5th January 2021 - the COVID-19 coronavirus compendium

Vaccines, anti-virals, and re-infection

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My first blog of 2021 is in reality the final blog from 2020, as I failed to write a single compendium in December. What follows is therefore a selection of research from the last month of last year, with a few new papers from this week. I hope to continue this blog in the early months of 2021, less often than before, but every few weeks.

The main news of December was the publication of the phase 3 trials of three coronavirus vaccines: two mRNA vaccines and a recombinant Adenovirus vector, all of which were effective. We also saw the main results of the RECOVERY trial, which found that none of the drugs tested had a significant effect, and an important study showing that re-infection is rare, at least 6 months after the first infection.

Transmission

An analysis of the outbreak in Wanzhou, China, found that 75% of transmission events were in those without symptoms, with asymptomatic infections representing one third of cases. Transmission risk was greatest in the first 5 days after infection, which is often before symptoms appear.

An analysis of viral genomes from Boston found that a superspreading event at a conference produced sustained community transmission; another superspreading event in a skilled nursing facility led to many cases in this population, but not beyond that.

A screening programme by the UK Office of National Statistics (ONS) found that more than 1% of their sample tested positive for an active infection by RT-PCR from October. People 17-24 years were most likely to be infected and many had no symptoms.

A study of almost 1000 pets in Italy found that 3% of dogs and almost 6% of cats had antibodies against the virus, although none that were PCR positive. Their role in transmission, if any, is not known.

An estimated 20% of the Iranian population tested positive for COVID-19, according to a serology screen, with more than 70% testing positive in the city of Rasht. There seemed to be little variation by occupation, including in those thought to be at high risk.

Social distancing

A Bayesian hierarchical model estimated the effects of different non-pharmaceutical interventions on reducing transmission between January and May 2020. Closing schools and universities, limiting gatherings to 10 people or less, and closing face-to-face business all reduced transmission considerably, whereas stay at home orders had little additional effect.

SARS-CoV-2 was introduced into Scotland on at least 283 occasions during February and March 2020, mainly from Italy and Spain, with community transmission 3 weeks before any control measures were introduced. Earlier travel restrictions would therefore likely have been effective. The effects of the UK lockdown on deaths was modelled, with an estimated 22% reduction in the reproductive number.

An analysis of the outbreak in New Zealand found that lockdown was highly effective and reduced the reproductive number from 7 to 0.2 within 1 week. Similarly, only 19% of virus introductions resulted in ongoing transmission, which reduced and ultimately halted virus spread.

A largely uncontrolled outbreak in Manaus, a city of 2 million in the Brazilian Amazon, resulted in an estimated 76% of the population being infected by October, compared to 29% in São Paulo.

Testing

A four antigen multiplex assay for serological testing was more accurate than testing a single antigen, especially months after infection. A coronavirus antigen microarray was developed for improved serological testing.

A portable device was developed to test for SARS-CoV-2 in 17 minutes, using RT-PCR via plasmonic heating, as was a lateral flow device which works within 1 hour. A high-throughput proteomics array was developed to test more than 500 samples per day.

At risk groups

People with HIV in the UK had a higher risk of death from COVID-19, according to a study of almost 15,000 COVID-19 deaths, 25 of which were in people with HIV. The increased risk was still seen after adjusting for age, sex, deprivation, ethnicity, smoking, and obesity.

Outbreaks were uncommon in schools in the UK, with most individual cases being acquired in the community, rather than in an educational setting.

A study in Scotland confirmed that those with diabetes are at an increased risk of fatal COVID-19. Patients were hypertension showed a higher expression of proinflammatory cytokines in their airways during COVID-19, which may exacerbate disease.

COVID-19 patients were 3 times as likely to be hospitalised as those with influenza, and in-hospital mortality was higher, although risk factors differed considerably, according to a study of more than 100,000 people in France.

Individual and community level risk factors for severe COVID-19 were calculated and used to identify relatively small fractions of the population that might experience a high proportion of deaths. Another study of more than 3 million cases confirmed that men were 3 times more likely to require intensive care treatment than women, and more likely to die.

The aging lung was analysed and shown to differ in the expression of several genes, which may affect susceptibility to disease.

Vaccines

The phase 3 trials of three vaccines, now approved in some countries, were published. The trial of the mRNA vaccine, BNT162b2, produced by BioNTech with Pfizer, included more than 43,000 participants. There were 8 cases of COVID-19 in the vaccine group, compared to 162 cases in the placebo group, giving an efficacy of 95%. Of 10 cases of severe COVID-19, 1 was in the vaccine group.

The phase 3 trial of the Moderna vaccine, mRNA-1273, had more than 30,000 participants. COVID-19 symptoms were confirmed in 185 participants in the placebo group and just 11 in the vaccine group, giving an efficacy of 94%. Severe COVID-19 occurred in 30 participants, including one fatality, all in the placebo group.

The ChAdOx1 nCoV-19, based on a recombinant chimp adenovirus, included more than 23,000 participants across three study sites in the UK, Brazil, and South Africa. Of those who received the standard dosing, there were 71 COVID-19 cases in the control group compared to 27 in the vaccine group, giving an efficacy of 62%. However, a small group that received a lower dose followed by the standard dose had an efficacy of 90%. All of the 10 hospitalised COVID-19 cases, including 1 death, were in the control group.

Another study of the phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine found that a booster dose improved antibody responses, and a third study described the immune response to the vaccine in detail. This vaccine has been approved for use in the UK.

A new vaccine, based on recombinant VSV, was developed and shown to protect Syrian hamsters form challenge.

Self-reported likelihood of getting a COVID-19 vaccine declined in the US, from 74% in April to 56% in December, and was especially low for Black individuals and those with low educational backgrounds. 35% and 31% of the populations of Ireland and the UK were found to have some vaccine hesitancy, which was associated with mistrust in traditional news sources.

Anti-virals

The RECOVERY trial in more than 30 countries found that remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on COVID-19 patients.

An antibody cocktail, REGN-COV2, reduced viral load in a small study of 275 COVID-19 patients. Monoclonal antibody LY-CoV555 did not demonstrate efficacy among hospitalised COVID-19 patients, and the trial was stopped early.

Baricitinib, a Janus kinase inhibitor, was combined with remdesivir and found to be superior in accelerating improvement in a study of 1000 COVID-19 patients. Tocilizumab treatment reduced the likelihood of mechanical ventilation but did not improve survival in a small trial of hospitalised people, most of whom were Black or Latino.

A ribonucleoside analogue, MK-4482/EIDD-2801, was effective at reducing viral load and transmission in infected ferrets. The drug is being tested in humans.

A case study described successful remdesivir use in a patient with X-linked agammaglobulinaemia, a genetic condition that prevents them from producing antibodies.

Immunology

A screen found that of 1265 seropositive healthcare workers only 2 tested positive for a repeat infection by RT-PCR in the following 6 months, showing protection from re-infection.

Afucosylated IgG antibodies are naturally produced against infection, but are overrepresented in COVID-19 patients, amplifying cytokine release and acute phase responses. Severe COVID-19 was associated with higher antibody production, and these sera continued to neutralise both D614 and G614 variants. The antibody response in 1850 COVID-19 patients was analysed in detail

Type I interferon responses were delayed and diminished in COVID-19 patients, in comparison to influenza.

Neuroscience

SARS-CoV-2 RNA and protein were identified in the nasopharynx and brain of COVID-19 patients, with the virus proposed to enter the nervous system via olfactory mucosa. CNS abnormalities were seen in a small number of children.

Virology

SARS-CoV-2 ORF3a blocks the formation of autolysosomes. 104 human proteins that interact with the virus were identified and characterised, as were host factors required for growth of common cold coronaviruses. TMEM41B was identified as a critical pan-coronavirus host factor in another screen.

Receptor

The D614G mutation, seen in many countries worldwide, alters the conformation of the spike protein and enhances protease cleavage.

Model systems

COVID-19 disease was compared in rhesus macaques, baboons and old marmosets, with both macaques and baboons showing similar disease to humans. Transgenic mice expressing human ACE-2 by the human cytokeratin 18 promoter were found to be highly susceptible to infection.

Mental health

Symptoms of depression and anxiety were highest at the start of lockdown in the UK, and decreased since then, according to a regular survey of 70,000 adults.

Both men and women in Turkey reported less sexual intercourse during the pandemic, with an increase in solitary sexual behaviour. Couples that spent more time together reported better sexual function.

Pregnancy

There was no evidence of an increase in stillbirths during the COVID-19 pandemic in England, or in Philadelphia, despite some individual hospital data suggesting this.

Clinical findings

A study of more than 200,000 COVID-19 patients found that fever, cough, and fatigue were the most common symptoms, but that loss of taste and smell three weeks prior to testing was the most discriminative symptom.

A small study from Italy found that 87% of COVID-19 patients reported persistence of at least 1 symptom, particularly fatigue and shortness of breath, sometimes known as “long COVID”.

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.