Perhaps the most unnerving aspect of COVID-19 is its startling range of severity: from completely asymptomatic to deadly. Starting early in the pandemic, researchers identified factors that put people at risk of a serious case of the disease, such as advanced age, having certain chronic diseases and being male. But these demographic trends do not get at the biological mechanisms that actually cause a life-threatening infection. Nor do they explain why some young, fit, healthy people become mortally ill from the SARS-CoV-2 virus.

Two related papers published in Science onSeptember 24 begin to address these mysteries. They may also partially account for men’s greater vulnerability to the virus and point the way to possible treatments and protective measures. Both studies highlight the critical role of a class of immune system proteins called interferons, so named because they interfere with the replication of viruses.

The new papers were produced by the