Repurposed drug studies on the primary prevention of SARS-CoV-2 infection during the pandemic: systematic review and meta-analysis

DOI record: { "DOI": "10.1136/bmjresp-2023-001674", "ISSN": [ "2052-4439" ], "URL": "http://dx.doi.org/10.1136/bmjresp-2023-001674", "abstract": "<jats:sec><jats:title>Objective</jats:title><jats:p>Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Systematic review.</jats:p></jats:sec><jats:sec><jats:title>Eligibility</jats:title><jats:p>Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.</jats:p></jats:sec><jats:sec><jats:title>Data source</jats:title><jats:p>PubMed and Embase (1 January 2020–28 September 2022).</jats:p></jats:sec><jats:sec><jats:title>Risk of bias</jats:title><jats:p>Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.</jats:p></jats:sec><jats:sec><jats:title>Data analysis</jats:title><jats:p>Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I<jats:sup>2</jats:sup>=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I<jats:sup>2</jats:sup>=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.</jats:p></jats:sec><jats:sec><jats:title>PROSPERO registration number</jats:title><jats:p>CRD42021292797.</jats:p></jats:sec>", "alternative-id": [ "10.1136/bmjresp-2023-001674" ], "author": [ { "ORCID": "http://orcid.org/0000-0003-1872-0084", "affiliation": [], "authenticated-orcid": false, "family": "Zhou", "given": "Guiling", "sequence": "first" }, { "affiliation": [], "family": "Verweij", "given": "Stefan", "sequence": "additional" }, { "affiliation": [], "family": "Bijlsma", "given": "Maarten J", "sequence": "additional" }, { "affiliation": [], "family": "de Vos", "given": "Stijn", "sequence": "additional" }, { "affiliation": [], "family": "Oude Rengerink", "given": "Katrien", "sequence": "additional" }, { "affiliation": [], "family": "Pasmooij", "given": "Anna Maria Gerdina", "sequence": "additional" }, { "affiliation": [], "family": "van Baarle", "given": "Debbie", "sequence": "additional" }, { "affiliation": [], "family": "Niesters", "given": "Hubert G M", "sequence": "additional" }, { "affiliation": [], "family": "Mol", "given": "Peter", "sequence": "additional" }, { "affiliation": [], "family": "Vonk", "given": "Judith M", "sequence": "additional" }, { "affiliation": [], "family": "Hak", "given": "Eelko", "sequence": "additional" } ], "container-title": "BMJ Open Respiratory Research", "container-title-short": "BMJ Open Resp Res", "content-domain": { "crossmark-restriction": true, "domain": [ "bmj.com" ] }, "created": { "date-parts": [ [ 2023, 8, 28 ] ], "date-time": "2023-08-28T16:50:35Z", "timestamp": 1693241435000 }, "deposited": { "date-parts": [ [ 2023, 8, 28 ] ], "date-time": "2023-08-28T16:50:55Z", "timestamp": 1693241455000 }, "funder": [ { "DOI": "10.13039/501100004543", "award": [ "202107720033" ], "doi-asserted-by": "crossref", "name": "China Scholarship Council" } ], "indexed": { "date-parts": [ [ 2023, 8, 29 ] ], "date-time": "2023-08-29T04:20:20Z", "timestamp": 1693282820001 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2023, 8 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2023, 8, 28 ] ] }, "published-print": { "date-parts": [ [ 2023, 8 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by-nc/4.0/", "content-version": "unspecified", "delay-in-days": 27, "start": { "date-parts": [ [ 2023, 8, 28 ] ], "date-time": "2023-08-28T00:00:00Z", "timestamp": 1693180800000 } } ], "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1136/bmjresp-2023-001674", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "239", "original-title": [], "page": "e001674", "prefix": "10.1136", "published": { "date-parts": [ [ 2023, 8 ] ] }, "published-online": { "date-parts": [ [ 2023, 8, 28 ] ] }, "published-print": { "date-parts": [ [ 2023, 8 ] ] }, "publisher": "BMJ", "reference": [ { "key": "2023082809501442000_10.1.e001674.1", "unstructured": "Johns Hopkins University CSSE COVID-19 data. 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