Scientists Identify Genetic Factors That May Explain Severe Covid-19 Cases

Scientists Identify Genetic Factors That May Explain Severe Covid-19 Cases Misguided antibodies may be partially to blame Alexandra Sifferlin Medium

Reserchers at multiple labs, including at the National Institutes of Health (NIH), have published two papers today in the journal Science that may help explain one of the greater mysteries of the Covid-19 pandemic: why some people develop severe forms of the disease while other people have mild cases.

It turns out a significant portion of people who develop severe symptoms have “misguided” antibodies that attack a person’s immune system instead of the virus. Among the people studied, this abnormal immune response occurred much more often in men (which might offer some explanation as to why more men than women die from Covid-19).

The findings are some of the first results published by the COVID Human Genetic Effort, a global collaborative project that aims to understand whether there are genetic or immunologic differences that might play into a person’s disease severity or resistance to the virus. Researchers have enrolled thousands of people with Covid-19 into studies to try to understand potential genetic factors that affect how a Covid-19 infection plays out.

The NIH distilled the findings as such:

The researchers found that more than 10% of people who develop severe Covid-19 have misguided antibodies—autoantibodies—that attack the immune system rather than the virus that causes the disease. Another 3.5% or more of people who develop severe Covid-19 carry a specific kind of genetic mutation that impacts immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies or—because of a faulty gene—were produced in insufficient amounts or induced an inadequate antiviral response, their absence appears to be a commonality among a subgroup of people who suffer from life-threatening Covid-19 pneumonia.

Taken together, the findings suggest that among a (small) group of people with serious Covid-19 infections, the body’s interferon response appears to be malfunctioning either due to genetic issues or wayward antibodies. The discovery could affect the way people with Covid-19 are treated. As journalist Meredith Wadman reports for Science, synthetic interferons — which are under investigation to treat SARS-CoV-2 — and therapies aimed at removing damaging antibodies might be useful. ...