{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:55:54Z","timestamp":1768636554458,"version":"3.49.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neth Heart J"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There has been debate on the use of angiotensin-converting enzyme\u20112 (ACE2) expression mediating pharmacotherapy in COVID-19 infected patients. Although it has been suggested that these drugs might lead to a\u00a0higher susceptibility and severity of COVID-19 infection, experimental data suggest these agents may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A\u00a0systematic literature search was performed to answer the question: What is the effect of medications that influence ACE2 expression (ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones) on the outcomes of COVID-19? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 24\u00a0June 2020. After systematic analysis, nine studies were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results were described for two different groups, an overall group in which all users were compared with non-users and a\u00a0group in which only hypertensive patients were included. Within each group a\u00a0distinction was made between results for ACEI\/ARB use, ACEI use, ARB use, NSAID use and thiazolidinedione use. None of the studies demonstrated increased mortality in the two groups. Furthermore, none of the studies showed an effect on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy. However, the level of evidence of all studies varied from \u2018moderate\u2019 to \u2018very low\u2019, according to the GRADE methodology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Analysis of the literature demonstrated that there was insufficient evidence to answer our objective on the effect of ACE2 expression mediating pharmacotherapy on outcome in COVID-19\u00a0patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s12471-021-01573-8","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T11:53:33Z","timestamp":1618574013000},"page":"20-34","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The effects of ACE2 expression mediating pharmacotherapy in COVID-19\u00a0patients"],"prefix":"10.1007","volume":"29","author":[{"given":"R. R. J.","family":"van Kimmenade","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Belfroid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Hoogervorst-Schilp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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Eur Heart\u00a0J. 2020;41:2058\u201366.","journal-title":"Eur Heart J"},{"key":"1573_CR5","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1093\/cid\/ciaa624","volume":"71","author":"SY Jung","year":"2020","unstructured":"Jung SY, Choi JC, You SH, Kim WY. Association of Renin-angiotensin-aldosterone System Inhibitors With Coronavirus Disease 2019 (COVID-19)\u2014Related Outcomes in Korea: A Nationwide Population-based Cohort Study. Clin Infect Dis. 2020;71:2121\u20138.","journal-title":"Clin Infect Dis"},{"key":"1573_CR6","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.recesp.2020.05.030","volume":"74","author":"D L\u00f3pez-Otero","year":"2021","unstructured":"L\u00f3pez-Otero D, L\u00f3pez-Pais J, Cacho-Antonio CE, et al. Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a\u00a0western population. CARDIOVID registry. 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