Circulating angiotensin converting enzyme 2 and COVID-19

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.

Keywords: Circulating angiotensin converting enzyme 2, Coronavirus disease 2019, Disease severity, Clinical outcome, Severe acute respiratory syndrome coronavirus 2 infection

Core Tip: Recently, conflicting results on circulating ACE2 (cACE2) levels in coronavirus disease 2019 (COVID-19) patients vs healthy people with low cACE2 values were published. cACE2 levels and activity were shown to be increased in severe COVID-19 patients. However, others showed no change or decreased cACE2 in severe COVID-19 patients compared to pre-pandemic controls. Furthermore, it is unclear how SARS-CoV-2 infection and recovery impact the cACE2 level. cACE2 levels increased throughout the first 2 wk of the acute phase of COVID-19. cACE2 levels, on the other hand, were elevated for 1-3 mo after infection and decreased by 4 mo of the illness course. The purpose of this review is to look at the relationship between SARS-CoV-2 and cACE2. A variety of prospective therapeutic options for inhibiting SARS-CoV-2 infection is also explored.