The Impact of Angiotensin-Converting Enzyme-2/Angiotensin 1-7 Axis in Establishing Severe COVID-19 Consequences

Abstract

The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.

Endotheliopathy in Acute COVID-19 and Long COVID

“…As mentioned above, this axis has a deleterious arm (ACE) and a protective arm (ACE2). Infection with SARS-CoV-2 mediates the downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2, by removing the protective arm, and, hence, increases angiotensin II [233]. Soluble (s)ACE2, the shed isoform of ACE2, preserves its catalytic activity; however, its role in viral entry remains as yet unclear.…”

Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial

“… 9 The angiotensin-converting enzyme 2 (ACE2) regulates RAS equilibrium by converting angiotensin-II (Ang-II), a ligand of the angiotensin receptor one (AT1R), into angiotensin-(1-7), a ligand of the Mas receptor (MasR). 9 , 10 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as the receptor to infect lung epithelial and endothelial cells. 11 , 12 , 13 Binding of SARS-CoV-2's spike protein to ACE2 may lead to a dysregulation of the RAS.…”

“… 14 , 18 , 19 , 20 , 21 We and others hypothesized that RAS modulation might thus limit the frequency of respiratory failure and mortality in hospitalized COVID-19 patients. 10 , 18 , 19 …”

Epicardial Adipose Tissue as a Prognostic Marker in COVID-19

“…Moreover, the direct cardiac injury of infected myocardial cells was mediated by the ACE2 receptors. This resulted in the release of immune-related factors, termed inflammatory storm, that could further lead to an imbalance of the oxygen supply (13). The association between EAT and the prognosis of COVID-19 might be caused by this cardiac involvement of the coronavirus.…”