studies reporting neurological manifestations in COVID-19 (including case reports). Although reliable prevalence estimates of specific neurological findings cannot be concluded, the common neurological findings (headache, altered sensory perception) and more severe neurological complications, like encephalopathy, were concordant with other reviews.
Publication date / reference: 02/07/20 Ellul et al. Neurological Associations of COVID-19. Lancet Neurol.
Summary: This narrative review notes the high number of case reports of neurological complications after COVID-19. It theorises direct viral effects, immune-mediated disease, and neurological complications of systemic effects as possible mechanisms. The authors discuss aspects of encephalitis, encephalopathy, ADEM and myelitis, PNS and myopathic complications, cerebrovascular disease, and neuroinflammation. They call for better case definitions to distinguish non-specific complications from those caused by the virus, and predict that societal neuro-rehabilitative costs may be large.
Publication date / reference: 03/07/20 Nuzzo & Picone. Potential neurological effects of severe COVID-19 infection. Neurosci Res.
Summary: Narrative review discussing evidence supportive of the possibility that SARS-CoV-2 can cause a direct effect on the CNS, as well as an indirect CNS effect via lung injuries. Authors argue that given the potential early and long term neurocognitive effect of COVID-19, a possible treatment may be using antiviral therapies that can cross the BBB combined with neuroprotective drugs (such as those target inflammatory and oxidative stress), however no specific agents were suggested.
Publication date / reference: 07/07/20 Dong et al. Pathophysiology of SARS-CoV-2 infection in patients with intracerebral hemorrhage. Aging (Albany NY).
Summary: Narrative review of SARS-CoV-2 biology, ostensibly focused on patients with ICH, but much of the article is generic information about the virus. The authors put forward an argument that ICH patients may be more prone to viral infection, and also to the deleterious effects of virus-triggered cytokine storms, but primary data showing the clear directional causality implied by the authors are lacking.
Publication date / reference: 01/07/20. Cooper at al. COVID-19 and the Chemical Senses: Supporting Players Take Center Stage. Neuron.
Summary: This is an informative narrative review of mechanisms underlying changes in smell, taste, and chemical perception due to COVID-19, which also takes a balanced, critical look at the neuroinvasion hypothesis.
Publication date / reference: 02/07/20. Lahiri et al. Neuroinvasive Potential of a Primary Respiratory Pathogen SARS- CoV2: Summarizing the Evidences. Diabetes Metab Syndr.
Summary: Systematic search and narrative review of studies (n=58) advancing the hypothesis that phylogenetic similarities between SARS-CoV and SARS-CoV-2 may enhance neurotropism. It’s hard to appraise the search strategy and therefore the paper: specifically, the search was putatively keyword-based but reportedly yielded very small numbers of results given the known scope of this literature, implying possibly that it was unusually limited in some way, or that the full search results are not reported.
Publication date / reference: 06/20. Garg. Spectrum of Neurological Manifestations in Covid-19: A Review. Neurol India.
Summary: This is a narrative review of neurological manifestations, based on a reportedly “extensive” but unspecified search strategy. The authors discuss SARS-CoV2 broadly and include some helpful summary tables including 15 published cases of encephalitis/meningitis, a summary of three previous meta-analyses, and 22 GBS cases.
Publication date / reference: 18/06/20 Huang et al. Potential of SARS-CoV-2 to Cause CNS Infection: Biologic Fundamental and Clinical Experience. Front.Neurol
Summary: Review article arguing for the neuro-invasive potential of SARS-Cov-2. The authors summarise possible mechanisms for SARS-Cov-2 to induce CNS infection, drawing on previous biological evidence from other coronavirus infections.
Publication date / reference: 10/07/20 Gupta et al. Extrapulmonary manifestations of COVID-19. Nat Med
Summary: In this extensive and in-depth narrative review, the authors carefully examined the pathophysiology, presentation and management considerations for extrapulmonary manifestations of COVID-19, and outlined research priorities and therapeutic strategies for each of the organ systems examined. With specific reference to neurological manifestation of COVID, the authors provided a succinct summary of the range of neurological presentations reported to date, clinical management considerations and the putative pathological process involved. They also ask few pertinent questions for further research. It is worth a read in detail.
Publication date / reference: 08/07/20 Yavarpour-Bali and Ghasemi-Kasman. Update on Neurological Manifestations of COVID-19. Life Sci.
Summary: this narrative review describes the putative neuroinvasive mechanisms underlying the neurological manifestations of SARS-CoV-2.
Publication date / reference: 01/07/20. Beghi et al. COVID-19 infection and neurological complications: present findings and future predictions. Neuroepidemiology.
Summary: This brief narrative review highlights the neurological manifestations of COVID-19. Drawing parallels with other COVID and non-COVID viral infections, the authors propose the need for a surveillance system to monitor the frequency of immune-mediated neurological diseases, and for better collaboration between international organizations in order to detect, treat, and prevent future epidemics.
Publication date / reference: 27/06/20. Vallamkondu et al. SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets. Biochim Biophys Acta Mol Basis Dis.
Summary: A narrative review summarising aspects of CNS involvement but with a broader focus. SARS-CoV-2 structure and genetics are discussed alongside COVID-19 epidemiology, risk factors, time course and pathophysiology. Theories of its interaction with the CNS, dementia, and diabetes are highlighted. Diagnostic and therapeutic strategies are noted. Overall this is a broad primer which includes some neurological aspects but is not wholly focused on them.
Publication date / reference: 27/06/20. Katal et al. Neuroimaging findings in COVID-19 and other coronavirus infections: a systematic review in 116 patients. J Neuroradiol.
Summary: This is a systematic search extending to June 10th of Pubmed and Scopus, and an ad-hoc search of Google, for studies of neuroradiological findings of coronavirus infection. N=28 case reports or small case series were included, of which 20 focused on SARS-CoV-2 and reported on n=90 patients with neurological signs. 37/90 had no acute abnormalities on CT/MRI. Of the remainder, haemorrhage, PRES, thrombosis, acute necrotising encephalopathy, ADEM, leptomeningeal enhancement, and cortical FLAIR signal abnormalities were reported in scattered case reports. The authors call for research on potential long-term neurologic consequences of COVID-19.
Publication date / reference: 24/06/20. Azim et al. Neurological consequences of 2019-nCoV infection: a comprehensive literature review. Cureus.
Summary: The authors present a narrative review of neurological mechanisms and outcomes of SARS-CoV-2. An overview of mechanisms of CNS invasion (hematogenous, axonal) and damage (hypoxic, immune, cerebrovascular), and the relative frequency of CNS, PNS and skeletal muscle manifestations were summarised. The most common symptoms reported across studies included headache, dizziness, impaired consciousness, anosmia, dysgeusia, and myalgia. Additional neurological complications included encephalitis, myelitis, Guillain-Barre syndrome, and Miller Fisher syndrome. Greater severity of disease and pre-existing neurological conditions may increase the risk of neurological manifestations.
Publication date / reference: 16/06/20. Dos Santos et al. Neuromechanisms of SARS-CoV-2: a review. Front Neuroanat.
Summary: This narrative review summarises evidence for the neuroinvasive potential of SARS-Cov-2, discussing routes of access (e.g., olfactory, enteric) and potential mechanisms underlying its neurological manifestations. Potentially relevant pathways include those between the olfactory system and the amygdala, hippocampus, hypothalamus, brainstem, insular and frontal cortices. The authors highlight the need for more research on the involvement of the enteric nervous system and outline possible neuro-immune contributions. Several directions for research are presented including refinement of transgenic animal models, diffusion tensor imaging in COVID-19 patients, and artificial intelligence data mining.
Publication date / reference: 11/06/20. Koh et al. Epidemiological and clinical characteristics of cases during the early phase of COVID-19 pandemic: a systematic review and meta-analysis. Front Med.
Summary: This systematic review and meta-analysis reports on clinical and epidemiological features of Covid-19 cases during the early phase of the pandemic. Twenty-nine studies were identified (case report=18; case series=3; cross-sectional=8), reporting on 578 cases admitted between December 2019 and February 2020. Seven case reports had an unacceptable risk of bias rating. The pooled median age was 56 years in adult studies and 60% of cases were male. The most prevalent symptoms recorded on admission were fever, cough, and fatigue. Chest imaging revealed bilateral lung involvement in 90% of cases. The most common comorbid medical conditions were hypertension, diabetes, and cardiovascular disease.
Publication date / reference: 10/06/20. Bhatia and Srivastava. COVID-19 and stroke: incidental, triggered or causative? Ann Indian Acad Neurol.
Summary: This narrative review explores factors which potentially contribute to the occurrence of stroke in patients with COVID-19 infection. The search strategy was not described. The authors conclude that occurrence of stroke in the background of COVID-19 is likely multifactorial (speculatively involving underlying vascular risk factors, inflammatory/cytokine viral response and ACE pathway dysfunction).
Publication date / reference: 29/05/20. Aamodt et al. How does COVID-19 affect the brain? Tidsskr Nor Legeforen.
Summary: This brief narrative review outlines some key aspects of the CNS effects of COVID-19 including: the high frequency of neurological symptoms; the question of whether SARS-CoV-2 can directly infect brain cells; and the open question of whether it will be associated with longer-term neurological sequelae. The authors call for patients to be evaluated by a neurologist, and to receive rehabilitation and follow-up of residual symptoms.
Publication date / reference: 26/06/20. Mondal et al. Meningoencephalitis associated with COVID-19: A systematic review. Medrxiv.
Summary: This systematic review completed a comprehensive search (Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers) to 10/06/20 and summarised the findings from 29 cases of meningoencephalitis associated with COVID-19. Further, meta-analytic research is required to assess the prevalence of meningoencephalitis in patients with COVID-19.
Publication date / reference: 19/06/20 Garg et al. Encephalopathy in patients with COVID-19: A review. J Med Virol
Summary: This narrative review synthesises a systematic search (extending to 08/06/20) for case reports, case series, and cohort studies of COVID-19 associated encephalitis and encephalopathy. Qualitatively, most cohorts of severely ill patients to date report a high prevalence of encephalopathy. Myoclonus, various neuroimaging and EEG abnormalities, CNS invasion, cytokine storm, coagulopathy, hypoxia, and autoimmune demyelination are discussed. Selection bias remains a problem for generalisability.
Publication date / reference: 19/06/2020. Ghannam et al. Neurological involvement of coronavirus disease 2019: a systematic review. J Neurol.
Summary: Narrative review of a systematic search (extending to 14/05/20) of COVID-19 cases with neurological involvement on PubMed and Ovid Medline. 42 studies were included reporting on n=82 cases of neurological involvement. Among these cases 49% had cerebrovascular insults, 28% neuromuscular disorders (mainly GBS) and 23% encephalitides. Nearly all the evidence came from single case reports or very small case series, and alternative causes of neurological syndromes were not always excluded through careful workup.
Publication date / reference: 19/06/20 Kato et al. Neurological manifestations of COVID-19, SARS and MERS. Acta Neurol Belg.
Summary: Narrative review of the neurological effects of SARS-CoV (2002), MERS (2012) and SARS-CoV-2 (2019). The search was limited to March 2020 so the results focus more on past outbreaks, and mostly summarise case studies or small (n <5) series.
Publication date / reference: 17/06/2020 Alawieh et al. Letter: May Cooler Heads Prevail During a Pandemic: Stroke in COVID-19 Patients or COVID-19 in Stroke Patients? Neurosurgery
Summary: Authors suggest that evidence so far indicates that risk of stroke is no higher that background in young patients and those with mild disease.
Publication date / reference: 17/06/20 Baig et al. Heralding Healthcare Professionals: Recognition of Neurological Deficits in COVID-19. ACS Chem Neurosci.
Summary: This brief narrative review / position paper highlights some clinical observations and mechanistic hypotheses relevant to neurological manifestations of COVID-19, and calls for further research.
Publication date / reference: 16/06/20 Andrenelli et al. Systematic Rapid Living Review on Rehabilitation Needs Due to Covid-19: Update to May 31st 2020. Eur J Phys Rehabil Med.
Summary: This narrative synthesis of n=58 papers is an update of an existing living review of rehabilitation needs due to COVID-19. There were no RCTs or prospective controlled observational studies. Case series and other narrative reviews imply a high prevalence of nervous system involvement in COVID-19 patients that may require ongoing rehabilitation. Encephalopathy, delirium, fatigue, stroke, and GBS/variants feature prominently in the descriptive literature to date.
Publication date / reference: 15/06/2020 Blanco et al. Psychological Aspects of the COVID-19 Pandemic. Jour Gen Int Med.
Summary: Authors outline some potential adverse psychological consequences and offer suggestions for their prevention or mitigation.
Publication date / reference: 15/06/20 Asadi-Pooya et al. Central Nervous System Manifestations of COVID-19: A Systematic Review. J Neurol Sci.
Summary: The authors’ systematic search for descriptive studies of neurological manifestations in patients with COVID-19 finds only eight articles – possibly because the search extended no later than 26th March.
Publication date / reference: 11/06/20. Orsucci et al. Neurological features of COVID-19 and their treatment: a review. Drugs Context.
Summary: This narrative review searched solely PubMed (to 27/05/20) for articles on neurological features associated with COVID-19 (does not detail the search results). The authors stratified neurological features based on severity of COVID-19 illness, for example mild-illness being was more associated with headache, hypo/anosmia and myalgia whereas advanced illness was more associated with encephalopathy and delirium. Systematic meta-analysis evaluating the exact presence of these findings related to disease severity is required to substantiate these findings.
Publication date / reference: 11/06/20 Msigwa et al. The neurological insights of the emerging coronaviruses. J Clin Neurosci.
Summary: Narrative review presenting an overview of some neurological aspects of SARS-CoV (2002), MERS (2012) and SARS-CoV-2 (2019).
Publication date / reference: 11/06/20 Akhvlediani et al. What Did We Learn From the Previous Coronavirus Epidemics and What Can We Do Better: A Neuroinfectiological Point of View. Eur J Neurol
Summary: Correspondence reporting a systematic review of seven studies (all case reports or small case series) reporting nervous system involvement in patients with SARS-CoV1 and MERS-CoV infection. Noting significant reporting bias and a negligible involvement of neurologists in the previous epidemics, the authors conclude by calling for greater involvement of neurologists in the care of COVID-19 patients.
Publication date / reference: 11/06/20 Wang et al. Potential Mechanisms of Hemorrhagic Stroke in Elderly COVID-19 Patients. Aging.
Summary: Narrative review with a focus on discussing various mechanisms of haemorrhagic stroke in elderly patients with COVID-19. The propensity of the stroke risk factors hypertension and diabetes to associate with more severe viral illness is noted. The authors also discuss potential roles for inflammatory mediators, ACE2 expression, endothelial dysfunction, stress, and aging.
Publication date / reference: 11/06/20 Wang et al. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Neurol.
Summary: Systematic review of n=41 studies reporting neurological involvement in COVID-19. Among nonspecific neurological symptoms, fatigue, myalgia, headache, anorexia, and dizziness are prominent. Among studies with more than 50 patients, prominent specific neurological manifestations include olfactory and gustatory disorders, dysexecutive syndrome, agitation, and corticospinal tract signs. There are at least 11 case reports of Guillain–Barré syndrome and several other case reports of encephalitides.
Publication date / reference: 10/06/20 Bobker et al. COVID-19 and headache: a primer for trainees. Headache.
Summary: Informative and focused review which briefly summarises various hypotheses about why COVID-19 may cause headache (as estimated in around 13% of hospitalised patients). Putative disease-specific mechanisms include inflammatory cytokine release, stroke, cerebral venous thrombosis, and calcitonin gene related peptide. The authors call for prospective studies to capture the clinical characteristics and timing of headache in SARS-CoV2 infection.
Publication date / reference: 10/06/20 Cipriani et al. A complication of coronavirus disease 2019: delirium. Acta Neurologica Belgica.
Summary: Purportedly a review of COVID-19 associated delirium but is mainly generic delirium background and management.
Publication date / reference: 09/06/20 Purcell et al. Neurological Involvement of COVID-19 Patients: Making the Most of MRI. Radiology.
Summary: A letter calling for the integration of a post-contrast 3D FLAIR sequence to brain MRI protocols COVID-19 patients presenting with neurological symptoms. The authors argue that rates of leptomeningeal enhancement are underrepresented with current protocols.
Publication date / reference: 09/06/20 Dalakas. Guillain-Barré Syndrome: The First Documented COVID-19-triggered Autoimmune Neurologic Disease: More to Come With Myositis in the Offing. Neurol Neuroimmunol Neuroinflamm.
Summary: Review of GBS cases (n=11) in SARS-CoV-2 infection. The authors review emerging cases of autoimmune necrotizing myositis. As with numerous other GBS cases, ‘molecular mimicry’ is discussed as a potential reason as to why autoimmunity may occur at gangliosides.
Publication date / reference: 07/06/20 Koralnik & Tyler. COVID-19: a global threat to the nervous system. Ann Neurol.
Summary: Narrative review of the neurological manifestations of SARS-CoV-2. The authors cover the likely pathogenesis of para- and postinfectious sequelae and how these should be treated.
Publication date / reference: 05/06/20 Xiao et al. Survivors of COVID-19 are at high risk of posttraumatic stress disorder. Glob Health Res Policy.
Summary: Narrative review of PTSD and previous pandemics. The authors call for early intervention for the prevention of PTSD in COVID-19 survivors, relatives and frontline workers.
Publication date / reference: 05/06/20 Romoli et al. A Systematic Review of Neurological Manifestations of SARS-CoV-2 Infection: The Devil Is Hidden in the Details. Eur J Neurol.
Summary: A systematic review of 27 studies, the authors fail to establish manifestations of COVID-19 which are not immune mediated. They call for larger collaborations and more careful epidemiological studies.
Publication date / reference: 05/06/20 Defining causality in COVID-19 and neurological disorders. JNNP
Summary: In this Editorial, Investigators from the ongoing Coronerve study discuss considerations for making causal mechanistic attributions in neurological studies of Covid-19. Among other factors they emphasise the importance of weighing the strength, consistency, and specificity of associations, temporal and biological gradients, and the biological plausibility and coherence of data.
Publication date / reference: 04/06/20 Tsivgoulis et al. Ischemic Stroke Epidemiology During the COVID-19 Pandemic. Navigating Uncharted Waters with Changing Tides. Stroke.
Summary: Review of the retrospective cohort studies to date on stroke in patients with COVID-19.
Publication date / reference: 04/06/20 Finsterer et al. COVID-19 Polyradiculitis in 24 Patients Without SARS-CoV-2 in the Cerebro-Spinal Fluid. J Med Virol.
Summary: Literature review of 24 patients with GBS and SARS-CoV-2 infection. CSF was negative for the virus in all patients.
Publication date / reference: 03/06/20 Pryce-Roberts et al. Neurological complications of COVID-19: a preliminary review. J Neurol.
Summary: Review of our current knowledge of COVID-19’s impact in the CNS and PNS.
Publication date / reference: 03/06/20 Hassett et al. Acute Ischemic Stroke and COVID-19. Cleve Clin J Med.
Summary: Review of the current data on stroke and SARS-CoV-2 infection. The review tackles proposed pathological mechanisms such as vasculitis, coagulopathy and antiphospholipid antibodies.
Publication date / reference: 03/06/20 Jasti et al. A Review of Pathophysiology and Neuropsychiatric Manifestations of COVID-19. J Neurol.
Summary: Review of the current literature along with corresponding pathophysiologic mechanisms of nervous system involvement by the COVID-19.
Publication date / reference: 01/06/20 Niazkar et al. The Neurological Manifestations of COVID-19: A Review Article. Neurol Sci.
Summary: Review of the peripheral and central nervous manifestations of SARS-CoV-2 infection.
Publication date / reference: 01/06/20 Gavin et al. Mental Health and the COVID19 Pandemic. Ir J Psychol Med.
Summary: Authors describe the impact that the pandemic has had on mental health in Ireland and globally
Publication date / reference: 01/06/20 Hisham et al. COVID-19 – The Perfect Vector for a Mental Health Epidemic. BJPsych Bull.
Summary: Authors call for services to brace themselves for the ‘mental health tsunami’ that will unravel in the months and years to come due to the intrinsic and extrinsic impact of COVID-19 on the public.
Publication date / reference: 01/06/20. Winkler et al. A call for a global COVID-19 Neuro Research Coalition. The Lancet Neurology.
Summary: Authors propose closer global collaborations for the neurological research on SARS-CoV-2, particularly the inclusion of colleagues from low- or middle-income countries. They propose a network for interested clinicians, daily updates on publications and free to access case record forms.
Publication date / reference: 30/05/2020 Vindegaard et al. COVID-19 Pandemic and Mental Health Consequences: Systematic Review of the Current Evidence. Brain, Behavior, and Immunity.
Summary: Systematic review of psychiatric outcomes which included conclusions that COVID-19 patients displayed high levels of post-traumatic stress symptoms and increased levels of depression. Patients with pre-existing psychiatric disorders reported worsening of psychiatric symptoms.
Publication date / reference: 29/05/20 Pinzon et al. Neurologic Characteristics in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis. Front Neurol.
Summary: Meta-analysis of a systematic search (extending to 08/04/20) identifying n=33 studies (n=7559 patients) reporting on the frequency of neurologic complications of COVID-19. Only two included studies had a prospective cohort design. Nonspecific symptoms of myalgia/muscle injury and headache were most frequently reported. Cerebrovascular disease and encephalitides were estimated each to occur in around 4% of cases. Higher quality, prospective observational studies are needed to replicate these tentative observations.
Publication date / reference: 28/05/20 Mongan et al. COVID-19, Hypercoagulation and What It Could Mean for Patients With Psychotic Disorders. Brain Behav Immun.
Summary: The authors describe the evidence for coagulopathy in schizophrenia driven by environmental and putative biological mechanisms. Combined with the well-documented thromboembolic aetiology associated with SARS-CoV-2 they call for more research and careful risk stratification in high risk patient groups.
Publication date / reference: 28/05/20 Abboud et al. COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System. World Neurosurg.
Summary: Review of the neurological complications seen in SARS-CoV-2 infection. The authors also look to potential future complications of the infection in the CNS.
Publication date / reference: 28/05/20. Saleki et al. The Involvement of the Central Nervous System in Patients With COVID-19. Rev Neurosci.
Summary: authors discuss the contemporary evidence for neural involvement in SARS-CoV-2, whilst positing that the high pathogenicity of SARS-CoV-2 might be due to its neuroinvasive potential.
Publication date / reference: 27/05/2020 Luykx et al. Psychiatry in Times of the Coronavirus Disease 2019 (COVID-19) Pandemic: An Imperative for Psychiatrists to Act Now. JAMA Psychiatry.
Summary: Authors call for psychiatrists to stay alert.
Publication date / reference: 27/05/2020 Oertzen.COVID-19 – Neurologists Stay Aware!. Eur J Neurol.
Summary: Editorial asking neurologists to be mindful of neurological complications of COVID-19.
Publication date / reference: 26/05/2020 Gklinos et al. Neurological Manifestations of COVID-19: A Review of What We Know So Far. J Neurol.
Summary: Overview of what we know so far about neurological complications.
Publication date / reference: 26/05/2020 Zhou et al. Understanding the Neurotropic Characteristics of SARS-CoV-2: From Neurological Manifestations of COVID-19 to Potential Neurotropic Mechanisms. J Neurol.
Summary: Mechanistic review paper.
Publication date / reference: 26/05/2020 Kwon et al. Keep “time is brain,” even in the crisis of COVID-19. Neurological Sciences.
Summary: Authors suggests neurologists keep ‘time is brain’, by which they refer to acting quickly to spotting neurological complications of COVID-19.
Summary: Narrative review of the neurological complications of SARS-CoV-2, both common and rare. The authors compare experiences from previous pandemics to hypothesise what long-term neurological sequalae will follow infection.
Publication date / reference: 22/05/2020. Ahmed et al. Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review. Front Neurol
Summary: This discursive review is somewhat loose: the abstract states that “118 articles were thoroughly reviewed”, but only 59 are cited in the whole paper, and neither the search strategy nor its results are ever stated. There are also inaccuracies such as some of the references listed in Table 2 (“The spectrum of neurological manifestations of COVID-19”) were published in 2017 and actually report on MERS. There are some interesting case discussions.
Publication date / reference: 20/05/20 Gupta et al. Is COVID-19-related Guillain-Barré Syndrome Different? Brain Behav Immun.
Summary: The authors postulate that the pathogenesis of ‘COVID related GBS’ may be a different subtype. They describe the mechanism of ‘molecular mimicry’ seen in other GBS cases and the presence of antiganglioside antibodies.
Publication date / reference: 20/05/2020 Leonardi al. Neurological manifestations associated with COVID-19: a review and a call for action. Journal of Neurology.
Summary: Systematic review (29 studies) of the neurological manifestations of SARS-CoV-2.
Publication date / reference: 19/05/20 Tsai et al. The Neurologic Manifestations of Coronavirus Disease 2019 Pandemic: A Systemic Review. Front Neurol.
Summary: This meta-analysis of a systematic search (extending to 30/04/20) of neurological manifestations of COVID-19 identified n=79 studies, most of which contributed to a meta-analysis of symptom frequency. Olfactory/taste disorders, myalgia, and headache were again the most commonly reported symptoms. Of more florid neuropsychiatric outcomes, 9/227 patients (raw frequency 4.0%) experienced an acute cerebrovascular event and 22/585 (3.8%) experienced altered mental status. The authors report nearly double those estimates, but their weighting procedure doesn’t appear to weigh huge (n>200) studies commensurately more heavily than very small ones (n<20).
Publication date / reference: 19/05/20 Mei & Loeb. COVID-19: A Chronological Review of the Neurological Repercussions – What do We Know by May, 2020? MedRxiv Preprint.
Summary: The authors review 41 papers (n=630) of cases of SARS-CoV-2 with neurological manifestations. They also provide a concise report on the current guidelines for neurologists treating patients with COVID-19.
Publication date / reference: 19/05/2020 Ferrarese et al. An Italian Multicenter Retrospective-Prospective Observational Study on Neurological Manifestations of COVID-19 (NEUROCOVID). Neurological Sciences.
Summary: A new multicentre observational retrospective-prospective study proposed by leading neurologists in Italy. The study will gather data on disease course of SARS-CoV-2 and the short-medium term neurological impacts of the virus.
Publication date / reference: 18/05/2020. Ellul et al. Defining causality in COVID-19 and neurological disorders. SSRN preprint.
Summary: Authors discuss the complexity of establishing causality in COVID-19 associated neurological and neuropsychiatric disorders using Bradford Hill criteria.
Publication date / reference: 18/05/2020 Rogers et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry.
Summary: In depth systematic review and meta-analysis of the psychiatric complications of coronaviruses past and present (MERS, SARS-CoV & SARS-CoV-2). 72 studies (n=3559) Presentations in the study range from acute confusional states and delirium in severe ill patients, alongside a demonstration of post-viral psychiatric morbidity, namely PTSD and depression. Authors acknowledge the paucity of data in detailed neuropsychological assessments but do highlight that a third of survivors demonstrate a dysexecutive syndrome. Evidence is lacking however, to determine incidence, at risk groups, phenotypes and the relative contribution of the viral infection on such presentations(♦).
Publication date / reference: 16/05/2020
Summary: Non-systematic review for clinical neurologists to the parainfectious neurological manifestations of SARS-CoV-2. The authors also warn for vigilance to possible post-infectious neurological sequalae, such as seen in previous pandemics.
Publication date / reference: 16/05/2020 Bridwell et al. Neurologic complications of COVID-19. Am J Emergency Medicine
Summary: Call from emergency physicians to be vigilant to the neurological manifestations of SARS-CoV-2. They highlight pertinent literature on four main groups of sequelae: 1) cerebrovascular events, 2) encephalitis/encephalopathy, 3) GBS and 4) Haemophagocytic Lymphohistiocytosis (HLH). They also review the potential neuropsychiatric side effects of medications used in SARS-CoV-2, cautioning clinicians that antivirals like rotonavir can interact with anticoagulants to increase stroke risk and that many antimalarials carry a risk of psychological disturbance.
Publication date / reference: 16/05/2020 Whittaker et al. Neurological Manifestations of COVID-19: A review. Acta Neurol Scand.
Summary: Systematic review of 31 papers covering the neurological manifestations of SARS-CoV-2. Like previous reviews the authors cover various presentations gaining more credence as sequalae of infection like GBS. They also cover neuroinvasive mechanisms and suggest future directions of research.
Publication date / reference: 15/05/2020 Robert Belvis. Headaches During COVID‐19: My Clinical Case and Review of the Literature. Headache.
Summary: Self-case report from headaches in SARS-CoV-2 infection. The author believes headaches during the infection can be due to separate aetiologies. Interestingly, he believes a headache more than 7 days on from symptom onset could be attributed to the cytokine storm or even through hypoxia.
Publication date / reference: 15/05/2020 Bolay et al. COVID-19 is a Real Headache! Headache.
Summary: Authors decry the paucity of information concerning characteristics of headaches in the SARS-CoV-2 literature. They explore potential pathophysiological mechanisms of headache specific to SARS-CoV-2 and conclude it is a common non-respiratory symptom of COVID-19.
Publication date / reference: 15/05/2020 Montalvan et al. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery.
Summary: A systematic review (67 studies) on the neurological manifestation of SARS-CoV-2 amongst other coronaviruses. The authors describe potential pathogenesis of neurological insult, as well as the progression of the disease. They also give a summary of the evidence for candidate cellular targets in previous coronaviruses.
Publication date / reference: 13/05/20. Carrillo-Larco et al. Anosmia and dysgeusia in COVID-19: A systematic review. Wellcome Open Res.
Summary: A qualitative review synthesis, utilised a systematic search (to 20/04/20) for case series, cross-sectional, case-control and cohort studies of anosmia and dysgeusia associated with COVID-19. Based on 6 studies (total n=2757), the frequency of anosmia ranged from 22%-68%, whereas dysgeusia was present in 33% and ageusia in 20% of patients with COVID-19. Heterogeneity between studies made a systematic comparison difficult (especially with regard to differing definitions of taste disorders – this review calls for a standardised definition to be used). *this article is from May, hence the relative paucity of studies analysed
Publication date / reference: 11/05/2020 Asadi-Pooya et al. Seizures Associated With Coronavirus Infections. Seizure.
Summary: Review of literature on coronaviruses and seizure. The authors suggest patients with SARS-CoV-2 could develop seizures through hypoxia, metabolic derangements, organ failure, or cerebral damage.
Publication date / reference: 07/05/2020 Ellul et al. Neurological Associations of COVID-19. Lancet Neuro.
Summary: Widely scoped systematic review which summarises reported neurological manifestations of COVID-19 in the context of neurological manifestations of other human coronaviruses and other respiratory viruses (♦).
Publication date / reference: 05/05/2020 Kwong et al. COVID-19, SARS and MERS: A Neurological Perspective. Journal of Clinical Neurosciences.
Summary: Non-systematic review summarising the impact of SARS-CoV-2 on the nervous system. Drawing on evidence from previous pandemics the authors explore mechanism of neurotropism and its manifestations.
Publication date / reference: 05/05/2020 Zhu et al. Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis. Fam Med Community Health.
Summary: Meta-analysis of Chinese data on clinical features of COVID-19; headache was seen in 11.3% of pooled total.
Publication date / reference: 28/04/2020. Herman C, et al. Scoping review of prevalence of neurologic comorbidities in patients hospitalized for COVID-19. Neurology.
Summary: Systematic review and meta-analysis which explores published data on neurological comorbidities and sequalae of COVID-19 patients.
Publication date / reference: 11/04/2020 Asadi-Pooya et al. Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci.
Summary: Small systematic review of neurological manifestations of COVID-19 infections.
Editorials and position statements
Publication date / reference: 15/10/2020. Costa & Silva-Pinto. Neurological Manifestations and COVID-19. Acta Med Port.
Publication date / reference: 13/11/2020. Amy M. Lavery et al. Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission – United States, March-August 2020. MMWR Morb Mortal Wkly Rep.
Publication date / reference: 11/11/2020 Antonietta Gigante et al. In systemic sclerosis patients the anxiety disorder and Raynaud’s phenomenon are increased during lock down period for COVID-19 pandemic. Intern Emerg Med.
Publication date / reference: 10/11/2020. Edlow et al. Delayed reemergence of consciousness in survivors of severe COVID-19. Neurocrit Care.
Publication date / reference: 04/11/2020 Palomar-Ciria et al. Commentary to “Schizophrenia and COVID-19 Delirium”, an update. Psychiatry Res.
Publication date / reference: 01/11/20 Sun & Guan. Letter to the Editor: Is Coronavirus Disease 2019 A Real Threat to the Nervous System? World Neurol.
Publication date / reference: 02/11/20. Latorre & Rothwell. Myoclonus and COVID-19: A Challenge for the Present, a Lesson for the Future. Mov Disord Clin Pract.
Publication date / reference: 04/11/20. Finsterer et al. Is Guillain Barre syndrome truly caused by SARS-CoV-2? Am J Emerg Med.
Publication date / reference: 29/10/2020 López-Díaz et al. COVID-19 Infection During Pregnancy and Risk of Neurodevelopmental Disorders in Offspring: Time for Collaborative Research. Biol Psych.
Publication date / reference: 09-10/20 Garg et al. Silent hypoxemia in COVID-19: dangerous, if gone undetected. Neurol India.
Publication date / reference: Nov/Dec 2020. Ruiz de Pellon Santamaria. Psychosis Treatment During COVID-19 Pandemic and the Potential Role of Phenothiazines: A Call for Research Studies. J Clin Psychopharmacol.
Publication date/reference: 4/11/20. Kuan-Po Peng et al. Association between COVID-19 and headache: What evidence and history tell us. Cephalalgia.
Publication date / reference: 21/10/20 Brundin et al. Is COVID-19 a Perfect Storm for Parkinson’s Disease? Trends Neurosci.
Publication date/reference: 06/10/20 Keng et al. Effectively Caring for Individuals With Behavioral and Psychological Symptoms of Dementia During the COVID-19 Pandemic. Front Psychiatry.
Publication date/reference: 06/11/2020 Santos de Lima et al. Epileptiform activity and seizures in patients with COVID-19. J Neurol Neurosurg Psychiatry.
Publication date/reference: 07/11/2020. Mohkhedkar et al. Possible auto-antigens that may explain the post-infection autoimmune manifestations in COVID-19 patients displaying neurological conditions. J Infect Dis.
Publication date/reference: 07/11/2020 Fan et al. Delayed catastrophic thrombotic events in young and asymptomatic post COVID-19 patients. J Thromb Thrombolysis.
Publication date / reference: 12/10/20. Araya-Quintanilla et al. Relation between COVID-19 and Guillain-Barre syndrome in adults. Systematic review. Neurologia.
Publication date / reference: 8/10/20. Lorenzo et al. Ischaemic stroke associated with COVID-19 in dialysis patients. Nefrología.
Publication Date / Reference: 09/10/2020 Ma et al. Stroke and Thromboprophylaxis in the Era of COVID-19. J Stroke Cerebrovasc Dis.
Publication Date / Reference: 01/11/2020 Hert et al. Prioritizing COVID-19 vaccination for people with severe mental illness. World Psychiatry.
Publication Date/Reference: 26/10/2020 Laxe et al. Neurorehabilitation in the times of Covid-19: insights from the Spanish Neurorehabilitation Society (SENR). Brain Inj.
Publication Date/Reference: 29/10/2020 Shor et al. MR Imaging of the Olfactory Bulbs in Patients with COVID-19 and Anosmia: How to Avoid Misinterpretation. AJNR.
Publication Date/Reference: 11/20. Agarwal et al. Letter by Agarwal et al Regarding Article, “Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era”. Stroke.
Publication Date/Reference: 11/20. Diegoli et al. Response by Diegoli et al to Letter Regarding Article, “Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era”. Stroke.
Publication Date/Reference: 11/2020. Ishida et al. Response by Ishida et al Regarding Article, “SARS-CoV-2 and Stroke in a New York Healthcare System”. Stroke.
Publication date/reference: 26/10/2020. Rajkumar Rajendram et al. Letter by Rajendram et al Regarding Article, “Clinical Characteristics and Outcomes of COVID-19 Patients With a History of Stroke in Wuhan, China”. Stroke.
Publication date/reference: 26/10/2020. Timotius Ivan Hariyanto et al. Dementia is a predictor for mortality outcome from coronavirus disease 2019 (COVID-19) infection. Eur Arch Psychiatry Clin Neurosci.
Publication date/reference: 26/10/2020. Joseph Kwan et al. Letter by Kwan et al Regarding Article, “Acute Stroke Management During the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?”. Stroke.
Publication date/reference: 26/10/2020. Sajaeev et al. Letter by Sajeev et al Regarding Article, “SARS-CoV-2 and Stroke in a New York Healthcare System”. Stroke.
Publication date/reference: 21/10/2020. Indu Kapoor et al. COVID-19 and Diagnosing Brain Death: An Ambiguity. Turk J Anaesthesiol Reanim.
Publication date/reference: 11/2020. Frank Brodhead. Mental Health Effects of COVID-19. Am J Nurs. 2020.
Publication date/reference: 29/10/2020. Edouard Januel et al. Ischaemic strokes associated with COVID-19: is there a specific pattern?. J Neurol Neurosurg Psychiatry.
Publication date/reference: 1/10/2020. Mehmet Nuri Yakar et al. Re: COVID-19 and Diagnosing Brain Death: An Ambiguity. Turk J Anaesthesiol Reanim.
Publication date/reference: 30/09/2020. Aline C Olivieria et al. Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?. Front Neurosci.
Publication date / reference: 11/2020 Solomon et al. Provisional case definitions for COVID-19-associated neurological disease – Authors’ reply. Lancet Neurol.
Publication date / reference: 23/10/2020 Selioutski et al. Letter to the Editor: Electroencephalography at the time of COVID-19 pandemic in Italy. Neurol Sci.
Publication date / reference: 21/10/20 Rahman et al. Pathogenesis and management of cerebral venous sinus thrombosis (CVST); a devastating complication of SARS-CoV2. Br J Neurosurg.
Publication Date/Reference: 22/09/20. Chen et al. Maintenance of Stroke Care Quality amid the Coronavirus Disease 2019 Outbreak in Taiwan. J Stroke.
Publication Date/Reference: 15/10/20. Burlacu et al. Is Thrombophilic Genetic Profile Responsible for an Acute Ischemic Stroke in a COVID-19 Male Patient? Clin Appl Thromb Hemost.
Publication Date/Reference: 14/10/20. Pilotto et al. COVID-19 impact on consecutive neurological patients admitted to the emergency department. J Neurol Neurosurg Psychiatry
Publication Date/Reference: 15/20/20. Modin et al. Acute COVID-19 and the Incidence of Ischemic Stroke and Acute Myocardial Infarction. Circulation.
Publication date/ reference: 09/20 Karimi & Sedaghat. Letter to the editor. Concerning the article entitled ”Guillain Barre syndrome associated with COVID-19 infection: A case report”. J Clin Neurosci.
Publication date/ reference: 09/10/2020 Valença et al. COVID-19, neurocognitive disorders, and civil capacity. Braz J Psychiatry
Publication date/ reference: 13/10/20. Itzhaki. Antivirals Against SARS-CoV2: Relevance to the Treatment of Alzheimer’s Disease. J Alzheimers Dis.
Publication date / reference: 07/11/20 Oldham et al. Characterising neuropsychiatric disorders in patients with COVID-19. Lancet Psychiatry.
Publication date / reference: 07/11/20 Wade et al. Characterising neuropsychiatric disorders in patients with COVID-19. Lancet Psychiatry.
Publication date / reference: 13/10/20 Wijeratne et al. Post-COVID 19 Neurological Syndrome (PCNS); a novel syndrome with challenges for the global neurology community. J Neurol Sci.
Publication date / reference 09/20. Mowla. Stoke Care During the COVID-19 Pandemic; a Global Challenge. Iran J Med Sci.
Publication date / reference: 11/20. Li et al. Provisional case definitions for COVID-19-associated neurological disease. Lancet Neurol.
Publication date / reference: 15/10/20. Oertzen et al. EAN consensus statement for management of patients with neurological disease during the COVID-19 pandemic. Eur J Neurol.
Publication date / reference: 28/08/20. Kermanshahi et al. Can Infection of COVID-19 Virus Exacerbate Alzheimer’s Symptoms? Hypothetic Possible Role of Angiotensin-Converting Enzyme-2/Mas/ Brain-Derived Neurotrophic Factor Axis and Tau Hyper-phosphorylation. Adv Biomed Res.
Publication date / reference: 20/10/20. Lad et al. Neurological Manifestations in Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). Indian J. Pediatr.
Publication date / reference: 13/10/20 (pre-print). Borisova et al. Air pollution particulate matter as a potential carrier of SARS-CoV-2 to the nervous system and/or neurological symptom enhancer: arguments in favor. Environ Sci Pollut Res Int.
Publication date/ reference: 13/10/20 Butler et al. Neuropsychiatric complications of covid-19. BMJ.
Publication date/ reference: 05/10/20 Frank. Catch me if you can: SARS-CoV-2 detection in brains of deceased patients with COVID-19. Lancet Neurol.
Publication date / reference: 10/20. Lucchese. Cerebrospinal fluid findings in COVID-19 indicate autoimmunity. Lancet Microbe
Summary: The author cites previous studies showing reporting negative CSF finding of SARS-Cov-2 in COVID-19 patients, and one reporting high levels of autoantibodies found in COVID-19 patients. From which the letter argues that neurological manifestations of COVID-19 are not caused by direct cytopathic effects but indirect immune-mediated mechanisms targeting various unknown elements of the nervous system.
Publication date/ reference: 09/07/20. Motaghinejad & Gholami. Possible Neurological and Mental Outcomes of COVID-19 Infection: A Hypothetical Role of ACE-2\Mas\BDNF Signaling Pathway. Int J Prev Med.
Publication date / reference: 10/2020. McClain 4th et al. Letter to the Editor Regarding “Incidence of Acute Ischemic Stroke and Rate of Mechanical Thrombectomy During the COVID-19 Pandemic in a Large Tertiary Care Telemedicine Network”. World Neurosurg.
Publication date / reference: 09/10/2020 Newcombe et al. Neuroanatomical substrates of generalized brain dysfunction in COVID-19. Int Care Med.
Publication date / reference: 08/10/2020. Baig. Covert Pathways to the Cranial Cavity: Could These Be Potential Routes of SARS-CoV-2 to the Brain?. ACS Chem Neurosci.
Publication date/reference: 28/09/2020 Finsterer et al. SARS-CoV-2-associated critical ill myopathy or pure toxic myopathy? Int J Infect Dis.
Publication date / reference: 27/09/2020 Diaz et al. The role of neurotropism in psychiatric patients with COVID-19 Eur Arch Psychiatry Clin Neurosci. Eur Arch Psychiatry Clin Neurosci
Summary: Short narrative review which repeats the oft-repeated but thus far poorly evidenced hypothesis that the neurotropism of SARS-CoV-2 is directly responsible for neuropsychiatric morbidity (in this case psychiatric disorders such as mania).
Summary: Editorial. “Recent publications provide evidence of retinal microangiopathy in patients with confirmed COVID-19 infection. Emphasis should be given to better reporting of clinically significant ocular symptoms, e.g. new scotoma, which could indicate the need for a retinal examination as well as follow-up testing after recovery from COVID-19.”
Publication date / reference: 12/09/20. Ansari & Riyaz. Letter to the Editor: Transneural transmission in COVID-19 without a positive nasopharyngeal swab. Surg Neurol Int.
Publication date / reference: 28/08/20. Sanclemente-Alaman et al. Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2. Front Immunol.
Summary: A thorough and wide-ranging assessment of the extant animal and cellular models being used to study the impact of SARS-CoV-2 on the nervous system. They have also provided a specific focus on neural cell lines and brain organioids.
Publication date / reference: Aug 2020. Perez. Looking ahead: The risk of neurologic complications due to COVID-19. Neurol Clin Pract.
Publication date / reference: 18/7/2020 Bara et al. Can neuromodulation support the fight against the COVID19 pandemic? Transcutaneous non-invasive vagal nerve stimulation as a potential targeted treatment of fulminant acute respiratory distress syndrome
Summary: Short opinion piece exploring the potential use of Vagus Nerve Stimulation in COVID-19 patients with acute respiratory distress syndrome. Rationale being efferent vagus nerve fibres can exert an inhibitory effect on cytokine release and hence reduce inflammation.
Publication date / reference: 03/10/20. Costa et al. Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19? Eur J Pharmacol.
Publication Date/Reference: 09/2020. Cynthia M.A Geppert. The Brain in COVID-19: No One Is Okay. Fed Pract.
Publication Date/Reference: 8/10/2020. Dhillon et al. Hemorrhagic Neurologic Manifestations in COVID-19: An Isolated or Multifactorial Cause?. AJNR Am J Neuroradiol.
Publication date / reference: 25/08/20. Pincherle et al. Intensive Care Admission and Early Neuro-Rehabilitation. Lessons for COVID-19? Front Neurol.
Summary: Using their experience in providing acute interdisciplinary neuro-rehabilitation for managing severely brain-injured patients, the authors recommend early and intensive rehabilitation for severe COVID-19. This review covers several areas of potential requiring rehabilitation in recovering patients based on non-systematic, but scoping review of the literature. These include deficits in cognition, multimodal sensory perception, as well as importantly, cardiovascular and respiratory retraining.
Publication date / reference: 09/10/20. Ferrai & Quaresima et al. Hypoxemia in COVID-19: cerebral oximetry should be explored as a warning indicator for mechanically ventilated adults with COVID-19. Respir Res.
Publication date / reference: 2020. Ramphul et al. Headache may not be linked with severity of coronavirus disease 2019 (COVID-19). World J Emerg Med.
Summary: In this correspondence, Ramphul and colleagues reported the results of a meta-analysis of studies assessing the association of headache with severity of COVID-19. From a yield of seven studies the odds ratio was calculated at 1.32 (95% CI 0.98-1.80). It was concluded that headache was not a reliable prognostic factor for severe COVID-19.
Publication date / reference: 25/09/20. Finsterer & Scorza. SARS-CoV-2 myopathy. J Med Virol.
Publication date / reference: 25/09/20. Lo et al. Covid-19, fatigue and dysautonomia. J Med Virol.
Publication date / reference: 22/09/20. Foresti et al. COVID-19 provoking Guillain-Barrè Syndrome: the Bergamo case series. Eur J Neurol.
Publication date / reference: 22/09/20. Josephson & Kamel. Neurology and COVID-19. JAMA.
Publication date / reference: 16/09/20. Shahani et al. Universal SARS-CoV-2 testing versus symptom based screening and testing in an inpatient psychiatric setting. Psychiatry Res.
Publication date / reference: 16/09/20. Anand et al. Comment on COVID-19 in patients with myasthenia gravis: Author response. Muscle Nerve.
Publication date / reference: 08/09/20. Harikrishnan. Etiogenic Mechanisms for Dygeusia in SARS-CoV-2 Infection. J Craniofac Surg.
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Publication date / reference: 12/08/20. Geyer et al. Movement Disorders in COVID-19: Whither Art Thou? Tremor Other Hyperkinet Mov (N Y).
Summary: In this interesting correspondence, the authors described the lack of reported cases of movement disorders in patients with COVID-19. According to their expert knowledge, only four reports existed at the time of publication, including myoclonus, hypokinetic-rigid syndrome and tremor/ataxia. The authors speculated over potential reasons for the paucity of these findings, especially considering the relevative commonality of movement disorders in patients with