Two Genetic Regions Linked with Severe COVID-19


It’s not yet clear why some people infected with SARS-CoV-2, the virus that causes COVID-19, get really sick, while others have only mild symptoms. There’s some evidence that chronic health conditions—such as hypertension and diabetes can play a role, and scientists know that people’s genes can influence how their bodies react to other viruses. In a preprint posted to medRxiv on June 2, researchers describe a genome-wide association study (GWAS) of samples from 1,610 hospitalized patients with COVID-19 and 2,205 healthy controls. The authors identified variants in two regions—the locus that encodes blood type and a multi-gene cluster on chromosome 3—that were linked to respiratory failure during SARS-CoV-2 infection.

“We know that people vary in their susceptibility to infectious diseases, and variation in the human genome plays a . . . role in that susceptibility,” Charlotte Houldcroft, who studies interactions between viruses and hosts at the University of Cambridge and was not involved in the work, writes in an email to The Scientist. “A genome-wide association study is a very good way to look at lots of variants across the human genome all at once, without a preconceived idea about which genes might be involved.”

Finding anything meaningful in a GWAS depends upon having enough genomes to analyze. In a pandemic, that’s especially tricky. According to Andre Franke, a geneticist at Christian-Albrechts-University of Kiel in Germany, it was the connections that his colleague Tom Hemming Karlsen, a physician-scientist at the University of Oslo in Norway, has to clinicians and researchers in COVID-19 hot spots in Spain and Italy that made the study possible.

See “DNA Could Hold Clues to Varying Severity of COVID-19”

The research team collected, genotyped, and analyzed samples from 775 patients and 950 controls from Spain and 835 patients and 1,255 controls from Italy. The patients were all hospitalized and were either in need of mechanical ventilation or on supplemental oxygen, both of which the researchers categorized as respiratory failure. They pulled out two genomic regions in which certain variants showed up more in patients hospitalized for COVID-19 than in unhospitalized people from the same geographic region.

Ideally, a GWAS analysis would analyze the genomes of people with COVID-19 and compare those who didn’t get very sick to those who experienced severe symptoms, instead of using population-based controls whose exposure to the virus is unknown, says Priya Duggal, a genetic epidemiologist at the Johns Hopkins Bloomberg School of Public Health who did not participate in the study. Nevertheless, “it’s really incredible to see how much work was done in such a short period of time. In about two months, these investigators moved from cases being identified in the hospitals to being genotyped to the identification of two putative regions.”

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