The genome-wide association study was conducted by members of the global GenOMICC consortium – led by researchers at the University of Edinburgh in collaboration with Genomics England – and published in the journal Nature. It represents the largest study on the genetics behind critical care in COVID-19 yet and identified 16 important genetic variants that increase the risk of developing life-threatening symptoms.
'These results explain why some people develop life-threatening COVID-19, while others get no symptoms at all' said Professor Kenneth Baillie, the lead investigator for the study. '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.'
Researchers fully sequenced the genomes of 7491 patients from 224 intensive care units. This data was compared with the genomes of 48,400 people who had not had COVID-19 and 1630 patients with mild symptoms. From this comparison, the researchers were then able to create a map of the patient's genomes and identify differences in 16 genes that were linked to the intensive care patients.
Seven of the variations were in genes previously highlighted by the group (see BioNews 1076). However, variations in new key genes for multiple components of the immune response were also identified, such as the genes Il10RB and PLSCR1 that are involved in signalling between immune cells.
Variations in the genes F8 and PDGFRL, which are key regulators of blood clotting, were also discovered. This is particularly significant, as abnormalities in clotting have been observed in severe COVID-19 cases.
'As COVID-19 evolves, we need to focus on reducing the number of people getting seriously ill and being hospitalised' said Professor Sir Mark Caulfield, a co-author on the study. '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.'
Ascertaining the genetic factors that contribute to the severity of COVID-19 symptoms is a highly active field of research (see BioNews 1129 and 1103). Previously, there have been concerns that ethnicity could be being overlooked in such studies (see BioNews 1063).
Dr Richard Scott, chief medical officer for Genomics England, added that the group 'went to great efforts to engage with all communities within the UK – including groups that have been historically under-represented in medical studies. The inclusive element of our work has generated meaningful results for everyone in the country.'