COVID-19: a hypothesis regarding the ventilation-perfusion mismatch
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EDITORIAL
Open Access
COVID-19: a hypothesis regarding the ventilation-perfusion mismatch Mario G. Santamarina1,2, Dominique Boisier3, Roberto Contreras4, Martiniano Baque5, Mariano Volpacchio6 and Ignacio Beddings7*
Keywords: COVID-19, Coronavirus, Angiotensin converting enzyme 2, Angiotensin II, Vasoconstriction, Vasoplegia, Ventilation-perfusion ratio
Manuscript In December 2019, a novel human coronavirus, SARSCoV-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 [1]. 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 [2]. 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 [3]. 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 * Correspondence: [email protected] 7 Radiology Department, Clínica Bupa Santiago, Av. Departamental 1455, La Florida, Santiago, Región Metropolitana, Chile Full list of author information is available at the end of the article
injury and respiratory distress [4]. Decreased activity of ACE2 leads to heightened and relatively unopposed vasoconstriction, pro-coagulation, pro-inflammatory, and pro-oxidant angiotensin II effects [5, 6]. In the alveoli, active replication and release of the virus cause the host cell to undergo pyroptosis, a highly inflammatory form of programmed cell death, releasing damageassociated molecules. These are recognized by epithelial cells, endothelial cells, and alveolar macrophages, triggering the generation of pro-inflammatory cytokines and chemokines, which attract monocytes, macrophages, and T cells to the site of infection, promoting further inflammation and establishing a pro-inflammatory feedback loop. Furthermore, pyroptosis of epithelial and endothelial cells damages the alveolar-capillary barrier, resulting in vascular leakage and alveolar edema [1, 7]. The accumulation of fluid, debris, and inflammatory cells in the damaged lung parenchyma results in the appearance of ground-glass opacities, consolidation, and septal thickening in classic imaging modalities. A defective immune re
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