Angiotensin and COVID-19

Coronavirus disease 2019 (COVID-19) is a highly contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread rapidly worldwide since 2019, causing a high rate of deaths and disabilities. This virus exerts its pathogenicity through angiotensin-converting enzyme 2 (ACE2) receptor, expressed on a wide array of human cells. The infectious process starts with the engagement of ACE2 by protein S of the virus, which leads to the entry of viral genetic material within the host cell. COVID-19 induces imbalances of the renin–angiotensin system (RAS) manifesting with ACE upregulation and ACE2 downregulation. ACE converts angiotensin I into the peptide angiotensin (Ang) II, which binds to and activates Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors. The upregulation of the ACE/Ang II/AT1 signaling induces a series of deleterious effects in tissue and organs along with direct viral damage and proinflammatory cytokines. In general, Ang II mediates proliferation, inflammation, endothelial dysfunction, oxidative stress, and apoptosis. However, the negative effect of ACE signaling tends to be specific for all the organs (lungs, endothelium, kidneys, brain, and bowel) mainly affected by the virus. Given the key role of angiotensin in COVID-19, numerous experimental treatments have been tested to dampen the severe consequences of this unbalanced activation of RAS.