Alex Nowbar’s journal review—18 September 2020

Alex Nowbar reviews the latest research from the top medical journals

Genetic susceptibility to covid-19?

To get into human cells, the SARS-CoV-2 viral spike protein binds to the human ACE2 receptor. This process depends on a human enzyme called TMPRSS2. TMPRSS2 is differentially expressed in different ethnic groups (which is thought to contribute to higher prostate cancer rates in black men compared with white men) so could be responsible for the racial variation in covid-19 infection and death rates. How reliable is this information? We don’t yet know. All Bunyavanich et al did was look at nasal epithelium collected from over 300 people with asthma in 2015 to 2018 for research about asthma biomarkers and report the difference in nasal gene expression of the enzyme. They found that TMPRSS2 expression was higher in black people compared with Asian, Latina, mixed race, and white people. This observation is interesting, but it doesn’t directly tell us anything about covid-19 susceptibility.

JAMA doi:10.1001/jama.2020.17386

The Russian vaccine

Logunov et al present data from 76 volunteers who received a recombinant adenovirus vaccine containing the gene for the viral spike protein. The vaccine had two adenovirus components. Two different formulations of this vaccine were tested. The treatment regimen was the first vaccine component followed by the second component three weeks later. This wasn’t a randomised trial, but in this small number (of primarily healthy young men) there were no serious adverse events and there was appropriate immune response seen afterwards. There were mild adverse events (such as pain at the injection site, hyperthermia, and headache), but, without a placebo-control, it is not possible to know how much of this is attributable to the vaccine. These data are promising, but the next stage is to demonstrate actual protection against the virus.

Lancet doi:10.1016/S0140-6736(20)31866-3

Exploring confidence in vaccines worldwide

That not everyone sees vaccines for the saving grace they have been for many diseases is unfathomable to me. This modelling study estimated confidence in the importance, safety, and effectiveness of vaccines using surveys from 2015 to 2019 across 149 countries. This is topical, given the vaccines that are being developed to tackle the covid-19 pandemic. The good news for Europe is that vaccine confidence has increased over time, although recently there was a loss in confidence in Poland, where there was a highly organised anti-vaccine movement. The Philippines and Indonesia experienced a dramatic decrease in vaccine confidence, and one of the lowest ranked countries in vaccine confidence was Japan. I highly recommend reading the discussion of this paper as it so elegantly describes the story behind many such observations.

Lancet doi:10.1016/S0140-6736(20)31558-0

G-CSF for covid-19?

Covid-19 is associated with lymphopenia. The hypothesis that recombinant granulocyte colony-stimulating factor (G-CSF) might benefit people with severe covid-19 because it increases the lymphocyte count isn’t unreasonable. The next step was a randomised controlled trial. This was not a blinded trial unfortunately, justified in the paper as: “A placebo-controlled trial was not performed because of the outbreak emergency.” So, because it’s an emergency, it’s not important to find out if treatments really work? Anyway, the study found no benefit for time to clinical improvement (the primary endpoint).While it remains possible that the trial was too small (and the patients not comorbid enough due to the exclusion criteria) to detect a benefit of G-CSF, it seems unlikely. One of the good things about the trial design though was use of a seven-category ordinal scale for the primary outcome. This helps to get information from the participants, because an outcome such as death requires many more patients to demonstrate a difference. The downside, however, is that the outcome assessment should really be done blinded.

JAMA Intern Med doi:10.1001/jamainternmed.2020.5503

Removing tracheostomies

Tracheostomies are traditionally decannulated after a trial of capping. It gets the job done, but it’s a conservative approach. Does it mean decannulation happens as soon as possible after weaning from mechanical ventilation? The idea is that the sooner the better for reducing complications. This large, multicentre, Spanish trial provides evidence for a more effective method. Patients who had been weaned from mechanical ventilation were randomised to one of two decannulation strategies: decannulation timing based on the required frequency of suction plus continuous high flow oxygen, or standard care (decannulation after a 24 hour trial of capping the tracheostomy tube with intermittent high flow oxygen). The suction-based strategy reduced the time to decannulation (the primary endpoint) while also reducing adverse events such as pneumonia and reducing the length of stay in hospital. One major limitation of this trial is the potential for bias after randomisation because staff were aware of which group the patients were in. Practically it would have been impossible to blind staff to the interventions, but some attempt could have been made at blinding the staff who were assessing and recording outcomes. Nevertheless, this is strong evidence in support of a suction-frequency strategy for decannulation.

N Engl J Med doi:10.1056/NEJMoa2010834

Alex Nowbar is a clinical research fellow at Imperial College London