Abstract
Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.
Highlights
The current COVID-19 pandemic has already made 2,974,642 deaths globally, as reported by the World Health Organization (WHO) on 16th April 2021 [1]
The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity
An important study conducted on a cohort of Veterans with a history of hypertension treated with ACEI/ARB for at least two years or with other types of medications has found that ACEI use was, significantly associated with a lower risk of a positive SARSCoV-2 test compared to non-users and ARB users
Summary
The current COVID-19 pandemic has already made 2,974,642 deaths globally, as reported by the World Health Organization (WHO) on 16th April 2021 [1]. Other studies have not described a direct beneficial effect regarding RAAS inhibitors' use They reported no significant association between using this type of medication and increased susceptibility to SARS-CoV-2 infection or worse patient outcomes, arguing against ACEI/ARB discontinuation [11, 36, 37]. No clinical studies reporting a significantly detrimental result of RAAS inhibitors in COVID-10 patients associating cardiovascular comorbidities could be found in the existing literature Most of these studies' results are contrary to what was previously suspected, and the real mechanism by which these medications intervene in SARS-CoV-2 infection is only partially understood. The increase in the angiotensin II levels will have a negative impact on the overall course of the disease [48] In this regard, as ACEI/ARB leads to an upregulation of ACE2 expression [12], their final effect might be beneficial, contrary to what was originally suspected
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