COVID-19 and ACE2 Receptor in Different Tissues: From Pathophysiologic Function To Therapeutic Responses

SARS-CoV-2, the virus responsible for COVID-19, is characterized by its high transmission rate, leading to a global pandemic. Millions of people have lost their lives due to the infection caused by this virus. The ability of the virus to spread rapidly and infect large numbers of people has highlighted the need to understand its mechanisms of infection. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for SARS-CoV-2 cell entry. SARS-CoV-2 exhibits a high affinity to this receptor and shows high infectivity, leading to an explosive increase in patients infected with COVID-19. ACE2 is the carboxypeptidase homolog of ACE, which produces angiotensin II, the main active peptide of the renin-angiotensin system. From a pathophysiological perspective, this system regulates vital processes across different organs. Additionally, ACE2 enzyme activity could play a protective role against acute respiratory distress syndrome (ARDS) caused by viral pneumonia. Upon infection, SARS-CoV-2 downregulates the expression of ACE2, which is possibly related to the pathogenesis of ARDS. Since this receptor is present in various other tissues such as the heart, kidney, gastrointestinal tract, reproductive system, and sensory organs, it may contribute to pathological symptoms in these organs. Thus, ACE2 is not only a receptor for SARS-CoV-2 but may also play a crucial role in various aspects of the pathogenesis of COVID-19 and potential post-COVID-19 syndromes. Administering ACE2 could competitively bind to SARS-CoV, thereby reducing viral spike protein from attaching to transmembrane ACE2 and consequently reducing viral cell entry into cells and COVID-19 symptoms. In this review, we first examine the role of ACE2 in the pathophysiology of SARS-CoV-2 across different tissues and propose treatment strategies for COVID-19 that involve ACE2.