| When two brothers fell critically ill with Covid-19 around the same time in March, their doctors were baffled. Both had been young and healthy, but within days they were unable to breathe on their own and, tragically, one of them died. Two weeks later, a second pair of Covid-stricken brothers appeared in the Netherlands, and geneticists were called in to investigate. What they uncovered was a path leading from rare flaws in the brothers' DNA 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, Bloomberg's Jason Gale reports, is the lack of a substance called interferon, which helps orchestrate the body's defense against viral pathogens and can be infused to treat conditions such as hepatitis. Now, increasing evidence suggests that a significant minority of Covid-19 patients get very ill because of an impaired interferon response.  A health-care worker uses a nasal swab to test for Covid-19 Photographer: Joe Raedle/Getty Images A pair of studies published this week in the journal Science also indicate that insufficient interferon may lurk at a dangerous turning point in SARS-CoV-2 infections. One showed that patients with antibodies to the immune substance are at high risk of severe infections, while a second found DNA flaws in interferon-related genes in at least 10% of severe Covid patients, most of them men. The research may help explain why men are at higher risk of serious disease; it also suggests that raising interferon levels may help some patients. That's an especially welcome development because the substance appears most efficacious in the early stages of infection, when life-threatening respiratory failure could still be averted. Dozens of studies of interferon treatment are now recruiting Covid-19 patients. It also shows how researchers' close attention to the details of rare outlier cases can throw light on lethal conditions and pave a path to better understanding and treatment. "The rare diseases and the more common forms of the same disease may converge, and we can learn from each other," said Alexander Hoischen, head of the lab at Radboud University Medical Center in Nijmegen that analyzed the DNA of the two sets of brothers. "That's the hope."—John Lauerman | 
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