ACE2 and COVID-19: Genetic Insights into Viral Severity, Organ Complications, Infection Prevention, Therapeutic Strategies, and the Role of ACE2 as Biomarkers for Various Diseases

COVID-19 severity ranges from asymptomatic to moderate and severe cases that require intensive care. In addition to being the receptor of SARS-CoV-2, angiotensin-converting enzyme-2 (ACE2) has important functions in many organs. Here we reviewed one hundred eleven papers that dealt with ACE2 structure, genetic variations, expression patterns, association with organ complications, and the impact of these on COVID-19 and other diseases. A significant association was observed between COVID-19 mortality rates and coinfections with other viruses, which may occur due to alterations in ACE2 expression, a weakened immune response, or the onset of other severe conditions. Also, genetic variations and other factors have been proven to affect the stability of ACE2, alter its binding affinity with the virus spike protein, or increase/decrease ACE2 expression on the cell surface. All these can affect the entry of the SARS-CoV-2 virus into host cells. SARS-CoV-2 is involved in numerous organ complications, including the lung, cardiovascular system, central nervous system, gastrointestinal tract, reproductive system, kidney, liver, and eyes, both directly via virus invasion and indirectly via cytokine storms. ACE2 genome editing is considered a bright prevention technique for COVID-19. Blocking ACE2 has also been used as therapy to resist viral invasion. ACE2 is viewed as a potential biomarker for several diseases, including COVID-19, cardiovascular, inflammatory lung, Alzheimer, and cancer. Altogether, this allowed the conclusion that ACE2 represents an attractive enzyme to be further evaluated as a potential marker for the diagnosis of humans under high risk for both developing chronic diseases and acquiring SARS-CoV-2 infection. For a deeper understanding, we recommend a humanized animal knock-in study to validate the impact of common ACE2 alterations.