Genetic study gives insights into severe COVID-19
The world’s largest study of the genetics of critical COVID-19 has revealed fresh details about some of the biological mechanisms behind the severe form of the disease.
Researchers made the discoveries by sequencing the genomes of patients from intensive care units in the UK, including University Hospital Southampton (UHS).
Some 16 new genetic variants associated with severe COVID-19 have been identified. These include some related to blood clotting, immune response and intensity of inflammation.
These findings will act as a roadmap for future efforts. Experts say they will open new fields of research focused on potential new therapies and diagnostics with pinpoint accuracy.
Studying severe illness
GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) is led by the University of Edinburgh. Since 2020 is has focussed on COVID-19 research with several partners including Genomics England.
Dr Rebecca Cusack, UHS consultant anaesthetist and Southampton lead for the study, explained: “Examining the DNA sequences of people who have suffered a critical illness enables us to gain insights as to what makes us susceptible to severe illnesses.
“Recently this study led to significant breakthroughs in the understanding of genetic variations linked to severe COVID-19. This has identified potential treatments which may ultimately save lives.
“More than 120 critically ill patients in Southampton have donated blood and saliva samples to advance the research into these lifesaving treatments. Thank you to you all. Your generosity has contributed to advancement of medical science during the unprecedented crisis of the COVID-19 pandemic.”
Whole genome sequencing
Researchers sequenced 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.
Determining the whole genome sequence for all participants allowed the team to identify genetic variation linked to severity of COVID-19. They 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.
The findings have been published in Nature.
Interferon insight
A single gene variant was found to disrupt a molecule in immune system signalling called interferon alpha-10. This increased a patient’s risk of severe disease.
It suggests that treating patients with interferon may help manage disease in the early stages.
The study also found that variations in genes that control the levels of a central component of blood clotting – known as Factor 8 – were associated with critical illness in COVID-19.
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.