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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Cardiovasc+Pharmacol 2020 ; 76 (4): 397-406 Nephropedia Template TP
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The Controversy of Renin-Angiotensin-System Blocker Facilitation Versus Countering COVID-19 Infection #MMPMID32769760
Manolis AS; Manolis TA; Manolis AA; Melita H
J Cardiovasc Pharmacol 2020[Oct]; 76 (4): 397-406 PMID32769760show ga
The ongoing COVID-19 pandemic has produced serious turmoil world-wide. Lung injury causing acute respiratory distress syndrome seems to be a most dreaded complication occurring in approximately 30%. Older patients with cardiovascular comorbidities and acute respiratory distress syndrome have an increased mortality. Although the precise mechanisms involved in the development of lung injury have not been fully elucidated, the role of the extended renin-angiotensin system seems to be pivotal. In this context, angiotensin-converting enzyme 2 (ACE2), an angiotensin-converting enzyme homologue, has been recognized as a facilitator of viral entry into the host, albeit its involvement in other counter-regulatory effects, such as converting angiotensin (Ang) II into Ang 1-7 with its known protective actions. Thus, concern was raised that the use of renin-angiotensin system inhibitors by increasing ACE2 expression may enhance patient susceptibility to the COVID-19 virus. However, current data have appeased such concerns because there has been no clinical evidence of a harmful effect of these agents as based on observational studies. However, properly designed future studies will be needed to further confirm or refute current evidence. Furthermore, other pathways may also play important roles in COVID-19 transmission and pathogenesis; spike (S) protein proteases facilitate viral transmission by cleaving S protein that promotes viral entry into the host; neprilysin (NEP), a neutral endopeptidase known to cleave natriuretic peptides, degrades Ang I into Ang 1-7; NEP can also catabolize bradykinin and thus mitigate bradykinin's role in inflammation, whereas, in the same context, specific bradykinin inhibitors may also negate bradykinin's harmful effects. Based on these intricate mechanisms, various preventive and therapeutic strategies may be devised, such as upregulating ACE2 and/or using recombinant ACE2, and exploiting the NEP, bradykinin and serine protease pathways, in addition to anti-inflammatory and antiviral therapies. These issues are herein reviewed, available studies are tabulated and pathogenetic mechanisms are pictorially illustrated.