{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:54:21Z","timestamp":1790470461323,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Rationale:<\/jats:bold> SARS-CoV-2 gains entrance to airway epithelial cells (AECs) through binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) on the cell surface. However, ACE2 also converts angiotensin II into angiotensin-(1-7) and counterbalances the renin-angiotensin-aldosterone system, with resultant protective effects in the cardiovascular system. Some data suggest that two common antihypertension medications (angiotensin II receptor antagonists, ARBs; and angiotensin-converting-enzyme inhibitors, ACEIs) may increase ACE2 expression in heart and kidney cells, fueling debate about how these widely used medications may modulate SARS-CoV-2 infectivity and risk of COVID-19.<\/jats:p><jats:p><jats:bold>Aim:<\/jats:bold> Determine whether exposure of bronchial AECs to the ARB losartan or the ACEI captopril modulate expression of ACE2 by AECs, SARS CoV2 replication, or expression of proinflammatory cytokines and type I and III interferon (IFN) responses.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Primary bronchial AECs from children and adults (<jats:italic>n<\/jats:italic> = 19; Ages 8\u201375\u00a0yrs) were differentiated <jats:italic>ex vivo<\/jats:italic> at an air-liquid interface to generate organotypic cultures. Cultures were treated with captopril (1\u00a0\u03bcM) or losartan (2\u00a0\u03bcM) with culture media changes starting 72\u00a0h before infection with SARS-CoV-2. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 isolate USA-WA1\/2020 at a multiplicity of infection (MOI) of 0.5. At 96\u00a0h following infection, RNA and protein were isolated. SARS-CoV-2 replication in cultures was assessed with quantitative PCR (qPCR). <jats:italic>ACE2, IL-6, IL-1B, IFNB1<\/jats:italic>, and <jats:italic>IFNL2<\/jats:italic> expression were assessed by qPCR.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Neither captopril nor losartan treatment significantly changed <jats:italic>ACE2, IL-6, IL-1B, IFNB1<\/jats:italic>, or <jats:italic>IFNL2<\/jats:italic> expression by AECs as compared to SARS-CoV-2 infected AEC cultures without captopril or losartan treatment. At 96\u00a0h following infection, SARS-CoV-2 copy number\/ng RNA was not significantly different between untreated AEC cultures, cultures treated with captopril, or cultures treated with losartan.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> These findings suggest that at the level of the airway epithelium neither the ACEI captopril or ARB losartan significantly modify expression of the SARS-CoV-2 entry factor ACE2, nor does either medication increase replication SARS-CoV-2 replication. This <jats:italic>ex vivo<\/jats:italic> data is reassuring and is consistent with evolving clinical data suggesting ACEIs and ARBs do not increase the risk for poor prognosis with COVID-19 and may actually reduce the risk of COVID-19 disease.<\/jats:p>","DOI":"10.3389\/fphar.2021.765951","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T07:51:18Z","timestamp":1637308278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Angiotensin-Converting-Enzyme Inhibitor and Angiotensin II Receptor Antagonist Treatment on ACE2 Expression and SARS-CoV-2 Replication in Primary Airway Epithelial Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Oghenemega","family":"Okoloko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Vanderwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille M.","family":"Rich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney E.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn A.","family":"Barrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Debley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.jaci.2017.10.004","article-title":"Interferon Response to Respiratory Syncytial Virus by Bronchial Epithelium from Children with Asthma is Inversely Correlated with Pulmonary Function","volume":"142","author":"Altman","year":"2017","journal-title":"J. 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