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Scientists have identified mutations in five genes associated with the development of life-threatening diseases in Covid-19 patients.
The researchers say that knowing which genes are involved in severe cases of coronavirus could help them identify existing drugs that could help treat the disease.
Dr Kenneth Baillie, the project’s principal investigator and principal investigator at the Roslin Institute at the University of Edinburgh, said: “This is an amazing realization of the promise of human genetics to help understand critical illness.
‘As in sepsis and influenza, in Covid-19, the damage to the lungs is caused by our own immune system, rather than the virus itself.
“Our genetic results provide a roadmap through the complexity of immune signals, showing the route to key drug targets.
“Our results immediately highlight which drugs should be at the top of the list for clinical trials.
“We can only test a few drugs at a time, so making the right decisions will save thousands of lives.”
Dr Baillie and his team conducted a genome-wide association study (GWAS) on 2,244 critically ill Covid-19 patients from 208 intensive care units (ICUs) in the UK.
GWAS is a commonly used study design that allows scientists to identify which genes are involved in human disease.
Working with experts from the GenOMICC consortium, a global collaboration investigating links between genetics and critical illness, the researchers compared the genetic information of Covid-19 patients in ICU with samples provided by healthy volunteers from other studies.
The team, whose work was published in the journal Nature, found that variations in five genes, IFNAR2, TYK2, OAS1, DPP9, and CCR2, were associated with the development of severe disease in Covid-19 patients.
The scientists said they were able to identify two molecular processes – antiviral immunity and lung inflammation) associated with the genes.
Innate antiviral defenses are known to be important early in the disease, while inflammatory processes triggered by infection are a key feature of severe infection, the researchers said.
However, the team said the research was not aimed at predicting who is likely to become seriously ill with Covid-19, but is more focused on finding “biological clues that will lead us to effective treatments.”
This is because some patients with particular genetic variants may respond to certain drugs, and researchers believe that genetic evidence could be used to indicate which treatments will be effective in a disease.
For example, they said, drugs that reduce the activity of the TYK2 gene could also help protect against Covid-19.
A class of anti-inflammatory drugs called JAK inhibitors, which includes the drug baricitinib, produces this effect, they added.
The researchers also said that the risk ratio (the overall probability of becoming critically ill with Covid-19) associated with genetic variants is estimated to be around 6.5%.
They said this is much lower compared to other known risk factors for Covid-19, such as age and underlying health conditions.
The team said that additional clinical trials should focus on drugs that target specific antiviral and anti-inflammatory pathways.
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