29th January - the COVID-19 coronavirus compendium

Regional differences, opioid deaths, and children

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In the past two weeks we learnt that the fatality rate for COVID-19 differs by region in Brazil, that opioid deaths amongst Black people in the US increased during the pandemic, and that children in Germany were three times less likely to be infected with SARS-CoV-2 as their parents. 

Transmission

Seroprevalence of SARS-CoV-2 was low in parents in southwest Germany, and even lower in their children, suggesting that children do not play a key role in transmission.

Sustained community transmission of SARS-CoV-2 was underway in Lombardy, Italy, before the first case was detected, based on genome sequencing of virus isolates in this hard hit region.

An analysis of almost 30,000 households in Wuhan, China, found that the virus mainly spread before symptoms developed, with a secondary attack rate of almost 16%. This study found that asymptomatic cases were less infectious than those with symptoms, conflicting with data from other places.

A genomic analysis of the outbreak in Russia found that there were at least 67 introductions of the virus in March and April, only one of which was from China, leading to at least 9 distinct viral lineages circulating.

Social distancing

Mask wearing combined with social distancing is effective at transmission control, according to a large survey from the USA. Government mask mandates did not correlate with self-reported mask wearing, questioning their effectiveness. A decrease in adherence to non-pharmaceutical interventions in the US was observed throughout the course of 2020; an exception to this was mask wearing, which increased.

A model of the outbreak in São Paulo, Brazil, found that a 5-10% increase in the proportion of people who strictly follow guidelines is needed. After this, social distancing can be gradually relaxed every 80 days, according to their model.

Immunology

An analysis of memory B cells found that they persist at least 6 months after infection, despite the levels of serum antibodies waning. Rhesus macaques infected with SARS-CoV-2 developed robust germinal centres, indicative of long lasting memory immunity.

Several studies looked at the effects of spike mutations on antibody binding. A map of mutations identified several that affect binding by the REGN-COV2 cocktail and the antibody LY-CoV016. Mutations in the spike protein were engineered into a VSV pseudovirus, and showed that S477N was resistant to neutralisation by multiple monoclonal antibodies and E484K escaped neutralisation by convalescent sera. A third study found that the N439K spike mutation, seen in some lineages, confers resistance to some antibodies, but does not cause more severe disease.

Patients with severe COVID-19 fail to mount an adequate interferon response, with a lack of interferon stimulated genes, compared to mild patients. Severe patients instead show very high antibody titres and have a lower viral load than mild patients.

Vaccines

A vaccination strategy model was developed and showed that targeting those 20-49 years reduced cases most effectively, but targeting those over 60 years had a greater impact on lives lost. Use of serological tests to vaccinate those who had not been naturally infected also boosted the impact of the vaccination programme.

A whole virion vaccine, BBV152, given with one of two adjuvants was safe and immunogenic in a phase 1 trial. A vaccine that displays the spike receptor binding domain on a virus-like particle was developed and shown to be immunogenic in mice and pigs. A two-component protein-based nanoparticle vaccine, again using the spike protein, was shown to be immunogenic in mice, rabbits, and cynomolgus macaques and protected macaques from a high dose challenge.

Treatments

The drug plitidepsin (aplidin), which targets the host translation machinery, had potent anti-viral activity against SARS-CoV-2, as well as reducing viral replication in the lungs of infected mice, showing its potential use in humans, although further studies are needed.

For patients with severe or critical COVID-19 tocilizumab treatment may have increased mortality, although the trail in Brazilian hospitals was stopped early because of the increase in deaths. An interleukin-1 antagonist, anakinra, was not effective against COVID-19 in a small clinical trial.

Two small molecules with an indoline and indole moiety were identified that block the infectivity of SARS-CoV-2  in vitro. A small molecular inhibitor of the coronavirus PLpro was identified and its binding site characterised, paving the way for more inhibitors. The structural basis for remdesivir activity on viral replication was shown.

A rationally engineered monoclonal antibody displayed cross-neutralising activity against different coronaviruses and bound and neutralised the viruses that cause SARS and COVID-19. Treatment with two monoclonal antibodies was found to reduce viral load, but they did not work when administered individually. Another study found that a combination of two antibodies effectively neutralised the virus in vitro and prevented it from escaping.

Risk of severe disease

Schizophrenia was associated with an increased risk of death from COVID-19; mood and anxiety disorders were not. Smoking was associated with higher odds of hospitalisation and death from COVID-19, with those with more than 30-pack years having the greatest risk. Previous research had shown some protective effects from smoking, which were not seen in this study.

The main burden of seasonal coronaviruses falls on children, unlike SARS-CoV-2 which mainly affects older people, according to a study from Belgian hospitals from 2015-2020. A prediction model of severe disease was developed based on data from 1003 patients in France.

Virology

The furin-cleavage site, found in SARS-CoV-2 but not in other group 2B coronaviruses, was shown to be essential for virulence, as a mutant virus lacking the site was attenuated. A cryo-EM structure of SARS-CoV-2 Nsp15, which binds and processes RNA, was published. The N protein of coronaviruses was shown to drive phase separation with RNA, allowing the formation of ribonucleoprotein complexes.

Energy

The COVID-19 pandemic has exacerbated energy insecurity, especially for Black and hispanic households and those with young children.

Diagnostics

A new class of protein-based biosensor was developed and used to detect antibodies against SARS-COV-2, as well as the spike protein directly.

Technology

The effectiveness of a contact-tracing app, Radar Covid, was assessed during an outbreak in the Canary Islands in June and July 2020. The app detected more than 6 contacts per case, many of whom were strangers, but the follow up rate was low. A similar app in Germany was downloaded by people at risk of severe disease, but not downloaded by those at an increased risk of catching the virus.

Healthcare

In a national survey in the US, 41% of respondents reported forgoing medical care during the pandemic. Radiotherapy treatment for cancer fell significantly in England during the pandemic, although it’s use increased for some cancers, most likely as an alternative to surgery. The number of suicides in Massachusetts did not appear to have increased during 2020, compared to 2019, despite the mental health challenges of lockdown.

The number of opioid overdose deaths during the COVID-19 pandemic increased in non-Hispanic Black individuals while decreasing amongst non-Hispanic white individuals, highlighting racial disparities. A 7-fold increase in alcohol-based sanitizer-related eye exposure in children was observed in 2020 compared to 2019.

Fatality rate

A large analysis of hospitalised cases in Brazil found that the vast majority of patients had underlying health conditions, with a high in-hospital fatality rate of 38%. The in-hospital mortality rate for adults under 60 years varied by region, at 31% in the poorer Northeast, compared to 15% in the South, highlighting health inequalities.

Clinical findings

One fifth of COVID-19 patients had posttraumatic stress 4 months after discharge, and more than half had a significant reduction of lung capacity.

Ben Johnson

Head of Communities & Engagement, Springer Nature

I gained my first degree in virology from the University of Warwick and a PhD in influenza virus immune evasion from Public Health England and the University of Reading, UK. My research interests then moved on to smallpox vaccines, viral ion channels, and cell adhesion, while a postdoc at Imperial College London. I joined open access publisher BioMed Central in 2011 as an Acquisitions Editor and then Associate Publisher, and was responsible for launching new journals, including Microbiome, Zoological Letters, and Movement Ecology. I have been Head of Communities & Engagement at Springer Nature since 2016, running our online community blogs, and a Consulting Editor at Nature Medicine since June 2020, handling COVID-19 papers. I am based in our London office.

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