The world’s largest study into the genetics of severe COVID-19 has found new details about some of the biological mechanisms behind the disease.
The GenOMICC consortium research involved more than 57,000 people and identified 16 new genetic variants associated with severe COVID-19, some of which relate to blood clotting, immune response and intensity of inflammation.
Led by the University of Edinburgh, the GenOMICC consortium is a global collaboration to study genetics in critical illness.
Chief investigator Professor Kenneth Baillie, consultant in critical care medicine at the 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.
“It is now true to say that we understand the mechanisms of COVID better than the other syndromes we treat in intensive care in normal times – sepsis, flu, and other forms of critical illness. COVID-19 is showing us the way to tackle those problems in the future.”
For this study, which is published today in *Nature*, the team worked with Genomics England to sequence 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 COVID-19, participants in Genomics England’s 100,000 Genomes Project and 1,630 people who had experienced mild COVID.
The team created a precise map to identify genetic variation linked to severity of COVID-19, finding key differences in 16 genes in the ICU patients, when compared with the DNA of the other groups.
They also confirmed seven other genetic variations that had already been associated with severe COVID-19 in earlier studies from the same team.
The team found interferon alpha-10, a single gene variant that disrupts a key messenger molecule in immune system signalling, increased a patient’s risk of severe disease.
This, they say, highlights the gene’s key role in the immune system and could mean treating these patients with interferon may help to manage the early stages of the disease.
The study also found that variations in Factor 8, genes that control the levels of a central component of blood clotting, were associated with critical illness in COVID-19, which could explain some of the clotting abnormalities that are seen in severe cases.
Co-author Professor Sir Mark Caulfield from Queen Mary University of London, formerly chief scientist at Genomics England, 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.”
Dr Rich Scott, chief medical officer at Genomics England, said: “Strategically, we’re at a point where genomic science is becoming an integral part of the national infrastructure in routine healthcare. This study illustrates the value of whole genome sequencing to detect rare and common variants that influence critical illness requiring intensive care. It represents a major leap forward in our understanding of how our genetic makeup influences severe illness with COVID-19.”
Lord Kamall, minister for innovation at the Department of Health and Social Care (DHSC), added: "Clinical research has been vital in our fight against COVID-19 and the UK’s innovation is enabling us to transform our health service and ensure the NHS is able to deliver world-class care.
“This research is an important step forward in better understanding how COVID-19 impacts certain people, allowing us to take the necessary action to protect the most vulnerable and save lives.”
Whole genome sequencing reveals host factors underlying critical COVID-19 *Nature* 7 March 2022; doi: 10.1038/s41586-022-04576-6
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