Authors: Santamarina MG, Boisier D, Contreras R, Baque M, Volpacchio M
PMID: 32631389 PMCID: PMC7338110 DOI: 10.1186/s13054-020-03125-9
Abstract
In December 2019, a novel human coronavirus, SARS-CoV-2, was detected in the city of Wuhan, China, which since then has expanded throughout the world and caused a pandemic coronavirus disease (COVID-19).
SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) as the functional receptor for cell entry. In contrast to SARS-CoV, SARS-CoV-2 forms more molecular interactions with ACE2, which correlates with data showing a fourfold higher affinity for receptor binding. Subsequently, endocytosis of the viral complex occurs, and surface ACE2 is downregulated. This hampers angiotensin II cleavage, leading to increased circulating angiotensin II and increased angiotensin II receptor activation.
ACE2 is a counterregulatory enzyme that degrades angiotensin II to angiotensin-(1-7). Angiotensin-(1-7) stimulates vasodilatation and nitric oxide production and also attenuates the effects of angiotensin II of vasoconstriction, sodium retention, and fibrosis. A study showed that patients with COVID-19 appeared to have elevated levels of plasma angiotensin II, which were correlated with the degree of lung injury and total viral load. SARS-CoV-2 binding to ACE2 may attenuate ACE2 activity, increasing angiotensin II-mediated pulmonary vasoconstriction, as well as inflammatory and oxidative organ damage, ultimately progressing towards acute lung injury and respiratory distress. Decreased activity of ACE2 leads to heightened and relatively unopposed vasoconstriction, pro-coagulation, pro-inflammatory, and pro-oxidant angiotensin II effects.
Keywords: COVID-19, SARS-CoV-2, ventilation-perfusion mismatch
