5th March - the COVID-19 coronavirus compendium

First dose of vaccines, re-infection, and genomics

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In the past few weeks, we learnt that a single dose of the Oxford / AstraZeneca and BioNTech / Pfizer vaccines offer some protection after a single dose, that re-infection is rare, and that a genetic variant inherited from Neanderthals provides some protection from severe disease.

Vaccines

Protection from the ChAdOx1 nCoV-19 vaccine from Oxford University and AstraZeneca did not wane up to 3 months after vaccination with a single dose, and had a higher efficacy in those who had a longer interval between the first and second doses, supporting the UK approach to delay second doses.

A study of more than 500,000 recipients of the BioNTech / Pfizer vaccine in Israel found that the vaccine had 46% efficacy after one dose and 92% after two doses. Protection from death was 72% after one dose.

Healthcare workers previously infected with COVID-19 had stronger immune responses against a single dose of an mRNA vaccine than those who had not been previously infected, suggesting that such people may not need a second dose.

Social distancing

Countries that reduced mobility, based on data from Apple and Google, saw less transmission of COVID-19, although transmission and mobility were uncoupled in some countries at some times.

Transmission

A large study of more than 3.2 million US patients found that 0.3% tested positive more than 90 days after a first infection, compared to 3% testing positive who had not previously been infected, showing that re-infection is rare.

More symptoms and a higher viral load were associated with an increased risk of transmission in US Air Force trainees living together.

Treatments

IL-6 inhibitors were found to improve survival in the REMAP-CAP trial, although two other studies found that tocilizumab and sarilumab were not effective. Statin use was associated with lower COVID-19 mortality in a retrospective study.

Suramin, a 100-year old drug, binds to the SARS-CoV-2 RNA-dependent RNA polymerase and acts by blocking the binding of RNA to the enzyme, although the drug has not yet been tested in animals or humans. 311 potential new treatments against COVID-19 were identified using a biological activity-based modelling screen.

Treatment of infected Syrian hamsters with neutralising antibodies reduced viral levels in the lungs, but not in nasal turbinates, leaving the animals still infectious.

The RECOVERY trial confirmed their earlier finding that dexamethasone treatment reduces mortality in those who received respiratory support. This cheap drug is now widely used and has saved thousands of lives.

Immunology

T cell responses were detected in all 100 COVID-19 patients 6 months after infection, with stronger responses in those who had a symptomatic infection. Most potent antibodies against SARS-CoV-2 target the tip of the spike receptor binding domain.

Variants

The B.1.1.7 variant, first identified in the UK, is susceptible to neutralising antibodies from previous variants, showing that it is unlikely to affect the risk of re-infection. However, this strain was estimated to have a 43-90% higher reproduction number than previous variants. The D614G mutation found in this variant was shown to enhance binding to ACE-2, increase replication in epithelial cell cultures, and increase transmission in both mice and ferrets, giving it a competitive advantage in humans.

Several studies examined the effect of the 501Y.V2 variant, first identified in South Africa. Convalescent sera from recipients of the BNT162b2 mRNA vaccine from BioNTech / Pfizer showed reduced neutralising activity against viruses containing the E484K mutation, seen in this variant. A second study found that E484K, K417N and N501Y mutations cause widespread escape from monoclonal antibodies. Similarly, pseudovirus containing the spike protein of SARS-CoV-2 501Y.V2 completely escaped neutralisation by therapeutic antibodies, although this strain did not show higher infectivity.

Diagnostics

An automated platform for the detection of tens of thousands of SARS-CoV-2 samples in a single run was developed.

The prevalence of COVID-19 antibodies in Chinese blood donors was found to be between 0.0028% and 2.66%, with the highest rates in Wuhan.

Receptors

Levels of coronavirus receptors, ACE2, TMPRSS2, and CTSL, varied with age, sex, and smoking status, suggesting that expression may affect pathogenesis.

Many bat species cannot be infected with SARS-CoV-2 or SARS-CoV, due to variation in their ACE-2 receptors.

Risk of severe disease

Several non-communicable diseases, including obesity, hypertension, respiratory disease, and psychiatric disease, were associated with an increased risk of death from COVID-19, using data from more than 500,000 people from UK Biobank.

Severe asthma and COPD were found to increase mortality from COVID-19, and use of inhaled corticosteroids improved survival rates for those with asthma, but not COPD.

Genomics

An isoform of OAS1 inherited from Neanderthals was found to reduce COVID-19 severity in people of European ancestry.

Ben Johnson

Magazine Editor, Nature Medicine, Springer Nature

I trained as a virologist, starting with an undergraduate degree in virology from the University of Warwick, UK. My PhD, in influenza virus genetics and immunoevasion, was from Public Health England and the University of Reading, UK, with Maria Zambon and Wendy Barclay. My research interests then moved to smallpox vaccines, viral ion channels and cell adhesion, while a postdoc at Imperial College London with Geoffrey Smith, FRS. I then joined open-access publisher BioMed Central in 2011 as an editor and then associate publisher and was Head of Communities & Engagement at Springer Nature from 2016, running the Nature Research Communities and other online engagement activities for researchers. I joined Nature Medicine in 2021, with responsibility for news and opinion content, and am based in the London office.