Researchers identify genetic differences associated with severe Covid

‘These results explain why some people develop life-threatening Covid-19, while others get no symptoms at all,’ says expert behind new study

Genetic differences that put people at higher risk of severe Covid have been identified by researchers.

In a study of more than 57,000 people, 16 new DNA changes were discovered which are associated with severe Covid-19.

Researchers from the GenOMICC consortium – a global collaboration to study genetics in critical illness – led by University of Edinburgh in partnership with Genomics England, made the discoveries by sequencing the genomes of 7,491 patients from 224 intensive care units in the UK.

Their DNA was compared with 48,400 other people who had not had coronavirus, and that of a further 1,630 people who had experienced mild Covid.

The variation in the 16 genes occurs naturally in the immune, inflammation and coagulation pathways of the body. These differences influence the seriousness of Covid disease.

The findings, published in the Nature journal, demonstrate how a single gene variant was enough to increase a patient’s risk of severe disease, and suggest treatment and drugs could be tailored to help manage Covid in its early stages.

Professor Kenneth Baillie, the project’s chief investigator and a consultant in critical care medicine at University of Edinburgh, said: “Our latest findings point to specific molecular targets in critical Covid-19.

“These results explain why some people develop life-threatening Covid-19, while others get no symptoms at all.

“But more importantly, this gives us a deep understanding of the process of disease and is a big step forward in finding more effective treatments.

Professor Sir Mark Caulfield from Queen Mary University of London, formerly chief scientist at Genomics England and co-author on the study, said: “As Covid-19 evolves, we need to focus on reducing the number of people getting seriously ill and being hospitalised.

“Through our whole genome sequencing research, we’ve discovered novel gene variants that predispose people to severe illness – which now offer a route to new tests and treatments, to help protect the public and the NHS from this virus.”

According to the researchers, not everyone will have all the DNA changes identified and therefore some people will have a greater or lesser tendency to have severe outcomes.

Sir Mark explained: “I think what we can say today is that these variants do denote people that are more likely to have a critical illness.

“And if we knew about them earlier in the course of their illness, we might be able to consider early intervention with some of the medicines we’ve been talking about, such as dexamethasone or others to try and prevent an adverse outcome.”

However, the experts suggest that while doctors might be able to make predictions about patients based on their genome, the technology is not there yet.

Prof Baillie said: “I think most clinicians would tell you that it was completely bewildering the first time we saw patients with this disease because we’ve never seen it before.

“And there was a really palpable sense that we didn’t understand it and we didn’t know what to do.

“And now you have three effective treatments to suppress people’s immune response and 23, in total, robust genetic associations with identifying the mechanisms of disease – an extraordinary rate of progress.”

Commenting on the study, Andrew Mumford, a professor of haematology at the University of Bristol, said: “Understanding the genomic basis of the response to Covid-19 has the potential to improve prediction of whether individual patients will develop severe disease.

“Some of the genes identified in this study are already known to be targets for existing therapies for Covid-19. Others represent novel new drug targets that are exciting candidates for future clinical study.”

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