Researchers Suggest Genetics Might Be Behind Patient Response to COVID-19

Genetics

COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, affects different people differently. As has been broadly noted, about 85% of cases are mild, while others can become fatally ill. Although the fatality rate is highest in the elderly and immunocompromised, it also can kill the relatively young and healthy, which is a somewhat unexpected aspect of the disease.

As the pandemic progresses, researchers are attacking the virus from every angle, and also learning more and more about how and why the virus affects who it does.

“We see huge differences in clinical outcomes and across countries,” said geneticist Andrea Ganna of the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM).

For example, studies have found that risk factors include diabetes, hypertension, cardiovascular disease and lung disease. A study out of the University of Copenhagen, in Denmark, found that “diabetes was a comorbidity in 22% of 32 non-survivors in a study of 52 intensive care patients. In another study of 173 patients with severe disease, 16.2% had diabetes, and in further study of 140 hospitalized patients, 12% had diabetes.”

Diabetes was also a comorbidity in the previous SARS and MERS coronavirus infections, as well as in the severe influenza A H1N1 pandemic in 2009. The study indicated that hypertension was a comorbidity in COVID-19 in about 20% of cases, 16% of cardiovascular disease, and 6% for lung disease.

Diabetic patients, the study notes, “are at increased risk of infections including influenza and for related complications such as secondary bacterial pneumonia. Diabetes patients have impaired immune-response to infection both in relation to cytokine profile and to changes in immune-responses including T-cell and macrophage activation.” Many diabetics are obese, and obesity is also a risk factor for severe COVID-19.

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Ganna is involved in a project that is similar to several ongoing around the world—collecting DNA from COVID-19 patients from a variety of patients around the world and comparing the DNA, trying to identify the genetic factors involved.

So far, there are a few suspects. One is the gene that codes for the angiotensin-converting enzyme 2 (ACE2), a cell surface protein that the coronavirus uses to enter cells in the lungs. It’s possible that variations in the ACE2 gene that change the receptor make it easier—or more difficult—for the coronavirus to enter the cells in the airways, said Philip Murphy of the National Institute of Allergy and Infectious Diseases.

Ganna’s project is affiliated with the Broad Institute. With FIMM director Mark Daly, they created a website, the COVID-19 Host Genetics Initiative, whose goal is to “bring together the human genetics community to generate, share and analyze data to learn the genetic determinants of COVID-19 susceptibility, severity and outcomes.”

The hope is that the results will provide insights on who is at unusually high or low risk, and to give clues to possible drugs that can be repurposed to prevent or treat the disease. A number of the world’s biggest biobanks are planning to participate, including the UK Biobank, deCODE Genetics and FinnGen.

Jean-Laurent Casanova at Rockefeller University specializes in identifying rare genes that make healthy children susceptible to specific serious illnesses. Casanova is working with a network of pediatricians globally to find young people who developed COVID-19 bad enough to need intensive care. COVID-19 has been notable for its relative lack of cases in children.

“We study exclusively patients who were previously healthy,” Casanova said, who are under 50, because their serious COVID-19 cases are more likely to have a genetic basis.

Researchers are also interested in variations in the human leukocyte antigen genes. These genes affect how the immune system responds to viruses and bacteria. For example, a research group claimed that people with type O blood may be protected from the virus.

“We’re trying to figure out if those findings are robust,” said Stanford University geneticist Manuel Rivas, who is participating in Ganna’s project.

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