A full analogue to the HIV, malaria, and norovirus stories may not be possible. Genuine resistance can manifest in only so many ways, and tends to be born out of mutations that block a pathogen’s ability to force its way inside a cell, or xerox itself once it’s inside. CCR5, Duffy, and the sugars dropped by FUT2, for instance, all act as microbial landing pads; mutations rob the bugs of those perches. If an equivalent mutation exists to counteract SARS-CoV-2, it might logically be found in, say, ACE2, the receptor that the coronavirus needs in order to break into cells, or TMPRSS2, a scissors-like protein that, for at least some variants, speeds the invasive process along. Already, researchers have found that certain genetic variations can dial down ACE2’s presence on cells, or pump out junkier versions of TMPRSS2—hints that there could be tweaks that further strip away the molecules. But “ACE2 is very important” to blood-pressure regulation and the maintenance of lung-tissue health, said Su, of NIAID, who’s one of many scientists collaborating with Casanova to find SARS-CoV-2 resistance genes. A mutation that keeps the coronavirus out might very well “muck around with other aspects of a person’s physiology.” That could make the genetic tweak vanishingly rare, debilitating, or even, as Gupta put it, “not compatible with life.” People with the CCR5-Δ32 mutation, which halts HIV, “are basically completely normal,” Cannon told me, which means “HIV kind of messed up in ‘choosing’ CCR5.” The coronavirus, by contrast, has figured out how to exploit something vital to its host—an ingenious invasive move.

The superpowers of genetic resistance can have other forms of kryptonite. A few strains of HIV have figured out a way to skirt around CCR5, and glom on to another molecule, called CXCR4; against this version of the virus, even people with the Δ32 mutation are not safe. A similar situation has arisen with Plasmodium vivax, which “we do see in some Duffy-negative individuals,” suggesting that the parasite has found a back door, says Dyann Wirth, a malaria researcher at Harvard’s School of Public Health. Evolution is a powerful strategy—and with SARS-CoV-2 spewing out variants at such a blistering clip, “I wouldn’t necessarily expect resistance to be a checkmate move,” Cannon told me. BA.1, for instance, conjured mutations that made it less dependent on TMPRSS2 than Delta was.