Single-cell RNA sequencing was used to analyze the SARS-CoV-2 responses of 22 blood cell types. These data were then combined with serological and genetic information collected from the same individuals, making it possible to assess the degree of disparity between populations in terms of their immune responses to SARS-CoV-2, and to identify contributing factors.

Scientists have identified around 900 genes that respond differently to SARS-CoV-2 between populations. Using statistical genetic analyses, they show that these disparities are mainly due to variation in blood cellular composition: the proportion of each cell type differs from one population to another. We know that blood cell composition can be influenced by environmental factors such as exposure to cytomegalovirus (a human infection of the herpes family, which is usually harmless) and cytomegalovirus prevalence varies widely among populations: Central Africans present 99% seropositivity, in contrast to only 50% in East Asians and 32% in Europeans. The team found that an individual's environment, specifically latent cytomegalovirus infection, will thus influence the immune cell response to SARS-CoV-2.

Furthermore, the scientists have identified around 1,200 human genes whose expression in response to SARS-CoV-2 is under the control of human genetic factors and the frequency of the alleles that regulate these genes can vary between the populations studied. Using population genetics approaches, they have identified recurrent selection events targeting genes involved in anti-viral functions.

By comparing the 1,200 genes identified with the Neanderthal genome, scientists have discovered dozens of genes that both alter antiviral mechanisms and result from ancient introgression between Neanderthals and modern humans (Homo sapiens). "Previous studies have shown the link between some of the genes identified in our study and the severity of COVID-19. Our comprehensive population-based study highlights the direct impact of genetic variants governing immune responses to SARS-CoV-2 on the severity of COVID-19. It also establishes links between past evolutionary events, such as natural selection or Neanderthal admixture, and current population disparities in immune responses and disease risk," explains Lluis Quintana-Murci, Head of the Human Evolutionary Genetics Unit at the Institut Pasteur, Professor at the Collège de France and co-last author of the study.

"By identifying the precise cellular and molecular pathways of the genetic variants associated with COVID-19 severity, this study paves the way for precision medicine strategies that could either identify high-risk individuals or facilitate the development of new treatments," adds Darragh Duffy, Head of the Institut Pasteur's Translational Immunology Unit.

Source: https://www.news-medical.net/news/20230824/Genetics-and-environment-influence-immune-responses-to-SARS-CoV-2.aspx