Five Genes Associated with COVID-19 Severity Identified

A genome-wide association study in over 2,200 critically ill COVID-19 patients identified five genes that were associated with the most severe cases of the disease. 

The researchers from the University of Edinburgh, whose findings was published in Nature today, found key differences in five genes of the ICU patients compared with samples provided by healthy volunteers. The genes—IFNAR2, TYK2, OAS1, DPP9 and CCR2—partially explain why some people become desperately sick with COVID-19, while others are not affected.

Having highlighted the genes, the team were then able to predict the effect of drug treatments on patients, because some genetic variants respond in a similar way to particular drugs. They showed that a reduction in the activity of the TYK2 gene protects against COVID-19. A class of anti-inflammatory drugs called JAK inhibitors, which includes the drug baricitinib, produces this effect.

They also discovered that a boost in the activity of the gene INFAR2 is also likely to create protection, because it is likely to mimic the effect of treatment with interferon. However, experts caution that to be effective, patients might need the treatment early in disease.

The project’s chief investigator Kenneth Baillie said, "This is a stunning realization of the promise of human genetics to help understand critical illness. Just like in sepsis and influenza, in COVID-19, 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.