From the earliest days of the pandemic, it has been clear that underlying biological factors have played a part in determining why some people with coronavirus are asymptomatic while others develop life-threatening illness. Combing through the genome, a group of Regeneron scientists have tied COVID-19 severity and susceptibility to certain genes associated with the immune system’s response. In particular, Regeneron geneticists identified four gene areas (loci) and three particular genes that may affect vulnerability.
This was no simple task. So far, the Regeneron team's data represents the most comprehensive survey of genetic variation associated with COVID-19. The Regeneron workforce screened data from 868,021 individuals, spanning six studies and four ancestries. The scientists studied genetic differences in three categories: susceptibility to SARS-CoV-2 infection, requirement for hospitalization, and severe outcomes such as death and ventilation.
On the basis of these results, the team confirmed a previously identified gene area (the 3p21.31 locus) associated with COVID-19, grimly noting that the relationship was found to be even stronger as disease severity increased. The group failed to replicate an association between COVID-19 and the ABO locus, suggesting that the previous finding may have been a false positive.
Beyond previously reported associations, the team pinpointed three new gene areas (22q21.1, 16q24.3, and 1p31.1) which correlated with disease severity, the latter having been determined to be mostly enriched in individuals of African ancestry. On top of that, three new particular genes (GPS2, METTL7B, and PLPPR3) were also found to indicate whether a person was susceptible to SARS-CoV-2 infection, the Regeneron team showed.
In addition to the Regeneron study, scientists from the COVID-19 Host Genetics Initiative, an international effort to study genetic data related to the disease, also disclosed potential COVID-19-related genes. Likewise, in another COVID-19 related study, a partnership among scientists from Yale University, Vanderbilt University Medical Center, Scripps Research, and others named six genes in two chromosomic regions as related to COVID-19 outcomes in hospitalized patients. Combined, these studies point to exciting areas for future research.
As COVID-19 continues to affect populations globally, it seems that there's no better place to look for answers than our own genetic blueprint. Studying genetic variations can reveal information about biological pathways involved in disease susceptibility or resistance, thus opening the way to testing drugs that target those pathways. More discoveries from the genetics community may also help identify individuals at unusually high risk for infection or complications, allowing us to adopt more proactive strategies in the future.
