Scientists find two root causes of severe COVID-19

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People infected by the novel coronavirus can have symptoms that range from mild to deadly.

In two new studies, researchers found that some life-threatening cases can be traced to weak spots in patients’ immune systems.

They found at least 3.5% of study patients with severe COVID-19, the disease caused by the novel coronavirus, have mutations in genes involved in antiviral defense.

And at least 10% of patients with severe disease create “auto-antibodies” that attack the immune system, instead of fighting the virus.

The results identify some root causes of life-threatening COVID-19.

They also provide an explanation for why COVID-19 can be so severe in some people, while most others infected by the same virus are okay.

The research was conducted by a team at Rockefeller University.

The team first began enrolling COVID-19 patients in their study in February.

At the time, they were seeking young people with severe forms of the disease to test whether these patients might have underlying weaknesses in their immune systems that made them especially vulnerable to the virus.

In March, the team was aiming to enroll 500 patients with severe COVID-19 worldwide in their study. By August, they had more than 1,500, and they now have over 3,000.

As the researchers began analyzing patient samples, they started to uncover harmful mutations, in people young and old.

The team found that 23 out of 659 patients studied carried errors in genes involved in producing antiviral interferons.

Without a full complement of these antiviral defenders, COVID-19 patients wouldn’t be able to fend off the virus, the researchers suspected.

The team’s analysis of 987 patients with life-threatening COVID-19 revealed just that.

At least 101 of the patients had autoantibodies against an assortment of interferon proteins.

These antibodies blocked interferon action and were not present in patients with mild COVID-19 cases.

The vast majority—94%—of patients with the harmful antibodies were men. Men are more likely to develop severe forms of COVID-19, and this work offers one explanation for gender variability.

The team says the work could change how doctors and health officials think about vaccination distribution strategies and even potential treatments.

In addition to the current work, the team and hundreds of other scientists involved with an international consortium called the COVID Human Genetic Effort are working to understand a second piece of the coronavirus puzzle.

Instead of hunting for factors that make patients especially vulnerable to COVID-19, they’re looking for the opposite—genetic factors that might be protective.

One author of the study is Jean-Laurent Casanova, a Howard Hughes Medical Institute Investigator at The Rockefeller University.

The study findings are published in Science and Science.

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