September 28, 2021

expert reaction to study looking at a gene in people called OAS1 and severity of COVID-19

A study published in Science looks at the presence of different versions of a gene called OAS1 and COVID-19 severity.

Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“This detailed and insightful study examines human genes specifying natural defences to viral infection.  It identifies a small handful of genes capable of inhibiting the growth of SARS-CoV-2, focussing on one called OAS1 that senses viral RNA.  This gene exists to two forms in humans, a long form that can block SARS-CoV-2 growth and a short form that does not.  Examination of over 400 patients hospitalised with COVID-19 showed that individuals that make only the short form are at increased risk of severe illness following virus infection.  Other kinds of coronavirus appear to have adapted to avoid OAS1 mediated defences so the authors of the present study raise the possibility that with time this might also happen with SARS-CoV-2.  This could give rise to a virus with an increased likelihood of causing severe disease.  However, OAS1 is not the only human gene providing natural protection against the virus.  Moreover, one would expect that any viruses resistant to OAS1 would still be fully susceptible to vaccine induced immunity.”

Dr Alexander Edwards, Associate Professor in Biomedical Technology, Reading School of Pharmacy, University of Reading, said:

“The immune system is remarkable – and one of the most remarkable features is the multiple layers of defences we have against infection.  Another feature of human immunity is the variability between different individuals, which helps us respond robustly to highly variable infections – but this can also lead to different outcomes when individuals are infected.

“This new study elegantly identifies one particular defence mechanism that – depending on exactly how it is configured in the individual – is more or less able to protect from the virus that causes Covid-19.  All the layers of our immune system work together, and we need all layers because infections can escape so many parts of the defences.  As we continue to unravel these layers under the microscope of modern immunology and genetics, our chances of responding improve, helping to know how to protect vulnerable people, and how to best use the medicines we do have.”

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“This research gives us interesting insight into how and why a single-letter change to the genetic code of some people influences how severely affected they may be by COVID-19.  It’s important to understand that this is not a new drug, and it does not offer us an immediate avenue for a novel treatment, although that could change in the long term.

“This change alters a gene which makes OAS1, allowing it to get to parts of an infected cell where it can more easily detect the presence of the coronavirus.  In doing that, it can better activate the cell’s defences against the virus.

“This will not be the one and only factor involved in COVID-19 susceptibility, and people with complicating conditions like high blood pressure, diabetes or who are overweight, will remain at relatively high risk, regardless of which version of OAS1 they have.  As the paper points out, there have been plenty of people with the more effective version of OAS1 who have ended up in hospital, they just generally have better outcomes.

“Scientists and doctors now need to watch out for a potential new variant of the COVID-19 which could evade OAS1 defences, but it’s by no means certain that such a version of the virus will ever arise, or that if it did, it would pass the evolutionary fitness test of being able to spread more easily.”

‘A prenylated dsRNA sensor protects against severe COVID-19’ by Arthur Wickenhagen et al. was published in Science on Tuesday 28 September 2021.

DOI: 10.1126/science.abj3624

https://www.science.org/doi/10.1126/science.abj3624

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