We all know a “Covid virgin” or “Novid”, someone who defied logic by dodging the coronavirus. But beyond judicious caution, pure chance or a lack of friends, could the secret of these people’s immunity lie in their genes? And could he hold the key to fighting the virus?
At the start of the pandemic, a small, tight-knit community of scientists around the world created an international consortium, called the COVID Human Genetic Effort, whose aim was to seek a genetic explanation for why some people were becoming seriously ill with Covid while in others got away with a mild case of sniffling.
After a while, the group noticed that some people were not infected at all, despite repeated and intense exposures. The most intriguing cases were the partners of people who got really sick and ended up in intensive care. “We have heard of a few spouses of these people who, despite taking care of their husband or wife, without having access to face masks, apparently did not contract an infection,” explains András Spaan, clinical microbiologist at Rockefeller University in New York.
Spaan was tasked with setting up a branch of the project to investigate these apparently immune individuals. But first they had to find a good number of them. The team therefore published an article in Natural immunology in which they described their company, with a discreet last line mentioning that “subjects from all over the world are welcome”.
The response, says Spaan, has been overwhelming. “We literally received thousands of emails,” he says. The huge volume of applications for registration forced them to set up a multilingual online pre-screening survey. So far, they have received around 15,000 applications from all over the world.
The theory that these people might have pre-existing immunity is supported by historical examples. There are genetic mutations that confer natural immunity to HIV, norovirus and a parasite that causes recurrent malaria. Why would Covid be any different, the team rationalized? Yet, in the long history of immunology, the concept of innate resistance against infection is quite new and esoteric. Only a few scientists are interested in it. “It’s such a niche area that even in the fields of medicine and research, it’s a bit of a poo,” says Donald Vinh, an associate professor in the Department of Medicine at McGill University in Canada. Geneticists don’t recognize it as good genetics, nor immunologists as good immunology, he says. This despite a clear therapeutic objective. “If you can figure out why someone can’t get infected, well, you can figure out how to prevent people from getting infected,” Vinh says.
But finding immune people is an increasingly tricky task. While many have volunteered, only a small minority meet the narrow criteria of likely having encountered the virus without having antibodies against it (which would indicate infection). The most promising candidates are those who have defied logic by not catching Covid despite their high risk: carers constantly exposed to Covid-positive patients, or those who have lived with – or better yet, shared a bed with – people confirmed to be infected.
When the team started looking for suitable people, they were also working against mass vaccination programs. “On the one hand, a lot of people were getting vaccinated, which is great, don’t get me wrong,” Vinh says. “But these are not the people we want.” On the other hand, searching for the unvaccinated “kinda invites a marginal population.” Of the thousands that poured in after the roll call, around 800 to 1,000 recruits fit that tight budget.
Then came the highly contagious variant of Omicron. “Omicron really ruined this project, I have to be honest with you,” Vinh says. This significantly reduced their pool of candidates. But Spaan sees the desecration of Omicron in a more positive light: the fact that some recruits have survived the waves of Omicron really supports the existence of an innate resistance.
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