Team Uncovers Genetic Variants that Impact COVID-19 Susceptibility

Genetic variants may play a role in a person’s susceptibility to COVID-19, leading to a better understanding of which populations are most at risk of severe complications from the virus, according to a study published in BMC Medicine.

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Although the majority of COVID-19 cases result in mild symptoms, the virus does have a severe impact on certain patient populations. Morbidity and mortality rates rise significantly with age and co-existing health conditions, such as cancer and cardiovascular disease. However, even young and otherwise healthy people can experience severe illness and death.

There is some indication that genetic factors may impact COVID-19 susceptibility, but these factors remain largely unknown.

Researchers from Cleveland Clinic examined COVID-19 genetic susceptibility by analyzing DNA polymorphisms in the ACE2 and TMPRSS2 genes. These genes produce enzymes that enable the virus to enter and infect human cells.

“Because we currently have no approved drugs for COVID-19, repurposing already approved drugs could be an efficient and cost-effective approach to developing prevention and treatment strategies,” said Feixiong Cheng, PhD, of Cleveland Clinic’s Genomic Medicine Institute.

“The more we know about the genetic factors influencing COVID-19 susceptibility, the better we will be able to determine the clinical efficacy of potential treatments.”

Looking at 81,000 human genomes from three genomic databases, they found 437 genetic variants in the protein-coding regions of ACE2 and TMPRSS2. The group identified multiple polymorphisms in both genes that offer potential explanations for different genetic susceptibility to COVID-19 as well as for risk factors.

These findings demonstrate a possible association between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, indicating that identification of the functional polymorphisms of these variants among different populations could pave the way for precision medicine and personalized treatment strategies for COVID-19.

“A COVID-19 host genetics initiative is already underway to bring together the human genetics research community to generate, share, and analyze data in a search for the genetic determinants of COVID-19 susceptibility, severity, and outcomes,” the researchers stated.

However, all research in this study was performed in general populations, not with COVID-19 patient genetic data. Therefore, the group is calling for a human genome initiative to validate the team’s findings and identify new clinically actionable variants to accelerate precision medicine for COVID-19.

Teams across the healthcare continuum are conducting studies to determine the genetic impact of COVID-19. Researchers from the Nevada Genomics Center at the University of Nevada, Reno (UNR) are conducting genomic sequencing on samples from northern and southern Nevada that initially tested positive for COVID-19.

Researchers around the world are sharing genomes of the virus to establish its phylogenetic tree, which will help advance scientific understanding of COVID-19. Genomic analysis may also improve researchers’ understanding of factors related to severity of the disease.

“Probably the largest benefit will be to learn what strains of the virus are in northern and southern Nevada,” said Paul Hartley, PhD, director of the Nevada Genomics Center, one of several core laboratory facilities at the University. 

“The coronavirus genome can acquire mutations, and with the right amount of data, one can do epidemiological studies to understand how the virus may have spread.”