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A new Cleveland Clinic study has identified genetic factors that may influence susceptibility to COVID-19. Published today in BMC Medicine, the study findings could guide personalized treatment for COVID-19.
While the majority of confirmed COVID-19 cases result in mild symptoms, the virus does pose a serious threat to certain individuals. Morbidity and mortality rates rise dramatically with age and co-existing health conditions, such as cancer and cardiovascular disease. However, even young and otherwise healthy individuals have unpredictably experienced severe illness and death. These clinical observations suggest that genetic factors may influence COVID-19 disease susceptibility, but these factors remain largely unknown.
In this new study, a team of researchers led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medicine Institute, investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms (variations in DNA sequences) in the ACE2 and TMPRSS2 genes. These genes produce enzymes (ACE2 and TMPRSS2, respectively) 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,” Cheng said. “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. They 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.
However, all investigations in this study were performed in general populations, not with COVID-19 patient genetic data. Therefore, Cheng calls for a human genome initiative to validate the team’s findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.
This study was supported by the National Heart, Lung, and Blood Institute and the National Institute of Aging (both part of the National Institutes of Health) as well as Cleveland Clinic’s VeloSano Pilot Program. Serpil Erzurum, M.D., chair of Cleveland Clinic’s Lerner Research Institute, and Charis Eng, M.D., Ph.D., chair of the Genomic Medicine Institute, are co-authors of the study.
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation, Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 83,000 employees worldwide are more than 6,600 salaried physicians and researchers, and 21,900 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,725-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, 300 outpatient facilities, including locations in northeast Ohio; Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2025, there were 15.9 million outpatient encounters, 343,000 hospital admissions and observations, and 336,000 surgeries and procedures throughout Cleveland Clinic’s health system. Visit us at clevelandclinic.org. Follow us at x.com/CleClinicNews. News and resources are available at newsroom.clevelandclinic.org.
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