21st August - the COVID-19 coronavirus compendium

A new variant of SARS-CoV-2, racial disparities in hospitalised cases but not deaths, and more sensitive serology tests

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This week, a new variant of SARS-CoV-2 in Singapore was shown to be less virulent, racial disparities were found in the numbers of hospitalised patients with COVID-19, but no differences were observed in deaths, and serology tests against the nucleoprotein and two other proteins of unknown function were found to be more sensitive than the standard serology tests against the spike protein.

Genomics

A 382-nucleotide deletion in ORF8 was identified in SARS-CoV-2 samples from Singapore and associated with a milder form of disease. 30% of isolates had the variant strain, or a mix of variant and wild-type; none of the 129 patients with the new variant required oxygen, compared to 28% of infections with wild-type virus.

At-risk groups

Black, Hispanic, American Indian, and Alaskan Native people were disproportionately likely to be hospitalised with COVID-19, according to a study of almost 50,000 hospitalisations across 12 US states. For example, Black people make up 13% of Ohio’s population, but 32% of hospitalisations. White people and Asian people were less likely to be hospitalised.

In contrast, there was no difference in in-hospital mortality between White and Black COVID-19 patients, in a cohort study of more than 11,000 people across 12 US states. Black patients were younger and more likely to be women than White patients. Only 12 US states recorded hospitalisations by ethnicity, although two more have recently started reporting this data.

Transmission

7 people with SARS-CoV-2 boarded a flight from Tel Aviv to Frankfurt, resulting in two likely transmission events. Both new cases were seated within two rows of the infected passengers and the authors speculate that cabin airflow from ceiling to floor and from front to rear may have contributed to the low transmission rate. None of the passengers wore masks.

Community health workers in India are at risk of catching SARS-CoV-2 due to their visits to potentially sick patients in their homes. 12 health workers were infected early in the epidemic, comprising 19% of the workforce, which dropped to none after wearing of face shields was mandated, showing their effectiveness. In-person visits by obstetricians to expectant mothers were not associated with an increased risk of catching SARS-CoV-2, according to a study from Massachusetts.

Breast milk from 18 women with SARS-CoV-2 was tested and none found to contain live virus, although one briefly tested positive for viral RNA. This suggests that transmission from mother to baby via breast milk is not a route of transmission.

A case of human-to-cat transmission was identified in Belgium; both tested positive for the virus and the cat developed a severe respiratory syndrome. Both cat and human recovered.

Diagnostics

Current serology testing measures antibodies against the coronavirus spike protein, which is also the target for most vaccines. However, a new study found that sensitivity was greatest when measuring antibodies against the nucleoprotein, with levels peaking earlier and at higher levels. Two other antigens, ORF3b and ORF8, also performed well and were stable over long periods of time, and so can be combined in a serology test for maximum sensitivity, to overcome false negative results. The function of ORF3b and ORF8 in SARS-CoV-2 infection is not known.

Molecular testing by RT-PCR (often called test and trace) can reduce transmission, but alone is not sufficient to keep the reproductive number below 1, according to a modelling study.

A machine learning algorithm was able to detect COVID-19 in CT scans, with a false positive rate of 10% in patients with other pneumonias.

Treatments

Tocilizumab is an interleukin-6 inhibitor, and as such may be useful in reducing the hyper-inflammatory state seen during late, severe COVID-19. A retrospective observational study found that patients treated with tocilizumab had reduced mortality compared to those that were not treated, suggesting it may be a useful therapy for late-stage disease.

Metformin is a common treatment for diabetes, which is an important risk factor for COVID-19. Metformin use was associated with increased acidosis in COVID-19 patients, but was not associated with an increased mortality. Indeed, metformin use was associated with a reduced risk of heart failure and reduced inflammation, supporting continued use by diabetics during the pandemic.

Vaccines

Most of the coronavirus vaccines in clinical trials take a modern approach, comprising mRNA or adenovirus vectors expressing the immunogenic spike protein. These are quick to adapt for a new disease, but are not yet proven to work. A more traditional approach is to grow the live virus and inactivate it with β-propiolactone. A new study does exactly this and shows that this inactivated vaccine was safe and immunogenic in two separate trials, published together. Phase 3 trials, which test efficacy, are ongoing.

Another chimpanzee adenovirus vector expressing the SARS-CoV-2 spike protein (ChAd-SARS-CoV-2) was tested, this time in mice expressing human ACE-2. An intramuscular dose protected from lung infection and pathology but did not prevent viral replication. In contrast, an intranasal dose almost completely prevented viral replication in the upper and lower respiratory tract.

Immunology

The immunopathogenic nature of a new multisystem inflammatory syndrome in children was described. Not all of the children tested positive for SARS-CoV-2, but the majority did, and those that were seropositive had a worse outcome, strongly suggesting that it is a rare response to the virus. The syndrome is similar to, but distinct from, Kawasaki disease.

A blood immune signature in COVID-19 patients was identified, with some traits predictive of severity.  The T cell response to infection was also described in another paper; and the absence of germinal centres after infection was shown, which may explain why the humoral immune response appears to be short-lived.

Levels of neutralising antibodies in COVID-19 patients with mild disease varied considerably, with older patients generally having higher titres than younger patients.

Structure

The structure of intact SARS-CoV-2 virions was visualised using cryo-EM, showing the confirmation of the spike protein on the surface. Another study looked at the spike protein in situ, rather than an expressed recombinant form, and found unexpected flexibility. The spike contained three hinges that the authors propose allows it to scan the host cell surface, shielded by an extensive glycan coat.

Receptor

The glycosylation of the coronavirus spike protein and the ACE-2 receptor are both described, which may help to understand this important interaction.

Knowledge

Medical information for the public should be easy to understand; in the US this means no higher than an eight-grade reading level. However, an assessment of 18 COVID-19 information pages found that they regularly exceeded this reading level, making the information difficult to understand and limiting their effectiveness.

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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