Why do some patients develop particularly severe SARS-CoV-2 infection while others do not? A new study from the COVID Human Genetic Effort, a consortium of research centers in 40 countries, suggests that previously unidentified autoimmune factors may be the reason some patients with no known risks develop life-threatening cases of COVID-19.

Older age, male sex, and the presence of underlying medical problems increase an individual's risk of severe COVID-19 infection; obesity increases the risk of death from COVID-19. But these factors don't explain why many apparently healthy (and sometimes younger) people end up in ICUs with serious COVID-19 infections.

Now researchers have identified autoantibodies that disable key interferons in some patients with COVID-19. Interferons are proteins in the immune system that help patients mount a rapid response to viruses. They "sound the alarm" that alerts other parts of the immune system to invaders while also acting directly against the virus. Only some types of interferons are affected by autoantibodies, but researchers say the damage seems to be sufficient to "tip the balance in favor of the virus . . . [resulting in] devastating disease."

However, autoantibodies are not found in all patients with severe COVID-19. Autoantibodies against at least one type of interferon were found in 101 of 987 patients who were battling life-threatening COVID-19 pneumonia. They were also identified in four of 1,227 healthy controls whose plasma samples were collected prior to the pandemic. No autoantibodies were found in 663 people experiencing mild or asymptomatic COVID-19 infection.

Individuals with autoantibodies ranged in age from 25 to 87 years, and 94% were men. The presence of autoantibodies in both men and women was associated with worse outcomes; 36.6% died from the infection. This contrasts with U.S. mortality rates ranging generally from 0.01% at 25 years to 15% at 85 years.

The findings offer additional insight into the pathophysiology of severe COVID-19 disease, but they don't point to specific COVID-19 preventive measures or new treatments. The researchers recommend that patients who have recovered from COVID-19 be tested for autoantibodies before donating convalescent plasma.-Betsy Todd, MPH, RN