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One person can catch COVID-19 and scarcely notice any symptoms, while someone else can be held up in bed for days and another may require a lengthy stay in hospital. For over 4 million people, the disease has proved fatal.
Why the virus has this varied effect on different people has been one of the most burning questions of the pandemic. There are many well-established factors known to up the risk of falling severely sick with COVID-19 — from lifestyle and diet to age and sex — but a new study highlights how genetics may be an overlooked factor.
A large international study, published in the journal Nature, has discovered 13 loci (locations in the human genome) that appear to be linked to the susceptibility and severity of a COVID-19 infection.
The discoveries come from a network of researchers from the COVID-19 Host Genetics Initiative who analyzed the genetics of almost 50,000 patients with COVID-19 from 46 studies across 19 countries. This ongoing project, one of the largest genome-wide association studies of its kind, was launched in March 2020 and is just starting to produce the fruits of its labor. There’s still a lot more to discover about the “human genetic architecture of COVID-19,” but this research has already turned up some valuable insights.
Interestingly, two loci were more commonly found among patients of East Asian or South Asian ancestry than in those of European ancestry. Perhaps this insight might someday help to explain why certain ethnic groups have been hit harder by COVID-19 than others.
The study also found certain overlaps between variants that both increase the risk for severe COVID-19 and other diseases. For instance, DPP9, a gene also involved in lung cancer and pulmonary fibrosis, was associated with an increased risk of severe COVID-19. Notably, the same variant can increase the risk of a rare pulmonary disease characterized by scarring of the lung tissue. Similarly, TYK2, which is implicated in some autoimmune diseases, was also found to be linked to an increase in disease severity with COVID-19.
Another loci, ABO, dictates what blood type a person has and was found to be associated with a 9 to 12 percent increase in infection susceptibility. Perhaps this might have some relationship to the links between certain blood types and increased vulnerability to COVID-19.
"The human genome, and not only the viral genome, matters," Andrea Ganna, one of the lead authors of the study from the Institute for Molecular Medicine Finland at the University of Helsinki, said at a media conference. "Clearly, there is a role of genetics in COVID severity… it's one of the many risk factors."
There’s still a lot more to unearth from this research. Next on the agenda, the researchers hope to reveal why some people can become "long-haulers" who experience COVID-19 symptoms for months, while others appear to promptly recover. The team also hopes their work might point towards useful targets for repurposed drugs and pave the way for more therapeutics against COVID-19.
