Study: Genetic variants linked to severe COVID-19

PARIS — Scientists said Friday they had identified genetic variants that made patients more likely to develop severe COVID-19, in a breakthrough that could see new and existing drugs help patients survive the illness.

To determine why some people develop severe lung inflammation when sick with COVID-19, researchers analyzed mutations on the genomes of more than 2,000 critically ill patients across Britain.

They compared their genetic make-up to that of a control group and identified as many as eight sequences that were more common among the COVID-19 patients.

They found that these sequences are involved in the body’s inflammatory response and how the immune system battles pathogens such as the novel coronavirus.

After further computer analysis, they highlighted two specific genes — TYK2 and CCR2 — that encode inflammatory protein molecules.

The researchers found that individuals who produce more of the TYK2 enzyme appeared to be at higher risk of developing severe COVID-19.

“We’re trying to cut through the tremendous complexity of the human immune system to find the levers that we can pull that will change the outcome for the patient,” said Kenneth Baillie, a geneticist at the University of Edinburgh and lead author of the study published in Nature.

“The beauty of genetics is that it can predict the effects that a drug might have. The really exciting thing about this study is that we have found genes that are directly therapeutically relevant, so they lead us directly to treatment.”

Baillie said that there is already a group of drugs on the market that limits the action of TYK2. These are known as JAK inhibitors and are often prescribed for chronic diseases such as cancer and arthritis.

“We showed that people who produce more TYK2 are more at risk of Covid. And there’s a drug that inhibits it,” he told journalists via video-link.

The authors noted that there was also an antibody treatment currently in clinical trials that blocks CCR2, a protein involved in the immune response.

They said wide-scale trials were urgently needed to test these treatments on patients with severe COVID-19.

Sir Mark Caulfield, chief scientist for Genomics England and director of the NIHR Biomedical Research Centre at Barts Hospital, called Friday’s research “a remarkable result.”

He said the team’s study of patient genomes could eventually create a “comprehensive inventory of variants that change our susceptibility to the severity of COVID.”

“And maybe, just maybe, as a result, we will find a new therapy that will help people survive this better.”