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This study assessed the extent of bias in that research and reevaluated RAAS inhibitor\u2014COVID\u201019 associations in studies without critical risk of bias.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and\/or severe COVID\u201019 outcomes between those using or not using RAAS inhibitors (ie, angiotensin\u2010converting enzyme inhibitors or angiotensin II type\u2010I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed\u2010effects meta\u2010analyses, only from studies without critical risk of bias that assessed severe COVID\u201019 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta\u2010analysis. In 1\u00a0351\u00a0633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin\u2010converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66\u20130.87;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001; angiotensin II type\u2010I receptor blockers: HR, 0.86; 95% CI, 0.77\u20130.97;\n              <jats:italic>P<\/jats:italic>\n              =0.015) and intubation or death (angiotensin\u2010converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48\u20130.85;\n              <jats:italic>P<\/jats:italic>\n              =0.002; angiotensin II type\u2010I receptor blockers: HR, 0.74; 95% CI, 0.58\u20130.95;\n              <jats:italic>P<\/jats:italic>\n              =0.019) with COVID\u201019 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">This study reveals the critical risk of bias that exists across almost an entire body of COVID\u201019 research, raising an important question: Were research methods and\/or peer\u2010review processes temporarily weakened during the surge of COVID\u201019 research or is this lack of rigor a systemic problem that also exists outside pandemic\u2010based research?<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.crd.york.ac.uk\/prospero\/\">www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n              ; Unique identifier: CRD42021237859.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025289","type":"journal-article","created":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T02:22:13Z","timestamp":1653704533000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Renin\u2010Angiotensin Aldosterone System Inhibitors and COVID\u201019: A Systematic Review and Meta\u2010Analysis Revealing Critical Bias Across a Body of Observational Research"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-7478","authenticated-orcid":false,"given":"Jordan","family":"Loader","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Uppsala University Uppsala Sweden"},{"name":"Inserm U1300 \u2013 HP2 CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute Melbourne Victoria Australia"},{"name":"Mary MacKillop Institute for Health Research, Australian Catholic University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lampa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8454","authenticated-orcid":false,"given":"Johan","family":"Sundstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University Uppsala Sweden"},{"name":"The George Institute for Global Health University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0413-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.510461"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000124667.34652.1a"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/medethics-2020-106494"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19478-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare9020127"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2021.04.005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.3594"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-020-00880-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13246"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002784"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06088-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84678-9"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.11622\/smedj.2020159"},{"key":"e_1_3_2_17_2","article-title":"Angiotensin\u2010converting enzyme inhibitors and angiotensin\u2010receptor blockers and the risk of COVID\u201019 infection or severe disease: systematic review and meta\u2010analysis","volume":"31","author":"Caldeira D","year":"2020","unstructured":"Caldeira D, Alves M, Gouveia e Melo R, Silv\u00e9rio Ant\u00f3nio P, Cunha N, Nunes\u2010Ferreira A, Prada L, Costa J, Pinto FJ. 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