Gene variants linked to severe cases of Covid-19
Genes with links to critical illness offer routes to investigate novel treatments.
Fresh details of some biological mechanisms behind severe Covid-19 have been revealed in the world’s largest study of the genetics of the disease, involving more than 57,000 people.
Some 16 new variations of genes associated with severe Covid-19, including some related to blood clotting, immune response and intensity of inflammation, have been identified in the study, led by a Roslin scientist.
These findings will act as a roadmap for future efforts, opening avenues of research focused on potential new therapies and diagnostics with pinpoint accuracy, experts say.
Researchers from the GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) consortium – a global collaboration to study genetics in critical illness – led by the University of Edinburgh in partnership with Genomics England, made these discoveries by determining the genetic codes of 7,491 patients from 224 intensive care units in the UK.
The patients’ DNA was compared with that of 48,400 other people who had not had Covid-19, who are participants in Genomics England's 100,000 Genomes Project, and that of a further 1,630 people who had experienced mild Covid-19.
Determining the whole genome sequence for all participants in the study allowed the team to create a precise map and identify genetic variation linked to severity of Covid-19.
The team found key differences in 16 genes in the ICU patients when compared with the DNA of the other groups.
They also confirmed the involvement of seven other genetic variations already associated with severe Covid-19, discovered in earlier studies from the same team.
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.
The findings included how a single gene variant that disrupts a key messenger molecule in immune system signalling – called interferon alpha-10 – was enough to increase a patient’s risk of severe disease.
This highlights the gene’s key role in the immune system and suggests that treating patients with interferon – proteins released by immune cells to defend against viruses – may help manage disease in the early stages.
Variations in genes that control the levels of a central component of blood clotting – known as Factor 8 – are associated with critical illness in Covid-19, the study, published in Nature, found.
This may explain some of the clotting abnormalities that are seen in severe cases of Covid-19. Factor 8 is the gene underlying the most common type of haemophilia.
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.
GenOMICC is funded by the UK Department of Health and Social Care, LifeArc, the charity Sepsis Research FEAT, the Intensive Care Society, Wellcome, UK Research and Innovation, Scotland’s Chief Scientist Office, the Department of Health and Social Care and the National Institute for Health Research (NIHR), and supported by Illumina.
** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **