The Interplay between the Immune System, the Renin Angiotensin Aldosterone System (RAAS) and RAAS Inhibitors May Modulate the Outcome of COVID‐19: A Systematic Review

Naveed, Hiba; Elshafeey, Abdallah; Al‐Ali, Dana; Janjua, Emmad; Nauman, Areej; Kawas, Hussam; Kaul, Ridhima; Aldien, Arwa Saed; Elshazly, Mohamed B.; Zakaria, Dalia

Since the discovery of the severe acute respiratory syndrome coronarvirus 2 (SARS‐CoV‐2) numerous research was undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS‐CoV‐2 invasion mechanism and the RAAS receptors, created many debates about the possible consequences of using RAAS modulating drugs including the ACE inhibitors (ACEi) and the Angiotensin II Receptor Blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of COVID‐19 in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. While several studies mainly analyzed the outcomes of the disease, this review aimed at comparing specific blood markers in both groups of COVID‐19 patients in order to gain a better insight into the interaction of ACEi/ARBs with the different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID‐19 patients who used or did not use ACEi/ARBs. Interestingly, six studies reported lower inflammatory markers in COVID‐19 patients who used ACEi/ARBs and ten studies reported better outcomes among the same group. We therefore conclude that the use of ACEi/ARBs may not lead to worse prognosis of COVID‐19 and may even play a protective role against the hyperinflammatory response associated with COVID‐19. This article is protected by copyright. All rights reserved