In a new study, researchers found why some people with COVID-19 develop severe disease.
The findings also may provide the first molecular explanation for why more men than women die from COVID-19.
The research was conducted by scientists at the National Institutes of Health and elsewhere.
The wide variation in the severity of disease caused by SARS-CoV-2, the virus behind COVID-19, has puzzled scientists and clinicians.
SARS-CoV-2 can cause anything from a symptom-free infection to death, with many different outcomes in between.
From February 2020, the researchers enrolled thousands of COVID-19 patients to find out whether a genetic factor drives these disparate clinical outcomes.
The team 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. Most of those patients were men.
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 common among a subgroup of people who suffer from life-threatening COVID-19 pneumonia.
These findings are the first published results from the COVID Human Genetic Effort, an international project spanning more than 50 genetic sequencing hubs and hundreds of hospitals.
One author of the study is Helen Su, M.D., Ph.D., a senior investigator at the National Institute of Allergy and Infectious Diseases.
The study is published in Science.
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