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

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Abstract
Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), numerous research has been 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 renin‐angiotensin‐aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS‐modulating drugs including angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID‐19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID‐19 patients to gain better insight into the interaction of ACEi/ARBs with 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, 6 studies reported lower inflammatory markers in COVID‐19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded 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.

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