Faulty gene and an autoimmune condition linked to severe COVID-19

The way that SARS-CoV-2 can cause a quiet, symptom-free infection in some people, or kill some others in a matter of days has left many puzzling. However, compelling evidence now suggests that more severe susceptibility to the virus may be due to single-gene mutations that affect an individual’s immune response – research shows that more than 10% of young and healthy people who develop severe COVID-19 have misguided antibodies that attack not the virus, but the immune system itself, while another 3.5% carry a specific faulty gene that is otherwise crucial to protecting the body from viruses.

The research findings help explain why some people develop a disease much more severe than others in their age group—including those who require admission to intensive care despite being in their 20s and free of underlying conditions. They may also provide the first molecular explanation for why more men than women die from the disease.

According to Jean-Laurent Casanova, Head, St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University, US, the cause of life-threatening COVID-19 is likely due to lack of type I interferons, which is a set of 17 proteins. Interferons are part of the intrinsic immunity, immediately heightening cells’ defenses in response to viruses before the adaptive immune system mounts an antibody response.

Experiments on roughly 11,000 patients with severe disease showed that their immune cells did not produce any detectable type I interferons in response to SARS-CoV-2. Another experiment showed that auto-antibodies against interferons can also effectively curb their activity and affect disease severity. The majority of patients who were confirmed to have these auto-antibodies were men.

“[…] the auto-antibodies are actually the underlying reason some people get very sick, and not the consequence of the infection,” Casanova observed. His team will look at two types of interferons already available as drugs to find suitable use for COVID-19.

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