25th September – the COVID-19 coronavirus compendium

Re-infection with common cold coronaviruses, inborn errors of the interferon response, and deaths due to pollution

Like Comment
Read the paper

This post is a little later than usual due to my first holiday since February. It was certainly nice to have a break from work, but I don’t think any of us can have a real break from COVID-19 for a while. There has been a lot of exciting research published since I went on holiday, so here are the last two weeks’ research highlights.

In the past two weeks we learnt that re-infection with seasonal common cold coronaviruses is common after 12 months, that genetic mutations in the interferon response predispose some people to severe infection, and that thousands of deaths in China and Europe have been averted due to reductions in air pollution during lockdown.

Immunology

35 years of infection data for 10 healthy individuals found that re-infection with seasonal coronaviruses is common 12 months after infection. Increases in the serological immune response to the four known season coronaviruses, HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 were used to measure re-infection. The number of coronavirus infections over the time period ranged from 3 to 17, with the duration between infections between 6 and 105 months. Infections were rare between June and September, confirming that coronaviruses are usually seasonal. It is important to note that these infections were uniformly mild or asymptomatic, and the implications for SARS-CoV-2 are unclear.

The vast majority of SARS-CoV-2 patients with mild disease seroconvert, producing robust antibody responses, according to a study of more than 1300 New York residents. Levels of antibodies decreased over 60 days, in a small study of 19 participants with COVID-19.

Three SARS-CoV-2 proteins interfere with the type I interferon system by distinct mechanisms.

Genomics

10% of patients with severe COVID-19 had auto-antibodies against parts of the interferon response, and had these antibodies before infection, suggesting that inborn errors of immunity are responsible for severe disease in around 3% of women and 12.5% of men. A second study found that rare loss of function mutations in TLR3 and TLR7, also parts of the interferon response, can also underlie severe COVID-19.

Masks

Surgical masks and N95 respirators were both effective at reducing particle emission when speaking and coughing, confirming their effectiveness. Cloth masks could not be assessed as they constantly shed small particles from the fabric, and so their effectiveness remains unclear.

Treatments

Two ultra-potent antibodies were isolated and used to treat infection in hamsters. A second study found that monoclonal antibodies protected hamsters from a lethal infection, but some of the neutralising antibodies also recognised self-antigens, which may limit their use. Convalescent plasma from recovered patients was effective at reducing mortality in a study of 39 COVID-19 patients in New York.

A free fatty acid pocket was identified in the coronavirus spike protein; treatment with linoleic acid reduced ACE-2 binding and reduced viral replication in cells when combined with remdesivir.

Favipiravir is rapidly incorporated into coronavirus genomes by the viral RNA dependent RNA polymerase, causing lethal mutagenesis, and suggesting it could be used as an anti-viral.

The use of ECMO remains controversial; a new study examined its use and effects on mortality, and recommended it should still be considered. Yet another study found that hydroxychloroquine treatment was not associated with a reduced risk of catching SARS-CoV-2, this time in veterans who took the drug to treat rheumatic disease.

Transmission

Two large seroprevalence surveys were carried out in cities across Brazil in May and June, and found that overall prevalence increased from 1.9% to 3.1% in this time, and ranged from 0% to 25%. Prevalence was especially high in 11 cities along a 2000 km stretch of the Amazon River and in the North East, with rates highest amongst indigenous people, those living in crowded conditions, and in the poorest people.

Commuting has reduced during the pandemic. In New York City, the boroughs with the greatest reductions in traffic out in the morning and traffic in in the evening were associated with lower cases of COVID-19; prevalence is lowest in Manhattan and highest in South Queens. This suggests that “work from home” policies are effective at reducing transmission.

A modelling study of transmission in Hong Kong estimated that 19% of cases caused 80% of local transmission, something the authors refer to as super-spreading events.

8% of US dialysis patients tested positive for SARS-CoV-2 by serology, ranging from 3.5% in the west to 27% in the north-east. Residents of mainly Black and Hispanic neighbourhoods were more likely to test positive and those living in counties with strict mobility restrictions less likely to test positive. 1.8% of blood donations from the American Red Cross tested positive for antibodies against SARS-CoV-2. The virus is not transmission by transfusion. Seroprevalence in San Francisco was less than 0.5%, according to a study which used three separate assays. Testing in areas with low seroprevalence relies on highly accurate tests such as these.

Those who wear glasses every day were less likely to be infected with SARS-CoV-2, as shown by 6% of COVID-19 patients wearing glasses, compared to a prevalence of myopia of 32% of the local population of Suizhou, China. The authors speculate that those who wear glasses are less likely to touch their eyes, which can be a route of transmission.

Diagnostics

A point of care cartridge-based diagnostic test, CovidNudge, was developed and has been used in UK hospitals since May. A new serology test based on antigen coated beads was developed, which could allow rapid testing of seroprevalence. Five immunoassays were tested for sensitivity and specificity. A CRISPR-Cas12a assay was developed to detect viral RNA, as was a one-pot isothermal ligation and transcription. RT-PCR can be performed on patient samples without a separate RNA extraction step, according to a study of more than 500 samples.

Coronavirus RNA could be found in wastewater around 2 days before local epidemic peaks, showing its potential use to track the outbreak.

AI-guided assessment based on CT scans was used to triage patients at Tongji hospital in China. A mortality predictor was developed using data from New York.

At risk groups

Those with COPD or asthma do not appear to be at as much an increased risk for severe COVID-19 as one would expect for a respiratory virus, perhaps because of their use of corticosteroids. A large study of almost 150,000 people, using the OpenSAFELY platform of UK GP data, found that corticosteroid use by asthma and COPD patients did not affect the risk of COVID-19 death, when controlling for underlying differences between the groups.

Three studies looked at ethnicity as a risk factor for fatal COVID. Two studies found that Black and Hispanic people in the US were more likely to test positive for SARS-CoV-2, but no more likely to have a fatal infection, despite having a higher likelihood of pre-existing comorbidities. One of these studies also found that poverty was associated with severe disease. A third study confirmed that Black and Hispanic ethnicity was not associated with mortality, and also found that no association for obesity, COPD, hypertension, and smoking; old age was the main predictor of mortality in this study of almost 90,000 veterans.

A study of COVID-19 in homeless people in England found that cases can be high even when the incidence is low in the general population, and estimated that transmission prevention measures in hostels could prevent hundreds of deaths in this vulnerable population.

The factors that increase risk of death in cancer patients with COVID-19 were investigated, with the Eastern Cooperative Oncology Group score of ≥2 the only predictor of death. Cancer treatment had to be adjusted in many patients.

Mental illness is not a risk factor for catching the virus, according to a study of more than 200,000 people in South Korea. Children were less likely to test positive for the virus in Milan, with just 1% testing positive, compared to 9% of adults. Non-English speakers in the US were less likely to have been tested for SARS-CoV-2, but more likely to have a positive test result.

Markers of severe illness

Elevated red blood cell distribution width independently predicted mortality risk, in a cohort study of more than 1600 patients.

Healthcare

Diagnoses of common physical and mental health conditions decreased during the pandemic, suggesting that people are not presenting to medical professionals for fear of catching the virus. Hospital admissions for acute myocardial infarction also decreased in a study from France.

Malaria mortality could double if control measures are interrupted due to the COVID-19 pandemic.

Pollution

An estimated 24,000 deaths have been averted in China due to reductions in PM2.5 pollution during lockdown, with a further 2190 deaths averted in Europe.

Model systems

A mouse-adapted SARS-CoV-2 caused lethal infection and can be used as an animal model. Syrian hamsters infected with the virus have a subclinical infection, which may be useful to understand asymptomatic infection in humans.

SARS-CoV-2 triggers an inflammatory response in stem cell derived alveolar type 2 cells, and can infect stem cell derived neural cells in vitro, where it predominates in the Choroid Plexus Epithelium.

Clinical findings

SARS-CoV-2 was found outside the lungs in patients who had a fatal outcome, but as the disease developed less evidence of virus was found. There was also evidence of widespread inflammation, especially the continued presence of neutrophils.

Pregnant mothers who tested positive for SARS-CoV-2 were more likely to have pre-eclampsia, but no increased risk of pre-term birth.

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.

No comments yet.