More recently, Casanova and his teammates tried to get a sense of the scope of immune deficiencies in relatively young people who get very ill with COVID. In a paper published in August, they offered evidence suggesting that about 1 percent of men under 60 years old who developed life-threatening COVID have a mutation on the X chromosome that affects a receptor known as TLR7, which sits on the surface of immune cells and carries signals about microbe invaders. The scientists found this mutation in 16 of the more than 1,200 people with unexplained critical COVID in the study, but it was totally absent in more than 300 people ​​who either had mild illness or were asymptomatic. The connection between TLR7 and severe COVID has been found by other groups as well. “Given that there have been many studies demonstrating the impact of TLR7 variants on COVID-19 severity, we believe this is likely a true signal,” says Tomoko Nakanishi, a respirologist at McGill University, in Montreal, who was in one such group.

An international collaboration has also uncovered genetic variants associated with severe illness from the coronavirus. Some are thought to diminish levels of an enzyme called oligoadenylate synthase, which normally helps chew up viruses. A paper published in just the past few days joined others in finding that a variant affecting one form of that enzyme is also associated with worse COVID outcomes; its authors note that this variant is common in all people, although less so among those with African ancestry. Yet another common variant—this one found in as many as 15 percent of individuals of European descent—could increase the risk of severe COVID by 70 percent, and by 170 percent in people less than 60 years old, according to a paper this month from Nakanishi and colleagues.