The secret why some people don’t get Covid

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

In the early days of the pandemic, a small, tight-knit community of scientists from around the world formed an international consortium called COVID Human Genetic Effort, whose goal was to search for a genetic explanation for why some people became seriously ill with Covid , while others got away with a slight sniffle.

After a while, the group noticed that some people didn’t get infected at all – despite repeated and intense exposure. The most intriguing cases were the partners of people who got really sick and ended up in intensive care. “We’ve heard from some spouses of these people who don’t appear to have contracted the disease despite caring for their husband or wife without access to face masks,” says András Spaan, a clinical microbiologist at Rockefeller University in New York.

Spaan was hired to set up part of the project to study these apparently immune individuals. But they had to find a good number of them first. So the team put out a paper nature immunology in which they outlined their intention, with a subtle last line mentioning that “subjects from all over the world are welcome”.

The response, says Spaan, was overwhelming. “We literally got thousands of emails,” he says. The sheer volume rushing to sign up forced them to set up a multilingual online screening survey. To date, around 15,000 applications have been received from all over the world.

The theory that these people may 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 should Covid be any different, streamlined team? However, in the long history of immunology, the concept of innate resistance to infection is fairly new and esoteric. Few scientists are even interested in it. “It’s such a niche area that even in the medical and research fields it’s a bit frowned upon,” says Donald Vinh, associate professor in the Department of Medicine at McGill University in Canada. Geneticists don’t recognize it as proper genetics, nor does immunologists recognize it as proper immunology, he says. And this despite the fact that there is a clear therapeutic goal. “If you can figure out why someone can’t get infected, then you can figure out how to prevent people from getting infected,” says Vinh.

But it’s getting harder and harder to find immune people. While many have volunteered, only a small minority meet the narrow criteria of likely having been in contact with the virus but not having antibodies to it (which would indicate infection). The most promising candidates are those who have defied all logic not to catch Covid despite being at high risk: healthcare workers who are constantly exposed to Covid-positive patients, or those who lived with confirmed people – or still do better to be infected shared a bed with them.

As the team began searching for suitable people, it also worked against mass vaccination programs. “On the one hand, a lot of people got vaccinated, which is great, don’t get me wrong,” says Vinh. “But these aren’t the people we want.” On the other hand, finding the unvaccinated invites “a bit of a marginalized population.” Of the thousands who poured in after the call, about 800 to 1,000 recruits fit that tight bill.

Then came the highly infectious Omicron variant. “Omicron really ruined this project, I have to be honest with you,” says Vinh. It dramatically reduced their candidate pool. But Spaan sees Omicron’s defilement in a more positive light: That some recruits survived the Omicron waves really supports the existence of innate resistance.

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