Angiotensin-Converting-Enzyme 2 and Renin-Angiotensin System Inhibitors in COVID-19: An Update

Abstract

Ever since its outbreak, Corona Virus Disease 2019(COVID-19) caused by SARS-CoV-2 has affected more than 26 million individuals in more than 200 countries. Although the mortality rate of COVID-19 is low, but several clinical studies showed, patients with diabetes mellitus (DM) or other major complication at high risk of COVID-19 and reported more severe disease and increased fatality. The angiotensin-converting-enzyme 2 (ACE2), a component of renin-angiotensin-system (RAS); acts on ACE/Ang-II/AT1recptor axis, and regulates pathological processes like hypertension, cardiac dysfunction, Acute Respiratory Distress Syndrome (ARDS) etc. The progression of T2DM and hypertension show decreased expression and activity of ACE2. There are several treatment strategies for controlling diabetes, hypertension, etc; like ACE2 gene therapies, endogenous ACE2 activators, human recombinant ACE2 (hrACE2), Angiotensin-II receptor blockers (ARBs) and ACE inhibitors (ACEi) medications. ACE2, the receptors for SARS-CoV2, facilitates virus entry inside host cell. Clinicians are using two classes of medications for the treatment of COVID-19; one targets the SARS-CoV-2-ACE2 interaction, while other targets human immune system. The aim of this review is to discuss the role of ACE2 in diabetes and in COVID-19 and to provide an analysis of data proposing harm and benefit of RAS inhibitor treatment in COVID-19 infection as well as showing no association whatsoever. This review also highlights some candidate vaccines which are undergoing clinical trials.

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy

“…ACEI and ARB are widely administered to patients with heart failure, which reduces heart stress and leads to increased ACE-2 expression and activity. However, increased ACE-2 levels may also make cells more susceptible to SARS-CoV-2 infection [210]. Thus, establishing a therapeutic time window for ACE-2 targeting in COVID-19 patients with cardiovascular diseases (CVDs) is a significant challenge.…”

“…Several potential therapeutic strategies targeting ACE-2 have already been proposed to combat COVID-19. However, because of the critical metabolic and hemodynamic roles of ACE-2, including the regulation of glucose homeostasis [212] and the cleavage of angiotensin I and angiotensin II [210], these approaches may lead to severe clinical problems [213]. Therefore, transmembrane protease serine 2 (TMPRSS2), another main co-factor needed by the SARS-CoV-2 to enter human cells, might be an alternative target for COVID-19 [214].…”

Oxidative Stress and Inflammation in SARS-CoV-2- and Chlamydia pneumoniae-Associated Cardiovascular Diseases

“…The SARS-CoV-2 infection of a broad range of different tissues in the host is explained by the expression of high levels of Angiotensin-converting enzyme (ACE)-2 receptors on the cell surface [22]. In this regard, ACE2 has recently acquired importance in the pathogenesis of SARS-CoV-2 infection for its role as a functional point of entry for the virus by binding to its surface S protein [22] as well as for its important regulatory role in the renin-angiotensin-aldosterone system (RAAS) [23].…”

“…The SARS-CoV-2 infection of a broad range of different tissues in the host is explained by the expression of high levels of Angiotensin-converting enzyme (ACE)-2 receptors on the cell surface [22]. In this regard, ACE2 has recently acquired importance in the pathogenesis of SARS-CoV-2 infection for its role as a functional point of entry for the virus by binding to its surface S protein [22] as well as for its important regulatory role in the renin-angiotensin-aldosterone system (RAAS) [23]. ACE2 is also expressed in the heart and the vascular endothelium, and SARS-CoV-2 has been shown to bind with high affinity to these receptors [22,23], invading and replicating within myocardial and endothelial cells as well as pericytes [24,25], leading to tissue damage.…”

The Crosstalk between SARS-CoV-2 Infection and the RAA System in Essential Hypertension—Analyses Using Systems Approach

“…On the other hand, there are significant studies that have strengthened professional society guidelines for not discontinuing ACEIs/ARBs treatment in COVID-19 patients when clinically indicated [ 47 ]. Thus, the treatment with ACEI and ARB drugs does not need to be altered for COVID-19 patients [ 48 , 49 ].…”