Drug Development Research · 2020 · 83 citations · 13 references
Veterinary MedicineInfectious DiseasesPharmacotherapyApoptosisInflammationVirologyAcute Respiratory Distress SyndromeInflammatory SignalingPulmonary InflammationRespiratory DiseaseRespiratory InfectionsAlveolar InflammationAngiotensin Ii Receptor BlockersCovid-19-associated Acute Respiratory Distress SyndromeSars-cov-2 InfectionTissue Concentration
In late 2019, a new coronavirus emerged in Wuhan Province, China, causing lung complications similar to those produced by the SARS coronavirus in the 2002-2003 epidemic. This new disease was named COVID-19 and the causative virus SARS-CoV-2. The SARS-CoV-2 virus enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. The S protein-ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro-inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1-7. High levels of angiotensin II on the lung interstitium can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines, establishing a self-powered cascade, leading eventually to ARDS. Recently, Gurwitz proposed the tentative use of agents such as losartan and telmisartan as alternative options for treating COVID-19 patients prior to development of ARDS. In this commentary article, the authors make the case for the election of telmisartan as such alternative on the basis of its pharmacokinetic and pharmacodynamic properties and present an open-label randomized phase II clinical trial for the evaluation of telmisartan in COVID-19 patients (NCT04355936).
13
The Acute Respiratory Distress Syndrome
Lorraine B. Ware, Michael A. Matthay · New England Journal of Medicine · 2000 · 4.7K citations
Medicine, Pathobiology, Pathology +17
Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19
Muthiah Vaduganathan, Orly Vardeny, Thomas Michel et al. · New England Journal of Medicine · 2020 · 2.2K citations · Full text