Media release

From: Springer Nature

Genomics: Genetic factors associated with predisposition for COVID-19 critical illness

More than 20 host genetic variants that predispose patients who are infected with SARS-CoV-2 to become critically ill are revealed in this week’s Nature. The findings may have direct implications for the development of new treatments and the future prioritization of therapy. 

Critical illness in COVID-19 is caused by inflammatory lung injury, which is mediated by the host’s immune system. Genetic factors are known to have a role, but researchers are only just beginning to understand the nature of the variants that are involved.

In this study, Kenneth Baillie and colleagues compared whole genome sequences of more than 7,000 patients who became critically ill with COVID-19 with those of more than 48,000 matched control individuals to identify 23 variants that predispose to life-threatening disease. Sixteen of these are newly discovered variants. They include variants within genes involved in interferon signalling, leukocyte differentiation and the production of mucin proteins, which are important factors in the regulation of the immune system and functioning of the lung. Some of the variants identified are suitable targets for drugs, raising the possibility of new therapies designed to target the genetic mechanisms that predispose to life-threatening disease.

The results are also broadly consistent with a multicomponent model of COVID-19, in which at least two distinct components can predispose to life-threatening illness: a failure to control viral replication and an enhanced tendency towards pulmonary inflammation and intravascular coagulation.