Abstract

From the first months of the COVID-19 pandemic, scientists baffled by the disease's ferocity have wondered whether the body's vanguard virus fighter, a molecular messenger called type I interferon, is missing in action in some severe cases. Two papers published online in Science this week confirm that suspicion. They reveal that in a significant minority—14%—of a large global sample of patients hospitalized with life-threatening COVID-19, the body's interferon response has been crippled by genetic flaws or by rogue antibodies that attack interferon itself. And nearly all of the people with the destructive antibodies, who accounted for 10% of all gravely ill patients, were male. "There has never been any infectious disease explained at this level by a factor in the human body," says Isabelle Meyts, a pediatric immunologist at the University Hospitals Leuven, who was a co-author on both studies. The findings have immediate practical implications, from screening to pick out at-risk patients to possible treatments for them. And the researchers, led by Jean-Laurent Casanova of Rockefeller University, caution that going forward, plasma donations from recovered patients should be screened to ensure that they don't contain the destructive antibodies.