Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis

  1. Zakariya Kashour
  2. Muhammad Riaz
  3. Musa A Garbati
  4. Oweida AlDosary
  5. Haytham Tlayjeh
  6. Dana Gerberi
  7. M Hassan Murad
  8. M Rizwan Sohail
  9. Tarek Kashour
  10. Imad M Tleyjeh

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Abstract

Objectives

Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients.

Methods

We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization.

Results

Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96–1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00–1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19.

Conclusions

Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.

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  1. Version published to 10.1093/jac/dkaa403
  2. Version published to 10.1101/2020.07.12.20150110v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.07.12.20150110: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationTwo reviewers (ZK and OA) independently assessed risk of bias for each study using the (RoB 2) of the Cochrane risk-of-bias tool for randomized trials [21] and the Newcastle–Ottawa instrument for cohort studies and case–control studies [22].
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In addition, we searched Google Scholar and the references of eligible studies and review articles.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Two reviewers (ZK and OA) independently assessed risk of bias for each study using the (RoB 2) of the Cochrane risk-of-bias tool for randomized trials [21] and the Newcastle–Ottawa instrument for cohort studies and case–control studies [22].
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    All analyses were conducted using Stata version 16 statistical software (StataCorp, College Station, Texas).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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.

  4. Version published to 10.1101/2020.07.12.20150110v1 on medRxiv