Identification of Genetic Factors Influencing COVID-19 Susceptibility Could Pave Way for Personalized Treatment

Researchers at the Cleveland Clinic (Cleveland, OH, USA) have identified genetic factors that may influence susceptibility to COVID-19, which could guide personalized treatment.

Clinical observations of confirmed COVID-19 cases suggest that genetic factors may influence COVID-19 disease susceptibility, but these factors remain largely unknown. The team of researchers conducted to study to investigate genetic susceptibility to COVID-19 by examining DNA polymorphisms (variations in DNA sequences) in the ACE2 and TMPRSS2 genes. ACE2 and TMPRSS2 produce enzymes (ACE2 and TMPRSS2, respectively) that enable the virus to enter and infect human cells.

Looking at ~81,000 human genomes from three genomic databases, they found 437 non-synonymous single-nucleotide variants in the protein-coding regions of ACE2 and TMPRSS2. They identified multiple potentially deleterious polymorphisms in both genes (63 in ACE2; 68 in TMPRSS2) that offer potential explanations for different genetic susceptibility to COVID-19 as well as for risk factors. Several ACE2 variants were found to be associated with cardiovascular and pulmonary conditions by potentially altering the angiotensinogen-ACE2 interaction. In addition, germline deleterious variants in the coding region of TMPRSS2, a key gene in prostate cancer, were found to occur in different cancer types, suggesting that oncogenic roles of TMPRSS2 may be linked to poor outcomes with COVID-19.

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

“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 Dr. Feixiong Cheng, PhD, Genomic Medicine Institute, who led the team of researchers for the study. “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.”

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