Why do some people infected with SARS-CoV-2 have either no or negligible symptoms, while others sicken and die?

Scientists who’ve pinpointed several genetic markers associated with severe COVID-19 say their findings could provide answers to that important question — and targets for future treatments.

The investigators spotted 13 locations in human DNA that are strongly associated with SARS-CoV-2 infection or severe COVID-19.

The international team of researchers also identified non-genetic risk factors, such as smoking and obesity.

The results are from one of the largest genome-wide association studies ever conducted. It included nearly 50,000 COVID-19 patients and a control group of 2 million uninfected people.

Locations associated with severe COVID-19 include: the FOXP4 gene, which is linked to lung cancer; the DPP9 gene, associated with lung cancer and pulmonary fibrosis; and the TYK2 gene, which is connected with some autoimmune diseases.

Inhibiting such genes could be potential treatments for preventing severe COVID-19, according to the authors of the study published online July 8 in the journal Nature.

The research is from the COVID-19 Host Genomics Initiative, which currently includes more than 3,300 authors and 61 studies from 25 countries.

While vaccines protect against infection, treatment for COVID-19 could be significantly improved and that can be guided by genetic analysis, said study co-senior author Ben Neale. He is co-director of the Program in Medical and Population Genetics at the Broad Institute of MIT and Harvard, in Cambridge, Mass.

Improved treatments could help shift the COVID-19 pandemic to a disease that is more localized and present at consistent, but low, levels — much like the flu, according to Neale.

“The better we get at treating COVID-19, the better equipped the medical community could be to manage the disease,” Neale said in an institute news release. “If we had a mechanism of treating infection and getting someone out of the hospital, that would radically alter our public health response.”

The researchers will continue to study more data to try to determine what differentiates so-called “long haulers” — patients whose COVID-19 symptoms persist for months — from others, and to identify additional loci associated with infection and severe disease.

Mark Daly is COVID-19 Host Genomics Initiative co-founder, director of the Institute for Molecular Medicine Finland, University of Helsinki, and a member at the Broad Institute. Daly said, “We’d like to aim 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. Any therapeutic that emerges this year, for example from repurposing an existing drug based on clear genetic insights, would have a great impact.”

More information

The U.S. Centers for Disease Control and Prevention has more on COVID-19.

SOURCE: Broad Institute of MIT and Harvard, news release, July 8, 2021

Source: HealthDay