Kaohsiung J Med Sci Two Hits to the Renin-Angiotensin System May Play a Key Role in Severe COVID-19

[tetano]

Kaohsiung J Med Sci


. 2020 Jun 3.
doi: 10.1002/kjm2.12237. Online ahead of print.
Two Hits to the Renin-Angiotensin System May Play a Key Role in Severe COVID-19


Yu-Hsin Tseng ¹ , Rei-Cheng Yang ^{1 2} , Tzong-Shi Lu ³



Affiliations

• PMID: 32492292
• DOI: 10.1002/kjm2.12237

Abstract

The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID-19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID-19 who have comorbidities and may serve as a therapeutic target for COVID-19 treatment.

Keywords: coronavirus disease 2019; renin-angiotensin system); two hits.