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Source: COVID-19 Research  Jul 19, 2020  3 years ago
BREAKING! COVID-19 Research: Cleveland Clinic And Case Western Reserve Identify Genetic Factors That Influence COVID-19 Susceptibility
BREAKING! COVID-19 Research: Cleveland Clinic And Case Western Reserve Identify Genetic Factors That Influence COVID-19 Susceptibility
Source: COVID-19 Research  Jul 19, 2020  3 years ago
COVID-19 Research:  Researchers from Cleveland Clinic and Case Western Reserve University have identified genetic factors that may influence susceptibility to COVID-19.

These findings could pave the way for a personalized medicine approach for treating COVID-19 as it is emerging more day by day that COVID-19 is a highly complex disease with different pathogenesis paths in different individuals and there is not going to be a one treatment protocol that fits all as numerous factors are at play from genetics, underlying chronic medical conditions, previous viral or bacterial infections or exposure a patient had, the strain of the SARS-COV-2 coronavirus infecting the patient etc.
The research findings were published in the journal:  BMC Medicine. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01673-z
Although 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.
The team of researchers led by Dr Feixiong Cheng, Ph.D., Genomic Medicine Institute, investigated 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.
Studying in detail 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. 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.
The researchers found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. 
The fact that ACE2 is localized to Xp22.2 may help explain the observed male-associated risk. 
The researchers also noted that past studies have indicated specifically, several variants, including p.Met383Thr, p.Pro389His, and p.Asp427Tyr, have been reported to slightly inhibit the interaction between ACE2 and the spike protein of SARS-CoV-1 . https://www.embopress.org/doi/full/10.1038/sj.emboj.7600640
These research findings demonstrate a possible association between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, and indicate that a systematic investigation of the functional polymorphisms 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, Dr Cheng calls for a human genome initiative to validate his findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.
Dr Cheng told Thailand Medical News, "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. 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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