Yes, they exist, says immunologist Isabelle Meyts (UZ Leuven), people who are naturally resistant to infection with the sars-CoV-2 virus, which causes Covid-19. Put them in an intensive care unit full of severely ill covid patients for a week without vaccination and without protective clothing, and the virus will not hurt them. “They have an innate genetic resistance to the virus. We hope to learn what mechanisms help them stay out of the grip of the virus.”
Meyts is part of an international group of scientists that is hunting for these ‘natural resistors’. Filomeen Haerynck, an immunologist at UZ Gent, is also involved in the project. “It will be quite a journey to find these exceptional people”, says Meyts. “Maybe there are no more than a few dozen around the world.”
In the magazine Nature Immunology the researchers presented their search strategy last week. They start from people who have been in contact with a covid patient for a long time without protection, without becoming ill themselves or testing positive. “We are especially looking for roommates of sick people, preferably even partners who have shared the bed with them.”
Genetic Blueprint
In these people it will be checked whether there is really no sign of infection in their blood. Then they must be able to prove that they have indeed been heavily exposed to the virus without protecting themselves. It must also be established that their partner or housemate was indeed infected with sars-CoV-2 and not with another respiratory virus.
Once the researchers have enough people who meet these conditions, they want to compare their genetic blueprint with that of a group of people who did get covid after having had unprotected long-term contact with a covid patient in their own home. The key question: are there differences between the genes of the people from the two groups that can explain why some are protected against Covid and the others are not?
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It wouldn’t be the first time that protective genes against an infectious disease have been found. For example, there are people who are naturally resistant to infection with the AIDS virus, HIV, because their white blood cells lack the ‘receptor’ on which this virus attaches. There are also people who are resistant to a malaria infection because they carry a rare ‘defect’ in their genes that prevents the malaria parasite from anchoring itself to the red blood cells.
Under normal circumstances, such defects do not offer these people an advantage, rather a disadvantage. For example, people with the gene defect that protects against malaria are more likely to suffer from sickle cell anemia, a painful blood disease. But when pathogens are around, the disadvantage turns into an advantage. “In the case of HIV, the discovery of such gene defects has even led to the development of a medicine,” says Meyts, who hopes that this will also be the case with Covid-19.
The researchers will not randomly search for gene defects, but will work in a targeted manner. For example, the ‘ACE receptors’, the projections on the cells of our nasal mucosa to which the coronavirus clamps, are a natural candidate. A defect in the genes that regulate the production of these receptors could explain why the coronavirus cannot enter people with this gene defect, no matter how often they are coughed.
“We also want to look at people who have an exceptionally strong immune defense,” says Meyts. “For example, people with a heavy overproduction of interferons (messenger substances that stimulate the immune system to action, ed.).That trait often leads to autoimmune diseases — conditions in which the immune system turns against the patient’s own tissues. But they may also stop the coronavirus.
Thousand candidates
The researchers hope to gather around a thousand candidates for their study. Anyone who thinks they meet the conditions for participation can apply, e-mailed the Dutchman András Spaan, who leads the project from Rockefeller University in New York. “There is no formal target group, but we mainly target adults. And the older, the more interesting.” After all, older people are particularly susceptible to Covid-19. If they manage to stay out of the grip of the virus, that is more meaningful than if a child manages to evade infection, the researchers suspect.
Meyts, who helps recruit candidates from Leuven, has already received ‘many hundreds’ of applications from all over the world in recent days. “From Brazil, Mexico, Russia, even two from Belgium.”
Meyts was already involved in a similar search for rare gene variants that influence susceptibility to Covid at the start of the Covid pandemic. “Then it was about mutations that make people more susceptible to Covid-19. So now we are looking for the opposite.”
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