Elite controllers manage to get rid of Covid-19 – 07/19/2023 – Science

Some people’s bodies are capable of defeating Sars-CoV-2, the virus that causes Covid-19, without showing any symptoms of the disease, and the explanation may lie in their DNA, shows a new study. In these individuals, the variant of a gene linked to the body’s defense system allows the viral invader to be recognized and fought with exemplary efficiency.

The data are in an article that has just been published in the scientific journal Nature. The work’s first author is the Brazilian Danillo Augusto, a professor at the University of North Carolina at Charlotte (USA) and also at the Graduate Program in Genetics at UFPR (Federal University of Paraná).

“Right at the beginning of the pandemic, attention was drawn to the fact that many people did not develop symptoms of Covid-19, and we imagined that there could be some protective genetic factor. [por trás disso]”, explained Augusto to the Sheet. “However, as people without symptoms typically do not seek medical attention, we knew it would be very difficult to collect samples from them.”

To get around this difficulty, he and his colleagues took advantage of an existing database, the US national registry of voluntary bone marrow donors. The advantage is that the directory already included information about the volunteers’ DNA, since this influences the compatibility of donations.

“We sent thousands of emails inviting these people to download a cell phone application. Every day, they reported whether they had had any symptoms and also shared the results of virus detection tests”, says the researcher.

Among the donor registry data was information about a group of genes collectively referred to by the acronym HLA (for “human leukocyte antigens”, in English). These genes contain the recipe for the production of molecules whose function could be compared to that of an organism’s self-defense course.

When, for example, a virus invades a new victim, the HLA molecules present viral particles to the so-called T cells of the body’s defense system. This triggers a multi-pronged counterattack, which, with any luck, can lead to the attacker’s defeat.

Previous analyzes already indicated that variation in HLA genes could be relevant to the course of infection by the Covid-19 virus. The team then cross-referenced the genetic data of the people who responded to their contacts – around 1,500 donors – with their reports on the diagnosis of the disease. It was then that it became clear that an allele (genetic variant) designated by the acronym HLA-B*15:01, present in more or less 10% of people of European origin in the sample, was associated with asymptomatic infections.

To be exact, those who carried the allele were nearly three times more likely to have no symptoms of the disease. In the case of individuals who carried two copies of the allele –one inherited from the father and the other from the mother–, the effect seems to be even clearer: these people were eight times more likely to have no symptoms.

If the work had been restricted to this type of analysis, the data could be nothing more than a statistical association, which does not necessarily show that the presence of the DNA variant is the cause of the infection without symptoms of Covid-19. Therefore, the team integrated by the Brazilian conducted a series of other tests. Among them, the most important was the analysis of human cell cultures obtained long before the pandemic, that is, without any chance of previous contact with Sars-CoV-2.

“We observed that the cells of individuals who have this DNA variant had immunological memory against a particle of the Covid-19 virus, even without having had contact with the virus”, explains Augusto. “So they had a very quick and effective immune response, eliminating the virus before it caused symptoms.”

It turns out that this memory of the defense system was activated because of the similarity between certain molecules of Sars-CoV-2 and those of other coronaviruses that have been circulating for much longer in the human population, causing a good part of what we call common colds. These molecules are classified as evolutionarily “conserved”, that is, they are common to a wide range of different coronaviruses that evolved from the same common ancestor.

Better understanding the interaction between the variant and the conserved portions of the coronavirus genome may inspire, in the future, more effective vaccines against all symptoms of Covid-19, although the current ones are already very useful against severe symptoms and risk of death. The team also intends to verify whether the protection mechanism is present in populations of non-European origin.