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A prior infection by another virus, the cytomegalovirus, but also the genetic diversity of human populations play a role in the variable immune reactions to Covid-19, according to a study published this Wednesday in the journal Nature.
French scientists (Institut Pasteur, CNRS, Collège de France), supported by international researchers, have studied the variations in immune responses to SARS-CoV-2 depending on the origins. They exposed immune blood cells obtained from 222 healthy donors from Central Africa, Western Europe and East Asia to the virus.
A cytomegalovirus infection could worsen the severity of Covid
Using single-cell RNA sequencing, they analyzed the SARS-CoV-2 responses of 22 blood cell types and combined these results with serological and genetic information about the same individuals.
Scientists have thus identified around 900 genes with different behavior depending on the population. Variations mainly due, according to them, to the cellular composition of the blood. However, among the factors influencing these cellular differences is exposure to cytomegalovirus (infection, generally harmless, of the herpes family). 99% of the population of Central Africa is seropositive for cytomegalovirus, compared to 50% of that of East Asia and 32% of Europeans.
A latent cytomegalovirus infection could thus increase the risk of Covid severity. Genetic singularity also plays a role: it controls the expression of around 1,200 genes in the face of Covid, according to the study.
So, “Natural selection has influenced current immune responses to SARS-CoV-2, particularly in people of East Asian descent, where coronaviruses engendered strong selection pressures around 25,000 years ago”according to Maxime Rotival (Pastor), co-lead author with Lluis Quintana-Murci.
A link with our Neanderthal ancestors
The study also establishes a link between a part of prehistoric heritage and immune disparities. Between 1.5 and 2% of the genes of Europeans and Asians are derived from Neanderthals. By comparing some of their results and the genome from Neanderthals, the scientists discovered dozens of genes that affect antiviral mechanisms and result from ancient crosses between Neanderthals and Homo sapiens.
“Previous studies have shown the link between some of the genes identified in our study and the severity of COVID-19. This inclusive and diverse study thus highlights the direct impact of genetic variants influencing immune responses to SARS-CoV-2 on the severity of COVID-19 disease. It also draws connections between past evolutionary events, such as natural selection or Neanderthal interbreeding, and current demographic disparities in immune responses and disease risk.”explains Lluis Quintana-Murci, head of the Human Evolutionary Genetics Unit at the Institut Pasteur and professor at the Collège de France, co-lead author of the study.
This work is indeed a new illustration of the contributions of genetics to understanding the pandemic. Still in mid-July, a study in Nature showed that people with a certain genetic variant are twice as likely not to get sick when they contract Covid-19.
Paleogenetics also confirms its interest. In 2020, two years before his Nobel in medicine, the Swede Svante Pääbo had highlighted, with other researchers, the presence of a particular portion of DNA, inherited from Neanderthal man, in the most ill patients. severe Covid. This portion of DNA is more common in populations from South Asia.