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

OBJECTIVE: 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. DESIGN: Systematic review. ELIGIBILITY: 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. DATA SOURCE: PubMed and Embase (1 January 2020–28 September 2022). RISK OF BIAS: 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. DATA ANALYSIS: Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available. RESULTS: 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(2)=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(2)=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. CONCLUSIONS: 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. PROSPERO REGISTRATION NUMBER: CRD42021292797.