Why do some people get SARS-CoV-2 infection, but others can fight it off? Why do some people develop serious COVID-19 disease after infection, while others only exhibit mild symptoms? A group of scientists from Regeneron has found some answers from the human genome.
In the largest trans-ancestry human exome sequencing study of COVID-19 to date, geneticists at the Regeneron Genetics Center have linked four gene locations and three specific genes to COVID-19 susceptibility and severity, according to findings presented at the American Society of Human Genetics virtual meeting.
Understanding the role of different genetic variations could help predict which people are more likely to be infected by the novel coronavirus and, perhaps more importantly, which COVID-19 patients require comprehensive care because they’re prone to severe outcomes.
The Regeneron team screened data from 868,021 individuals across six studies and four ancestries and studied their genetic differences in three categories: susceptibility to SARS-CoV-2 infection, requirement for hospitalization and severe outcomes such as death and ventilation.
Previous genomewide studies have identified two chromosome locations, or loci, that were implicated in different COVID-19 outcomes. In the current study, the researchers confirmed the role of the 3p21.31 locus, and the relationship was found to be stronger as disease severity increased.
However, the team failed to find a link with the other locus, called ABO, suggesting previous studies implicating it may have turned up false positives.
Beyond those two previously reported loci, the team also pinpointed three new loci and three genes associated with COVID-19. The GPS2, METTL7B and PLPPR3 genes were found to indicate whether a person was susceptible to SARS-CoV-2 infection. Among them, the GPS2 gene emerged in hospitalized cases. Three loci were correlated with disease severity: 22q21.1, 16q24.3 and 1p31.1, with the latter being mostly enriched in individuals of African ancestry, the Regeneron team showed.
In addition to the Regeneron study, scientists from the COVID-19 Host Genetics Initiative, a collaborative effort to study genetic data related to the disease, also fingered potential COVID-19-related genes.
After screening more than 14,000 positive cases, of which about 5,000 have been hospitalized, and over 1 million controls, a team at the Institute for Molecular Medicine in Finland identified a genetic variant on chromosome 3 that was strongly associated with disease severity but not susceptibility.
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. The genes are: CCR9, SLC6A20, CXCR6, LZTFL1, FYCO1 and IFNAR2.
The discovery of the association of the IFNAR2 gene on 22q21.1 corroborates that from the Regeneron group and other research teams that reported their findings on the journal preprint site medRxiv here and here.
Regeneron has been in the spotlight these days for its work on antibodies that hold potential as both treatments and preventive measures against COVID-19. Earlier this month, the company filed for an FDA emergency use authorization for an antibody cocktail, which was used as part of President Donald Trump’s treatment after he caught the virus.