SARS-CoV-2: ACE inhibitors, disastrous or desirable?

Abstract

<jats:p>Background: The world has a current total of 6,663,304 confirmed cases of COVID-19 with a death count of 392,802 deaths according to the WHO (6 June 2020). Various risk factors for the acquisition and subsequent development of deadly complications due to the virus have been established. One such risk factor is the presence of cardiovascular disease, particularly hypertension as a comorbidity. It must be noted that JNC 8 advise the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers as first line drugs for the management of hypertension. ARDS is caused by the activation of angiotensin I, angiotensin II and AT1 receptor pathway, however stimulation of Mas receptor, MRGPR receptors, AT2 receptor and the ACE-2-angiotensin (1-7), pathways is found to be defensive. Mas receptor exerts an inhibitory effect on inflammation and cellular growth and vascular mechanisms. This research aims to examine the relationship between ACE inhibitors and the risk of COVID-19 infections with the goal of determining whether this relationship is spurious in association or whether it is causative in nature? More specifically, in this research article we will determine whether the SARS-CoV-2 virus has an affinity for ACE 2 receptors in humans. Furthermore, it will be determined whether ACE inhibitors would inhibit or facilitate an imminent COVID-19 infection in individuals as well as to determine whether patients currently using ACE inhibitors should continue or discontinue the drug therapy in order to minimize their susceptibility to acquiring COVID-19, and whether patients should start ACE inhibitor therapy if required during this pandemic.&#x0D; Conclusion: It is evident that ACE 2 receptors are the portal of entry for SARS-CoV-2. It is recommended that the use of RAAS inhibitors, viz ACE inhibitors and angiotensin receptor blockers is not stopped or decreased despite the ongoing pandemic as the results thereof may lead to the worsening of the patient’s comorbidity and may hasten death.</jats:p>

New challenges to renin-angiotensin-system in COVID-19 pandemic

“…There was no evidence for any increased or reduced risk of COVID-19 patients in intensive care unit (ICU) admission treated with ACE1 inhibitor and ARB prescriptions (27). The same confirmative conclusions were reached by many others clinical studies (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

COVID-19 and Hypertension: The What, the Why, and the How

“…The susceptibility of hypertensive patients to severe COVID-19 outcome and the fact that SARS-CoV-2 uses ACE2 to enter the cells raised a question regarding the possibility of RAS components modification by antihypertensive agents, with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) being in the center of interest ( Wang et al, 2020c ). ACEi effectively inhibits ACE activity without affecting Ang II binding to AT 1 R. Upon ACE inhibition, Ang I is unable to be converted into Ang II efficiently, thus less Ang II is available to bind to AT 1 R. Whereas ARBs suppress the binding of Ang II to AT 1 R, thus preventing the harmful effects of Ang II ( Leclézio et al, 2020 ).…”

Fundamental and Advanced Therapies, Vaccine Development against SARS-CoV-2

“…Clinical studies have portrayed hypertension as a risk factor in patients suffering from SARS compared to normotensions. In the treatment of patients with COVID-19 with hypertension, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) has been controversial [ 107 , 108 ]. These therapeutic interventions involve ACE-2, the cellular receptor targeted by SARS-COV-2 for its entry and propagation in host cells [ 109 ].…”

“…Recent studies also speculate that ACEIs/ARBs could prevent viral entry of SARS-CoV-2 by stabilizing ACE-2–AT1R interaction and preventing viral protein–ACE-2 interaction or internalization. The interaction of viral protein with ACE-2 decreases in the proximity of stabilized complexes ACE-2–AT1R [ 108 ].…”