Why do some people with COVID-19 end up in the hospital with life-threatening infections while others develop only mild symptoms or none at all?
Well into the second year of the pandemic, doctors have identified a number of risk factors that make someone more likely to develop a severe case, including old age; diabetes; chronic kidney, liver, or lung disease; and being overweight or a smoker.
Now, an international study published in the journal Nature on Thursday concludes that genetic factors also increase the likelihood that someone will be infected with SARS-CoV-2 and develop a serious case. The study has more than 3,300 coauthors and was led partly by researchers from the Broad Institute of MIT and Harvard.
The genetic sleuths scoured data from 50,000 people who tested positive for the virus and provided DNA samples for 46 studies in 19 countries. Researchers pooled the data and compared it with that of 2 million other people who hadn’t been infected, in one of the largest so-called genome-wide association studies ever.
The authors found that 13 spots on the human genome are strongly associated with infection or severe illness. Genetic variations at some of those locations are also implicated in the development of lung cancer, pulmonary fibrosis, and certain autoimmune diseases.
Ben Neale, codirector of the Broad’s Program in Medical and Population Genetics and co-senior author of the study, said that although vaccines protect people from catching COVID-19, doctors still need better drugs to treat those who get infected. Identifying genetic markers associated with severe illness could help scientists develop those medicines.
“The better we get at treating COVID-19, the better equipped the medical community could be to manage the disease,” he said. “If we had a mechanism of treating infection and getting someone out of the hospital, that would radically alter our public health response.”
Genetic variations at two of the 13 locations pinpointed by the scientists occurred more frequently in patients of East Asian or South Asian ancestry than in those of European descent, underscoring the importance of collecting data from a diverse group of people.
The researchers involved in the 16-month-old effort, officially called the COVID-19 Host Genomics Initiative, plan to update their findings as they collect more data. They want to learn, among other things, whether genetic variations make someone more likely to become a COVID-19 “long-hauler,” with debilitating symptoms that linger for months.
Mark Daly, director of the Institute for Molecular Medicine Finland at the University of Helsinki and a member at the Broad Institute, helped start the international study. He and his colleagues, he said, hope “to get a good handful of very concrete therapeutic hypotheses in the next year.”
“Realistically, we will most likely be addressing COVID-19 as a serious health concern for a long time,” he said. “Any therapeutic that emerges this year, for example from repurposing an existing drug based on clear genetic insights, would have a great impact.”
Jonathan Saltzman can be reached at firstname.lastname@example.org.