Different populations respond to COVID in different ways, and not for the reason you might think
One of the enduring mysteries of the COVID pandemic is why the SARS-CoV-2 virus affects some people differently than others: one person may get “long COVID” while another person may not have any symptoms. In this paper from Nature, an international team of researchers discovered that the effects of COVID don’t just vary between individuals — they also differ between populations.
In this study, researchers collected certain types of white blood cells from people of Central African and West European descent who had never been infected with SARS-CoV-2. The researchers then exposed some of these white blood cells to the virus in a laboratory. They found that different sets of genes were activated or inhibited in cells that were infected with the virus as compared to cells that weren’t. Interestingly, they also found that gene expression in infected white blood cells from African donors differed from gene expression in infected white blood cells from European donors.
Why did the virus affect cells from African and European donors in disparate ways? It’s not for the reason you might expect. While the authors of the study did find some genetic differences that influenced how cells from each population responded to the SARS-CoV-2, they believe that the most important factor is not genetic but environmental: infection by a different virus.
Cytomegalovirus is a very common virus in the herpes family: it’s basically a less famous sister of herpes I and II. Although it can cause problems for the fetus during pregnancy, most people infected with cytomegalovirus experience mild illness or no symptoms. You are probably infected with cytomegalovirus: at least half of the people in the United States have been infected by age 40, and infection rates tend to be higher in developing nations. In this study, 99% of the African donors were infected with cytomegalovirus as compared to 31% of the European donors.
Why would infection with cytomegalovirus affect the way a person responds to SARS-CoV-2? People who are infected with cytomegalovirus tend to express different proportions of the various types of white blood cell than people who are not infected. Each type of white blood cell responds to viral infection using a distinctive sets of genes. People infected with cytomegalovirus had a greater proportion of natural killer cells and T cells than non-infected people. Both of these cell types recognize and kill infected cells. To string it all together: African donors were more likely to be infected with cytomegalovirus, which caused them to have higher proportions of certain types of white blood cells, which caused them to respond to infection with a second virus — SARS-CoV-2 — in a different way.
Why do we care? Understanding how a person responds to infection by SARS-CoV-2 (and why) can help determine the way that patients are treated and inform the development of new therapies. For example, future research may determine that COVID patients with cytomegalovirus respond best to a different set of treatments than COVID patients without cytomegalovirus.
A semi-political side note: Unfortunately, all of the data in this study was collected from male subjects. Including only male subjects is a common practice in scientific studies. It is possible — perhaps even likely — that data collected from female and intersex individuals would follow the same trends as were seen in this study. However, it is also possible that they would not. Equitable medical treatment requires equitable research practices. We need to stop just studying men.
