We all know a “Covid virgin,” or “Novid,” someone who has defied all logic in dodging the coronavirus. But beyond judicious caution, sheer luck, or a lack of friends, could the secret to these people’s immunity be found nestled in their genes? And could it hold the key to fighting the virus? 

In the early days of the pandemic, a small, tight-knit community of scientists from around the world set up an international consortium, called the COVID Human Genetic Effort, whose goal was to search for a genetic explanation as to why some people were becoming severely sick with Covid while others got off with a mild case of the sniffles. 

After a while, the group noticed that some people weren’t getting infected at all—despite repeated and intense exposures. The most intriguing cases were the partners of people who became really ill and ended up in intensive care. “We learned about a few spouses of those people that—despite taking care of their husband or wife, without having access to face masks—apparently did not contract infection,” says András Spaan, a clinical microbiologist at Rockefeller University in New York. 

Spaan was tasked with setting up an arm of the project to investigate these seemingly immune individuals. But they had to find a good number of them first. So the team put out a paper in Nature Immunology in which they outlined their endeavor, with a discreet final line mentioning that “subjects from all over the world are welcome.” 

The response, Spaan says, was overwhelming. “We literally received thousands of emails,” he says. The sheer volume rushing to sign up forced them to set up a multilingual online screening survey. So far, they’ve had about 15,000 applications from all over the world. 

The theory that these people might have preexisting immunity is supported by historical examples. There are genetic mutations that confer natural immunity to HIV, norovirus, and a parasite that causes recurring malaria. Why would Covid be any different, the team rationalized? Yet in the long history of immunology, the concept of inborn resistance against infection is a fairly new and esoteric one. Only a few scientists even take an interest. “It’s such a niche field, that even within the medical and research fields, it’s a bit pooh-poohed on,” says Donald Vinh, an associate professor in the Department of Medicine at McGill University in Canada. Geneticists don’t recognize it as proper genetics, nor immunologists as proper immunology, he says. This is despite there being a clear therapeutic goal. “If you can figure out why somebody cannot get infected, well, then you can figure out how to prevent people from getting infected,” says Vinh. 

But finding immune people is an increasingly tricky task. While many have volunteered, only a small minority fit the narrow criteria of probably having encountered the virus yet having no antibodies against it (which would indicate an infection). The most promising candidates are those who have defied all logic in not catching Covid despite being at high risk: health care workers constantly exposed to Covid-positive patients, or those who lived with—or even better, shared a bed with—people confirmed to be infected. 

By the time the team started looking for suitable people, they were working against mass vaccination programs too. “On the one hand, a lot of people were getting vaccinated, which is great, don’t get me wrong,” says Vinh. “But those are not the people we want.” On the other hand, seeking out the unvaccinated “does invite a bit of a fringe population.” Of the thousands that flooded in after the call, about 800 to 1,000 recruits fit that tight bill.

Then the highly infectious Omicron variant arrived. “Omicron has really ruined this project, I have to be honest with you,” says Vinh. It dramatically reduced their pool of candidates. But Spaan views Omicron’s desecration in a more positive light: that some recruits survived the Omicron waves really lends support to the existence of innate resistance.