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Meta-Analysis
. 2023 Aug;10(1):e001674.
doi: 10.1136/bmjresp-2023-001674.

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

Guiling Zhou  1 , Stefan Verweij  2   3 , Maarten J Bijlsma  2 , Stijn de Vos  2 , Katrien Oude Rengerink  3 , Anna Maria Gerdina Pasmooij  3 , Debbie van Baarle  4 , Hubert G M Niesters  5 , Peter Mol  3   6 , Judith M Vonk  7   8 , Eelko Hak  2
Affiliations
Meta-Analysis

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

Guiling Zhou et al. BMJ Open Respir Res. 2023 Aug.

Abstract

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), I2=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), I2=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.

Keywords: COVID-19; respiratory infection.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
PRISMA flow diagram of article selection. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Meta-analysis of the effect of HCQ prophylaxis on laboratory-confirmed SARS-CoV-2 infection in (A) clinical trials; (B) case-control studies; (C) cohort studies. HCQ, hydroxychloroquine; IV, inverse variance; M-H, Mantel-Haenszel.
Figure 3
Figure 3
Meta-analysis of the effect of HCQ prophylaxis on (A) laboratory-confirmed or clinical-confirmed infection; or (B) hospitalisation in clinical trials. HCQ, hydroxychloroquine; M-H, Mantel-Haenszel.
Figure 4
Figure 4
Meta-analysis of the effect of ivermectin prophylaxis on laboratory-confirmed or clinical-confirmed SARS-CoV-2 infection in clinical trials. M-H, Mantel-Haenszel.
Figure 5
Figure 5
Meta-analysis of the effect of prophylaxis on laboratory-confirmed or clinical-confirmed SARS-CoV-2 infection: (A) ACEI, cohort studies; (B) ACEI, case-control studies; (C) ARB, cohort studies; (D) ARB, case-control studies. ACEi, ACE inhibitor; ARB, angiotensin receptor blocker; IV, inverse variance.
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