Human genes linked to life-threatening Covid-19
Large-scale study of patient data highlights 49 genetic differences associated with critical illness.
Dozens of differences in people’s genomes, or genetic variants, have been discovered between those who become critically ill with Covid-19 infection and those who do not.
Many of these genetic variants, found in a study of seriously ill patients, are linked to patients’ immune response and their effects may be treatable by repurposing existing drugs.
For the first time, the study also showed the link between genetic variants related to the SARS-CoV-2 virus entering the cells and severe Covid-19 disease.
The outcomes are from a worldwide collaboration of scientists and doctors seeking to understand and manage critical illness by examining how patients’ genes affect their predisposition to disease.
Their study is helping to explain why some people have no symptoms from Covid-19, while others become critically ill, or die.
Their discovery underscores the value of studying genetics in large groups of people to reveal key processes behind disease.
The Genetics of Mortality in Critical Care (GenOMICC) team, led by a researcher from the Roslin Institute, studied DNA recovered from patients who had received critical care for Covid-19, and data from other studies involving patients with severe and critical Covid-19.
From their analysis, they were able to infer how the findings translate into gene activity and production of proteins in the body.
This enabled the team to identify genetic variants linked to the immune system and genetic variants that impact on how virus takes hold and replicates in the body.
To date, scientists have identified 49 genetic variants associated with critical illness with Covid-19, including 16 uncovered in their latest study.
The latest finding builds on previous work in which the team used genetics to discover the potential of a specific treatment, called baricitinib, to treat severe Covid-19. This was the first evidence in critical illness and infectious disease for finding an effective drug using human genetics.
Together, findings from the study deepen scientists’ understanding of critical Covid-19 and highlight new mechanisms of disease, several of which have the potential to lead to new, effective treatments.
The study was published in Nature.
GenOMICC is funded by the charity Sepsis Research (FEAT), the Intensive Care Society, Wellcome, UKRI and Scotland’s Chief Scientist Office.
Our latest findings significantly expand our understanding of how genetic differences between people lead to differences in their risk of developing life-threatening illness in Covid-19. Most importantly, these results point us at already available drugs which could be repurposed to treat severe Covid-19. More broadly, our work on Covid-19 has demonstrated the potential for genetics to play an important role in successfully tackling many other conditions, like sepsis or flu, that we encounter in critical care during normal times.
** 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. **
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