Scientists pinpoint genes common among people with severe coronavirus infections

Certain gene variants are linked to severe coronavirus infections, according to a team of scientists in Europe who studied the genomes of 2,200 critically ill COVID-19 patients. Their results provide robust support that genetic makeup plays a role in the potentially fatal illness experienced by some people infected by the coronavirus.

Diving into people’s DNA is an approach that could help answer one of the pandemic’s biggest mysteries: Why do some people have mild coronavirus cases, or no symptoms at all, while others rapidly fall ill and die? Evidence is clear that older age and underlying conditions are risk factors for increased COVID-19 severity. But genetic predispositions to runaway inflammation or other harmful immune responses could also contribute to worse disease.

Knowing this, researchers are working to uncover genes closely linked with biological systems to accelerate drug development for COVID-19.

“Our primary aim in this work is to find effective treatments,” said study author Kenneth Baillie, a University of Edinburgh clinical researcher and an investigator with the GenOMICC Consortium, which explores associations between genes and critical illness.

Baillie and his colleagues pinpointed eight spots on chromosomes — five of which strongly held up under further scrutiny — where variants were more common among people in intensive care. Some of the genes contain instructions for anti-viral components of the immune system, suggesting flaws in a person’s microscopic defenses that therapeutics might fix, at least in theory.

In what’s known as a genome-wide association study, Baillie and his colleagues examined the genes of more than 2,000 COVID-19 patients in intensive care units across Britain, and compared those with the genes of healthy people. The research, published recently in the journal Nature, aligns with earlier reports that also found variants in the genetic makeup of critically ill patients.

The new report is the “biggest published to date of its kind,” said Tom Hemming Karlsen, a physician at the University of Oslo who did not participate in the new work. He is a coauthor of a paper, published earlier this year in the New England Journal of Medicine, which used the same scientific process to identify gene variants associated with severe COVID-19.

That study found people with blood type A were at higher risk of severe infections, while having blood type O was somewhat associated with a protective effect. It also noted a location on chromosome 3 linked to respiratory failure.

The study reveals that “genetic variants, particularly near genes that are involved in the so-called interferon immune response play an important role in causing a life-threatening COVID-19 infection,” said Lude Franke, a statistical geneticist at the University of Groningen, who was not involved in the Nature report.

Experts cautioned these types of investigations rarely produce evidence for direct cause-and-effect relationships between specific genes and disease severity or susceptibility to infection.

“A chunk of the answer is in our genes” but “it’s unlikely that a single element is fully responsible for the development of severe COVID-19,” study author Sara Clohisey, a researcher at the University of Edinburgh, pointed out.

Interferon has been tested as a possible COVID-19 therapy in clinical trials, although one large trial found giving interferon to hospitalized patients did not reduce mortality.