{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T17:04:56Z","timestamp":1780851896160,"version":"3.54.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["IJC Heart & Vasculature"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.ijcha.2020.100627","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T08:27:29Z","timestamp":1598516849000},"page":"100627","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers and the risk of COVID-19 infection or severe disease: Systematic review and meta-analysis"],"prefix":"10.1016","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-5673","authenticated-orcid":false,"given":"Daniel","family":"Caldeira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Gouveia e Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Silv\u00e9rio Ant\u00f3nio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00e9lson","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afonso","family":"Nunes-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Prada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto J","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ijcha.2020.100627_b0005","unstructured":"WHO. Coronavirus disease 2019 (COVID-19): situation report, vol. 129, 2020."},{"issue":"2","key":"10.1016\/j.ijcha.2020.100627_b0010","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"issue":"4","key":"10.1016\/j.ijcha.2020.100627_b0015","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/S2213-2600(20)30116-8","article-title":"Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?","volume":"8","author":"Fang","year":"2020","journal-title":"Lancet Respiratory Med."},{"key":"10.1016\/j.ijcha.2020.100627_b0020","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA"},{"key":"10.1016\/j.ijcha.2020.100627_b0025","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ (Clinical research ed)"},{"key":"10.1016\/j.ijcha.2020.100627_b0030","unstructured":"Organization WH. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. World Health Organization, 2020."},{"issue":"13","key":"10.1016\/j.ijcha.2020.100627_b0035","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.ijcha.2020.100627_b0040","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ (Clinical research ed)"},{"key":"10.1016\/j.ijcha.2020.100627_b0045","unstructured":"J.P.T. Higgins, D.G. Altman, J.A.C. Sterne, Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 510 (updated March 2011), The Cochrane Collaboration, 2011."},{"issue":"11","key":"10.1016\/j.ijcha.2020.100627_b0050","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Statist. Med."},{"issue":"11","key":"10.1016\/j.ijcha.2020.100627_b0055","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1002\/sim.1188","article-title":"Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes","volume":"21","author":"Deeks","year":"2002","journal-title":"Statist. Med."},{"key":"10.1016\/j.ijcha.2020.100627_b0060","unstructured":"J.A.C.E.M. Sterne, D. Moher, I. Boutron (Eds.), Chapter 10: Addressing reporting biases, Cochrane Handbook for Systematic Reviews of Interventions version 520 (updated June 2017), Cochrane, 2017. Available from: www.training.cochrane.org\/handbook."},{"key":"10.1016\/j.ijcha.2020.100627_b0065","unstructured":"H.J.O.A. Sch\u00fcnemann, J.P.T. Higgins, G.E. Vist, P. Glasziou, E. Akl, G.H. Guyatt, on behalf of the Cochrane GRADEing Methods Group and the Cochrane Statistical Methods Group. Chapter 11: Completing \u2018Summary of findings\u2019 tables and grading the confidence in or quality of the evidence, in: J.P.T.C.R. Higgins, J. Chandler, M.S. Cumpston (Eds.), Cochrane Handbook for Systematic Reviews of Interventions version 520 (updated June 2017), Cochrane; 2017. Available from: www.training.cochrane.org\/handbook."},{"key":"10.1016\/j.ijcha.2020.100627_b0070","doi-asserted-by":"crossref","DOI":"10.1164\/rccm.202002-0445OC","article-title":"COVID-19 with Different Severity: A Multi-center Study of Clinical Features","author":"Feng","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"7","key":"10.1016\/j.ijcha.2020.100627_b0075","doi-asserted-by":"crossref","first-page":"430","DOI":"10.21037\/atm.2020.03.229","article-title":"The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension","volume":"8","author":"Huang","year":"2020","journal-title":"Ann. Transl. Med."},{"issue":"7","key":"10.1016\/j.ijcha.2020.100627_b0080","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1001\/jamacardio.2020.1624","article-title":"Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China","volume":"5","author":"Li","year":"2020","journal-title":"JAMA Cardiol."},{"issue":"25","key":"10.1016\/j.ijcha.2020.100627_b0085","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1056\/NEJMoa2006923","article-title":"Renin\u2013Angiotensin\u2013Aldosterone System Blockers and the Risk of Covid-19","volume":"382","author":"Mancia","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ijcha.2020.100627_b0090","doi-asserted-by":"crossref","DOI":"10.1001\/jamacardio.2020.1855","article-title":"Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)","author":"Mehta","year":"2020","journal-title":"JAMA Cardiol."},{"key":"10.1016\/j.ijcha.2020.100627_b0095","doi-asserted-by":"crossref","DOI":"10.1097\/ACM.0000000000003478","article-title":"Medical Students Are Not Essential Workers: Examining Institutional Responsibility During the COVID-19 Pandemic","author":"Menon","year":"2020","journal-title":"Academic Med.: J. Assoc. American Med. Colleges"},{"issue":"25","key":"10.1016\/j.ijcha.2020.100627_b0100","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1056\/NEJMoa2008975","article-title":"Renin\u2013Angiotensin\u2013Aldosterone System Inhibitors and Risk of Covid-19","volume":"382","author":"Reynolds","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ijcha.2020.100627_b0105","unstructured":"G. Yang, Z. Tan, L. Zhou, M. Yang, L. Peng, J. Liu, et al., Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study, Hypertension (Dallas, Tex : 1979). 2020."},{"key":"10.1016\/j.ijcha.2020.100627_b0110","article-title":"Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19","author":"Zhang","year":"2020","journal-title":"Circ. Res."},{"key":"10.1016\/j.ijcha.2020.100627_b0115","doi-asserted-by":"crossref","unstructured":"S. Tedeschi, M. Giannella, M. Bartoletti, F. Trapani, M. Tadolini, C. Borghi, et al., Clinical impact of renin-angiotensin system inhibitors on in-hospital mortality of patients with hypertension hospitalized for COVID-19, Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2020.","DOI":"10.1093\/cid\/ciaa492"},{"key":"10.1016\/j.ijcha.2020.100627_b0120","doi-asserted-by":"crossref","first-page":"101738","DOI":"10.1016\/j.tmaid.2020.101738","article-title":"Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France","volume":"35","author":"Million","year":"2020","journal-title":"Travel Med. Infect. Dis."},{"key":"10.1016\/j.ijcha.2020.100627_b0125","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/taaa069","article-title":"Angiotension-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection","author":"Chodick","year":"2020","journal-title":"J. Travel Med."},{"issue":"7","key":"10.1016\/j.ijcha.2020.100627_b0130","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1080\/10641963.2020.1764018","article-title":"Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin\u2013angiotensin system inhibitors","volume":"42","author":"Zhou","year":"2020","journal-title":"Clin. Exp. Hypertens."},{"key":"10.1016\/j.ijcha.2020.100627_b0135","unstructured":"F.J. de Abajo, S. Rodriguez-Martin, V. Lerma, G. Mejia-Abril, M. Aguilar, A. Garcia-Luque, et al., Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study, Lancet (London, England), 2020."},{"key":"10.1016\/j.ijcha.2020.100627_b0140","doi-asserted-by":"crossref","unstructured":"R. Gnavi, M. Demaria, R. Picariello, M. Dalmasso, F. Ricceri, G. Costa, Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020.","DOI":"10.1093\/cid\/ciaa634"},{"key":"10.1016\/j.ijcha.2020.100627_b0145","doi-asserted-by":"crossref","unstructured":"S.Y. Jung, J.C. Choi, S.H. You, W.Y. Kim, Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020.","DOI":"10.1093\/cid\/ciaa624"},{"issue":"4","key":"10.1016\/j.ijcha.2020.100627_b0150","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.therap.2020.05.005","article-title":"Pharmacological characteristics of patients infected with SARS-Cov-2 admitted to Intensive Care Unit in South of France","volume":"75","author":"Montastruc","year":"2020","journal-title":"Therapies"},{"key":"10.1016\/j.ijcha.2020.100627_b0155","first-page":"E004","article-title":"Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV","volume":"48","author":"Peng","year":"2020","journal-title":"Zhonghua xin xue guan bing za zhi."},{"key":"10.1016\/j.ijcha.2020.100627_b0160","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2020.05.034","article-title":"Associations Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blocker Use, Gastrointestinal Symptoms, and Mortality Among Patients With COVID-19","author":"Tan","year":"2020","journal-title":"Gastroenterology"},{"issue":"7","key":"10.1016\/j.ijcha.2020.100627_b0165","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2337\/dc20-0660","article-title":"Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication","volume":"43","author":"Chen","year":"2020","journal-title":"Dia Care"},{"key":"10.1016\/j.ijcha.2020.100627_b0170","doi-asserted-by":"crossref","DOI":"10.1002\/ejhf.1924","article-title":"ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust","author":"Bean","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"10.1016\/j.ijcha.2020.100627_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.jacc.2020.05.040","article-title":"Ramipril in High Risk Patients with COVID-19","author":"Amat-Santos","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ijcha.2020.100627_b0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.jinf.2020.05.056","article-title":"COVID-19 patients with hypertension have more severity condition, and ACEI\/ARB treatment have no infulence on the clinical severity and outcome","author":"Hu","year":"2020","journal-title":"J. Infect."},{"key":"10.1016\/j.ijcha.2020.100627_b0185","doi-asserted-by":"crossref","DOI":"10.1111\/joim.13119","article-title":"Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States","author":"Imam","year":"2020","journal-title":"J. Internal Med."},{"key":"10.1016\/j.ijcha.2020.100627_b0190","doi-asserted-by":"crossref","unstructured":"Gao C, Cai Y, Zhang K, Zhou L, Zhang Y, Zhang X, et al. Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. European heart journal. 2020;41:2058-66.","DOI":"10.1093\/eurheartj\/ehaa433"},{"key":"10.1016\/j.ijcha.2020.100627_b0195","doi-asserted-by":"crossref","unstructured":"Felice C, Nardin C, Di Tanna GL, Grossi U, Bernardi E, Scaldaferri L, et al. Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives. American journal of hypertension. 2020.","DOI":"10.1093\/ajh\/hpaa096"},{"key":"10.1016\/j.ijcha.2020.100627_b0200","doi-asserted-by":"crossref","unstructured":"Argenziano MG, Bruce SL, Slater CL, Tiao JR, Baldwin MR, Barr RG, et al. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. 2020;369:m1996.","DOI":"10.1136\/bmj.m1996"},{"key":"10.1016\/j.ijcha.2020.100627_b0205","doi-asserted-by":"crossref","unstructured":"Kreutz R, Algharably EAE, Azizi M, Dobrowolski P, Guzik T, Januszewicz A, et al. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19. Cardiovascular research. 2020.","DOI":"10.1093\/cvr\/cvaa097"},{"issue":"jul11 1","key":"10.1016\/j.ijcha.2020.100627_b0210","doi-asserted-by":"crossref","first-page":"e4260","DOI":"10.1136\/bmj.e4260","article-title":"Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis","volume":"345","author":"Caldeira","year":"2012","journal-title":"BMJ"},{"key":"10.1016\/j.ijcha.2020.100627_b0215","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fmed.2020.00248","article-title":"The Lung, the Heart, the Novel Coronavirus, and the Renin-Angiotensin System; The Need for Clinical Trials","volume":"7","author":"Lumbers","year":"2020","journal-title":"Frontiers in medicine."},{"issue":"7047","key":"10.1016\/j.ijcha.2020.100627_b0220","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.ijcha.2020.100627_b0225","doi-asserted-by":"crossref","first-page":"104350","DOI":"10.1016\/j.yexmp.2019.104350","article-title":"ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway","volume":"113","author":"Ye","year":"2020","journal-title":"Exp. Mol. Pathol."},{"key":"10.1016\/j.ijcha.2020.100627_b0230","doi-asserted-by":"crossref","unstructured":"Sama IE, Ravera A, Santema BT, van Goor H, Ter Maaten JM, Cleland JGF, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. European heart journal. 2020;41:1810-7.","DOI":"10.1093\/eurheartj\/ehaa373"},{"key":"10.1016\/j.ijcha.2020.100627_b0235","doi-asserted-by":"crossref","unstructured":"Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM. Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease. 2018;13:e0198144.","DOI":"10.1371\/journal.pone.0198144"},{"issue":"1","key":"10.1016\/j.ijcha.2020.100627_b0240","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/ajh\/hpu086","article-title":"Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker","volume":"28","author":"Furuhashi","year":"2015","journal-title":"Am. J. Hypertens."},{"issue":"4","key":"10.1016\/j.ijcha.2020.100627_b0245","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1056\/NEJMc2005396","article-title":"Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom","volume":"383","author":"Chung","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["IJC Heart & Vasculature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352906720303250?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352906720303250?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T05:11:11Z","timestamp":1762492271000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352906720303250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":49,"alternative-id":["S2352906720303250"],"URL":"https:\/\/doi.org\/10.1016\/j.ijcha.2020.100627","relation":{},"ISSN":["2352-9067"],"issn-type":[{"value":"2352-9067","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers and the risk of COVID-19 infection or severe disease: Systematic review and meta-analysis","name":"articletitle","label":"Article Title"},{"value":"IJC Heart & Vasculature","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijcha.2020.100627","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"100627"}}