key: cord-0812303-z6u7ewh9 authors: Imanpour, Hamed; Rezaee, Haleh; Nouri-Vaskeh, Masoud title: Angiotensin 1-7: A Novel Strategy in COVID-19 Treatment date: 2020-08-09 journal: Adv Pharm Bull DOI: 10.34172/apb.2020.068 sha: fe5bc6183071176c0e07a24bd3ee3f4a92d8c706 doc_id: 812303 cord_uid: z6u7ewh9 nan Coronavirus disease 2019 (COVID-19) is an emerging infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mortality rate of COVID-19 is high and there is no effective treatment for these patients to reduce the high hospitalization and mortality rates. The renin-angiotensin-aldosterone system plays a critical role in COVID-19 pathogenesis. 1 The sex difference in the mortality rate and complications of COVID-19, and also the more favorable prognosis of children leads to new hypotheses regarding the protective and harmful factors in the treatment of these patients. 2, 3 Angiotensin-converting enzyme (ACE) plays a role in innate and adaptive immune responses as well as converting angiotensin and affecting different physiological functions. 4 Understanding the expression of ACE on myeloid cells can be helpful in the treatment of infections. In comparison to adults, children have a higher level of ACE. 4 Although SARS-CoV-2 binds to ACE2 for entering the host cells, children are more immune against this virus; this is possibly due to a high level of ACE in children and its effects on immune responses. 4 Moreover, although children have a higher level of renin, angiotensin, and aldosterone compared with adults and also a higher amount of fluid in their bodies, they have lower blood pressures 5 ; one of the reasons behind this is the high level of angiotensin 1-7 that acts as a vasodilator and antiinflammatory agent against angiotensin 2. This is probably another reason for children's enhanced immunity against COVID-19. 6 Despite the low level of ACE2 in females in comparison to males, which protects the host against virus penetration, given the regulatory effect of estrogen on angiotensin type 2 receptor its effect on angiotensin 1-7 is more dominant. This is possibly the relative cause of women's increased immunity against COVID-19 infection. 7 Angiotensin receptor blockers (ARBs) are one of the main drugs that can provide high levels of ACE and angiotensin 1-7 at the same time. However, ARBs may also elevate the ACE2 level as the virus entry location, which should be considered in the prescription of ARBs. 8, 9 The administration of angiotensin 1-7 in adults may provide immunity against COVID-19 as in children. By injecting angiotensin 1-7, the renin-angiotensinaldosterone axis will become active to prevent a further drop in blood pressure, the ACE level will rise, and the ACE2 level will reduce owing to the accumulation of angiotensin 1-7. 8 This means that providing high levels of angiotensin 1-7 and ACE while reducing inflammatory bradykinin will be protective against ACE2, the entry site of the virus into the host cells. 8 Finally, the controlled injection of angiotensin 1-7 as a modulator of the reninangiotensin-aldosterone system and the compensation of a possible drop in blood pressure by infusion of intravenous fluids and alpha agonists may be able to reduce the severity of COVID-19 infection since the host is given an opportunity to induce specific immunity. Not applicable. COVID-19 and the raas-a potential role for angiotensin II? COVID-19: The gendered impacts of the outbreak Coronavirus disease (COVID-19) in children -what we know so far and what we do not? Angiotensin-converting enzyme in innate and adaptive immunity Renin and angiotensin levels in children Angiotensin-(1-7), and receptor MAS axis in the kidney Differences in angiotensin (1-7) between men and women Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients Interaction between raas inhibitors and ace2 in the context of covid-19 We declare no competing interests.