They are the natural survivors of Covid-19. To the point that the Anglo-Saxons have found a new classification for them: the “Never Coviders”, namely people who have never contracted the Sars-CoV-2 virus after having been exposed to it many times. How many are there around the world? Mystery. For the simple and good reason that it seems more and more complicated to isolate them. Many of us can say that we have never tested positive or reported any symptoms. But no one can assure that he has never been (and will never be) ill. And things have become more complicated since the arrival, then the generalization of vaccination (54.6 million French people have received at least one dose) since we are now producing specific antibodies against Covid-19.
However, scientists remain convinced that some individuals do not become infected. In 2021, well after the start of the pandemic, an international consortium was created to target these people. “We first launched a vast study via an open questionnaire which elicited thousands of responses, explains Laurent Abel, who heads the international Human Genetics of Infectious Diseases laboratory at the Imagine Institute (Paris) and Rockefeller University ( New York). Today we have selected nearly 500 candidates, including around fifty in France, whom we follow regularly.”
Concretely, each volunteer must first show that they have been heavily exposed to the virus, for example in an intra-family setting: a couple whose spouse has had a heavy form while the other has not been infected; or health personnel largely in contact with patients throughout the pandemic. Then, of course, each volunteer must ensure that he has never been sick while not having experienced any positive test. Moreover, the entire cohort, as part of their follow-up, must regularly carry out serologies, in particular to check the levels of antibodies linked to vaccination and those linked to a natural infection. But most of the work is done from the selection of individuals who have received a saliva collection kit “so that we can explore their genome by sequencing it”, explains Laurent Abel. The researchers first compared the results between the “resistants” and the Covid patients. Then, they embarked on a vast hunt for variants and mutations.
This approach has already been successfully implemented in the past for other viruses for which natural resistance has been proven, such as norovirus. But the most well-known case remains HIV: “In the 1990s, we noticed that a handful of particularly exposed individuals were resistant to the infection, continues Laurent Abel. Work has shown that they were carriers a mutation in the gene that codes for a very specific receptor, called CCR5. Without it, we have seen that the virus cannot penetrate inside the body. And today, we know that 1% of Europeans lacking this small molecule are resistant to HIV.”
Could we find an equivalent for Sars-CoV-2 thanks to “Never Coviders”? The scientists were therefore interested in the different entry routes of the virus to infect cells. From 2020 they focused on the famous Spike protein and believed they detected that one of its receptors, called ACE2, could be a “gateway” to Covid, equivalent to the famous CCR5 for AIDS. “The ACE2 protein clearly plays a role in the physiology of Covid-19, but it is also involved in the regulation of a large number of cardiovascular, pulmonary and even renal functions, explains the researcher from the Imagine Institute. is probably not the only “gateway” so that we are interested in many other receivers.”
Foreign teams, notably American, have targeted another genetic system, HLA, certain variations of which have been associated with numerous diseases. From generation to generation, it evolves in response to pathogens. No doubt he plays a role in the production of antibodies, but he would not impose himself as a candidate who, at the origin, would block the virus. “With current technologies, we can genotype hundreds of thousands of variations and test them on the scale of the entire genome, explains Laurent Abel to show the extent of the task. We are therefore working on other very varied avenues.” In 2021, dozens of studies focused, for example, on people with blood group O, pointing to a lower risk of Sars-CoV-2 infections. “It plays in tiny proportions, underlines Laurent Abel. Our Grail would be to find variants which have more important effects to imagine therapeutic implications. But we are very far from it.” Fortunately, the “Never Coviders” genome is far from having revealed all its secrets.
