Renin–Angiotensin system and fibrinolytic pathway in COVID-19: One-way skepticism

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a recent pandemic infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The entry point of SARS-CoV-2 is via angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the alveolar pulmonary cells. Besides, different peptides and co-mediators such as bradykinin (BK), plasmin, and trans-membrane serine protease may modulate the affinity and binding of SARS-CoV-2 to ACE2. Therefore, this study was planned to review the potential link between the pathogenesis, incidence, and severity of SARS-CoV-2 infection regarding the modulation of ACE2 by these mediators. Electronic database searches of Scopus, Web of Science, Medline, Cochrane Central Register of Controlled Trials, and PubMed was made using MeSH terms, keywords, and title words. Renin–angiotensin system inhibitors might be of value in the reduction of acute respiratory distress syndrome (ARDS), respiratory failure, and acute pneumonia that are induced by SARS-CoV-2. SARS-CoV-2 infection leads to noteworthy lung injury via downregulation of ACE2, which is attenuated by the administration of angiotensin receptor blockers (ARBs). In SARS-CoV-2 infection, BK and its metabolites are augmented due to the downregulation of ACE2 by SARS-CoV-2. SARS-CoV-2 pneumonia is also associated with hyperfibrinolysis as evident with high circulating fibrin degradation products, high plasmin, and presence of hemorrhagic spots in multiple organs. ACEIs improve fibrinolysis via inhibition of PAI-1, while ARBs have a neutral effect on both fibrinolysis and PAI-1. Therefore, these findings show ACEIs but not ARBs as a potential risk for the development of SARS-CoV-2 infection as both plasmin and BK facilitate the pathogenesis of SARS-CoV-2 and augment the development of ARDS in SARS-CoV-2 infection.