12th February - the COVID-19 coronavirus compendium

New variants, viral load, and community transmission

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In the past two weeks, researchers found that the mRNA vaccines from Moderna and BioNTech / Pfizer appear to protect against new variants, a high viral load increases transmission, and the outbreak in the US is almost exclusively amongst people aged 20-49.

Vaccines

Vaccine hesitancy in the UK and USA are sufficiently high to prevent herd immunity being reached, according to a randomised controlled trial of online misinformation. Recent exposure to misinformation caused a decline of 6-7 percentage points amongst those who said they would definitely accept a vaccine, and sociodemographic groups were differentially impacted. In France, almost 30% showed vaccine hesitancy, with rates highest amongst women, the young and the old, and those with lower educational levels.

The Sputnik V vaccine, a heterologous prime-boost with two different adenovirus vectors, was shown to be 92% effective in a phase 3 clinical trial of almost 20,000 people. The immunogenicity of the BNT162b2 vaccine, made by Pfizer / BioNTech and licensed in humans, was characterised in rhesus macaques, as well as a similar vaccine comprising the receptor-binding domain, termed BNT162b, which is in phase 1 trials.

The CoronaVac inactivated vaccine was shown to be safe and immunogenic in a phase 1 / 2 clinical trial. A single-dose mRNA vaccine based on the spike receptor binding domain was developed and shown to protect mice from challenge more than 6 months after vaccination, as was a vaccine based on Modified Vaccinia Ankara, a poxvirus.

Treatments

Combination therapy with two monoclonal antibodies, bamlanivimab and etesevimab, reduced viral load in mild to moderate COVID-19 patients. Peg-interferon lambda was shown to be effective at accelerating viral decline in COVID-19 out-patients in a phase 2 clinical trial of 60 patients. A monoclonal antibody, MD65, isolated from a COVID-19 patient protected mice from a lethal infection. Azithromycin did not improve survival of COVID-19 patients, in the RECOVERY trial in the UK.

A mouse model with human-like lungs was found to support growth of several coronaviruses, including SARS-CoV-2 and some bat coronaviruses. The model was used to show anti-viral activity for EIDD-2801, a broad anti-viral in clinical trials. A Cas13a-based treatment for influenza A virus and SARS-CoV-2 was developed and shown to degrade viral RNA in a hamster model of infection.

The structure of the RNA genome of SARS-CoV-2 allowed identification of several FDA-approved drugs that are predicted to bind, and may be candidates for treatment. Dexamethasone treatment was estimated to have saved 12,000 lives in the UK between July and December 2020.

Methylprednisolone combined with intravenous immunoglobulins improved the outcome for children with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2.

Social distancing

People aged 20-49 are the only age group that are sustaining community transmission in the US, according to a study of mobility data from October 2020.

Contact surveys in the US found that there was a large drop in daily contacts in the early outbreak, but that contact increased later in the pandemic, with contact highest amongst people under 45 years and males.

Transmission

A high viral load increases the risk of transmission, according to a study of more than 300 COVID-19 patients in Catalonia, Spain. Connectivity is likely the main driver of variance in COVID-19 outbreaks in sub-Saharan African, with little role for climate, according to a model.

An analysis of more than 5 million people in Catalonia, Spain, found that people of older age, men, and those with co-morbidities had worse outcomes from COVID-19. Migrant workers in Singapore had low death rates from COVID-19, with many having no symptoms at all. Almost half of the population of Karnataka, India, tested positive for COVID-19 in a large serological study.

Variants

Variants arise in the coronavirus genome because the same deletions re-occur in recurrent deletion regions, which map to defined antibody epitopes. This is despite corrections being made by the virus’ proof-reading enzyme.

16 lineages of the virus were identified in a major sequencing study from South Africa, including a variant with the D614G mutation, which is now widespread.

An immunosuppressed individual chronically infected with SARS-CoV-2 generated mutations in the virus after receiving convalescent plasma therapy. Mutations included D796H and a deletion in the N-terminal domain of the spike, which reduced sensitivity to the plasma therapy. Viral variants may be more likely to arise in such chronically-infected people.

Several studies looked at the ability of antibodies generated by vaccines to neutralise new variants of the virus. Antibodies generated by the Moderna / mRNA-1273 and Pfizer-BioNTech / BNT162b2 vaccines were shown to effectively neutralise variants of the virus, but with a small reduction in activity against variants with the E484K or N501Y mutations. The D614G mutation was found to improve entry of a pseudovirus via improved binding to the ACE-2 receptor.

A study from BioNTech researchers confirmed that vaccine-induced sera continued to neutralise the UK variant, albeit at slightly reduced levels. Another study found that antibodies generated by the BioNTech vaccine continued to neutralise the E484K, N501Y, and D614G variants, despite some small reductions in activity.

Healthcare

Provision of anti-retroviral therapy (ART) for people with HIV in South Africa was well maintained during the pandemic, but HIV testing and initiation of ART was heavily reduced. People with HIV were slightly more likely to have severe COVID-19 disease and death, in a study from the US.

Immunology

Spike-specific memory B cells increase up to 6 months after infection, suggesting long term protection. IgG antibody and T cell responses were stable 3-4 months after SARS-CoV-2 infection, whilst IgA levels decayed. Another study found that T cell responses remained stable, whilst humoral responses decayed. A separate study of healthcare workers with mild disease found that antibody levels reduced between three weeks and three months after infection.

Cross-reactive antibodies against seasonal coronaviruses that cause the common cold were boosted after SARS-CoV-2 infection, but do not protect from COVID-19.

Mucosal-associated invariant T cells were shown to be linked to severe COVID-19, as was the timing of the immune response. Megakaryocytes and monocyte subsets may contribute to the cytokine storm seen in some severe patients.

Animal hosts

A coronaviruses related to SARS-CoV-2 was found in five different Rhinolophus acuminatus bats in a Thai cave. SARS-CoV-2 neutralising antibodies were detected in bats in the same colony, showing that these bat coronaviruses have a wide geographic distribution of at least 4800 km.

The spike protein from a coronavirus found in pangolins was found to bind to human and pangolin ACE-2, although the structure resembled a bat coronavirus more than SARS-CoV-2.

Virology

Regions of the spike protein that affect viral entry were identified using a CRISPR screen.

Risk factors

The REACT-2 study of 100,000 people in England found that healthcare workers and people of Black and South Asian ethnicity were more likely to be infected with SARS-CoV-2, based on serology, but had the same infection-fatality ratio as people of white ethnicity. A study of US care homes found that there were higher death rates in those with fewer white residents.

SARS-CoV-2 infects ex vivo pancreas cells, and was detected in the pancreas in infected patients, which may contribute to the metabolic dysregulation seen in COVID-19 patients.

52% of more than 800 homeless people in France tested positive for SARS-CoV-2 by serology.

Climate

Global power sector carbon dioxide emissions have shown a substantial decline during the pandemic. A small role was found for local climate conditions in COVID-19 outbreak severity, but non-pharmaceutical interventions had a much greater impact.

Testing

High income neighbourhoods saw more COVID-19 testing than poorer neighbourhoods in Massachusetts. As of August 2020, only 2% of Virginia residents tested positive for COVID-19, with more cases amongst those of Hispanic ethnicity. A rapid diagnostic test based on isothermal rolling circle amplification was developed.

Publishing

COVID-19 papers were accepted within 13 days of submissions, on average, compared to more than 100 days for non-COVID-19 papers. Such papers also tended to have lower methodological quality.

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.