It is a common fact that children are less susceptible to COVID-19 than adults, and they usually have milder forms often without symptoms, due to the age-related characteristics of their immune response and the features of the renin-angiotensin system (RAS). The recent studies have shown that the RAS elements are widely represented in the lungs, and they actively participate in the inflammation process in addition to their main vasoregulatory function. The cascade of RAS reactions is one of the key links in the pathogenesis of COVID-19, and it is analyzed from two positions: expression of ACE2 receptors and polymorphisms of certain genes of this system. The studies have demonstrated that the ACE2 transmembrane protein is both the “entry gate” for the virus, and it also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7) with vasodilating properties. A higher content of ACE2 in children as compared to that in adults maintains the RAS system balance and prevents the development of complications. It has been also found that certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) can cause the imbalance of RAS components, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift of the vasoconstrictor, proliferative and profibrotic mechanisms. The patients with certain genetic polymorphisms of NOS genes regulating vascular tone, cell growth and proliferation may have a genetic predisposition to the development of severe forms of COVID-19. © 2020 National Academy of Pediatric Science and Innovation. All rights reserved.