When two brothers fell critically ill with COVID-19 around the same time in March, their doctors were baffled. Both were young — 29 and 31 years old — and healthy. Yet within days they couldn’t breathe on their own and, tragically, one of them died.

Two weeks later, when a second pair of COVID-19-stricken brothers, both in their 20s, also appeared in the Netherlands, geneticists were called in to investigate. What they uncovered was a path leading from severe cases, genetic variations and gender differences to a loss of immune function that may ultimately yield a new approach to treating thousands of coronavirus patients.

The common thread in the research is the lack of a substance called interferon that helps orchestrate the body’s defense against viral pathogens and can be infused to treat conditions such as infectious hepatitis. Now, increasing evidence suggests that a significant minority of COVID-19 patients get very ill because of an impaired interferon response. Twin landmark studies published Thursday in the journal Science showed that insufficient interferon may lurk at a dangerous turning point in SARS-CoV-2 infections.