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One of the lesser known aspects of Covid-19 refers to the course of the disease in infected people: some never develop any symptoms (asymptomatic), others develop very mild symptoms (pauci-symptomatic) while, among those who develop respiratory syndrome Some get away with a few days of fever, others need hospitalization and a minority even end up in intensive care. Why these huge differences between individuals if the virus is the same? Some answers may be in the genetics.
Male-female difference
The answer is probably in the genes: it is necessary to highlight the differences between women and men when one begins to enter into the mechanisms underlying the infection, differences that can be both hormonal and genetic. According to a document from the Istituto Superiore di Sanità, Sars-Cov-2 penetrates our cells by binding to a receptor called Ace2 to enter lung and heart cells, reducing its protective function from damage caused by infections, inflammation and stress. Estrogen increases the presence and activity of this receptor, while androgens play an opposite role. Ace2 may be more present in the lungs of women because it is encoded by overexpressed genes X chromosome.
The role of the X and Y chromosomes “The misunderstanding between the greater susceptibility of men compared to women, which is probably a misunderstanding, arises from the fact that the gene that codes for the main receptor of the Coronavirus is located on the X chromosome: women have two copies, the only man “, he explains exclusively for ilgiornale.it Prof. Fiorella Gurrieri, specialist in Medical Genetics at the Infectious Diseases Laboratory of the Policlino Gemelli and Senior Lecturer in Medical Genetics at the Bio-Medical Campus of the University of Rome. Here is the hypothesis by which we speak of greater protection of women and greater exposure of men. “It has been hypothesized that since women have two copies, they are more tolerant of functional defects in this receptor and are less susceptible to infection by Coronavirus. There is nothing scientific and nothing has been proven yet, but it is a “hypothesis based on this difference,” emphasizes the geneticist.
Because the woman is more protected. Gurrieri explains to us that, theoretically, it is the woman who should be more receptive (therefore more exposed) because, at a functional level, only one of the two X chromosomes works even in women and there would be no reason to think about a difference in function. between the two sexes. “The only hypothesis is that, given that the woman has two copies, if for some congenital reason one of the two works less or more, the woman is more protected because she also has another that is presumed to be functioning normally ”.
Here are the genetic variants. In recent weeks we have heard of variants of the virus (English, Italian, etc.), but those that in this case make the difference between one individual and another refer to genetics: large-scale genomic studies have found some ten genes that can modify the individual response to Covid. “In other words, there are variants potentially protective genetics and higher susceptibility genetic variants. This could explain why some people get more seriously ill than others who contract the infection but are not very symptomatic or not at all symptomatic and people who come into contact with the virus do not become infected ”, the researcher emphasizes.
What happens in families
Much effort will now be focused on groups of people who basically have half the genetic heritage in common: families, in each of which there is a variability of response to the virus. “We decided to study family groups of at least 4-5 people who have had the same exposure to the virus, as cohabitants, but with different or even no manifestations,” says Gurrieri-. We are analyzing the genetic variability between the different members of these. families focusing on the group of about forty genes known to be involved in the immune response. We have just started, before the next six months we will not have data. “The intrafamily study, for geneticists, is called” selection “because the members of a family already share 50% of their genetic material.
Genetics in world populations
“From the preliminary studies, it was seen that the gods cluster they are more likely to be infected than others: there is genetic influence but it has to be proven, they are more than the assumptions ”, Emanuele Montomoli, Professor of Public Health and president and founder of the Institute for Global Health at the University of Siena. The professor explained to us an Italian study carried out by the Ceinge-Advanced Biotechnology Institute, which operates in the field of molecular biology and advanced biotechnologies applied to human health. It is an excellence in Italy and abroad for Research and diagnosis of genetic diseases (hereditary and acquired).
“Sars-Cov-2 infection occurs due to a molecular mechanism in which the virus uses the Ace2 protein and the TMPRSS2 protein, which breaks the bond between Ace2 and Spike and allows the virus to enter the cell. Given Since these proteins are expressed by cells, I do not exclude that they can be expressed more or less significantly in cells of different populations“Montomoli told us.
Although there is no scientific evidence yet, the study by Campania researchers on genetic variants of 141,456 healthy subjects belonging to 17 different populations, including Africans, Europeans, Asians and Latinos, shows that the variant genetics of TMPRSS2 is more frequent in populations of Africa, Europe and Latin countries. “I hope that in the next period it will be proven with solid data but they are not crazy hypotheses, there is a scientific basis. There is also a Dutch study carried out in a claster of different populations with different genes that showed how different infections were and with different severity. There is something, it is not ruled out that something may also be linked to sex ”, concludes Montomoli.
The risks in man. One of the risk factors that would expose men more than women is linked to the presence of the protein TMPRSS2, present at high levels in tissues specific such as the prostate and testes: Epidemiological studies conducted in several countries, including China, Italy, and the United States, have shown that the incidence and severity of viral infections from Covid-19 and other viral infections, such as a simple flu , go hand in hand with the presence or massive absence of this protein, more present in males than females.
It’s the “fault” of the Neanderthals
It seems incredible, but what happens today in the Covid-genetics link has its origin beyond 60 thousand years ago, when Neanderthal man was still living: some of the genetic variants, in particular those present on the third chromosome, are also present in Neanderthals living in Croatia. This genetic package reached us Neanedrthals sapiens with whom we have mated several times in Eurasia once we left Africa. Consequently, this group of genetic variants of Neanderthal origin is particularly widespread in Asia (in 30% of the inhabitants), in Europe (in 8% of Europeans), but not in Africa and that, if confirmed, could also be part of the explanation of why in Africa, so far, the virus seems to have taken less root than in other countries.
If this group of genes protected Neanderthals from otherwise fatal bacterial or viral infections, those of us who inherit that haplotype (which is the combination of allelic variants along a chromosome or chromosome segment) are at risk if we get infected with Sars-CoV-2. , have an answer immune exaggerated that, not only does not protect you, but it exposes you to a more severe disease.
