Hydroxychloroquine in COVID-19: An updated systematic review with meta-analysis

  1. Jose Chacko
  2. Gagan Brar
  3. Robert Premkumar

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Abstract

Background

Hydroxychloroquine is being administered among patients with COVID-19 infection in many healthcare systems across the world, considering its in vitro effect against the SARS-CoV-2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID-19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID-19 infection.

Methods

We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until August 1, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was administered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity.

Results

We included 23 studies, including seven randomized controlled trials and 16 observational studies. Among these, 11,029 patients received hydroxychloroquine alone or in combination, while 12063 did not. Mortality was reported at different points in time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 0.94, 95% CI: 0.72–1.22; p = 0.63). Clinical worsening did not differ between patients who received hydroxychloroquine compared to those who did not (OR 0.93, 95% CI: 0.57–1.52; p = 0.77). Negative conversion, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 0.67, CI: 0.21–2.11; p = 0.49). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1–6.55; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 5.95, CI: 2.56–13.83; p < 0.00001).

Conclusions

Our meta-analysis does not suggest improvement in mortality, clinical progression, or negative conversion by RT-PCR among patients with COVID-19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.

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  1. Version published to 10.1101/2020.05.14.20101774v3 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.05.14.20101774: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationBoth randomized controlled trials (RCTs) and observational studies with a comparator group were considered for inclusion.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We performed a systematic search of PubMed, Embase, the Cochrane Library, Web of Science, and the medRxiv databases until August 1, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    All analyses were performed using Review Manager 5.3 (RevMan 5.3; The Cochrane Collaboration, Oxford, UK).
    RevMan
    suggested: (RevMan, RRID:SCR_003581)
    Cochrane Collaboration
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.05.14.20101774v2 on medRxiv
  4. Version published to 10.1101/2020.05.14.20101774v1 on medRxiv