The role of renin-angiotensin system activated phagocytes in the SARS-CoV-2 coronavirus infection

Objective: Management of the pandemic caused by the novel coronavirus SARS-CoV-2 challenges both scientists and physicians to rapidly develop, and urgently assess, effective diagnostic tests and therapeutic interventions. The initial presentation of the disease in symptomatic patients is invariably respiratory, with dry cough being the main symptom, but an increasing number of reports reveal multiple-organ involvement. The aim of this review is to summarize the potential role of the renin-angiotensin system activated phagocytes in the pathogenesis of COVID-19 disease. Methods: Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “SARS,” “COVID-19,” “renin-angiotensin-system,” “phagocyte,” “reactive free radical,” “antioxidant,” “ARDS,” “thrombosis,” “myocardial,” “ischaemia,” “reperfusion,” “microvascular,” and “ACE2.” Abstracts and reports from meetings were not included in this work. Only articles published in English between 1976 and 2020 were reviewed. Results: The cellular target of SARS viruses is the angiotensin-converting enzyme 2, a critical regulating protein in the renin-angiotensin system. The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst. In the case of an overstimulated host immune response, not only devastating respiratory symptoms but even systemic or multiorgan involvement may be observed. Conclusions: Early-stage medical interventions may assist in returning the exaggerated immune response to a normal range; however, some therapeutic delay might result in excessive tissue damages, occasionally mimicking a systemic disease with a detrimental outcome.