Chloroquine and Hydroxychloroquine for the Treatment of COVID-19: a Systematic Review and Meta-analysis

  1. Arunmozhimaran Elavarasi
  2. Manya Prasad
  3. Tulika Seth
  4. Ranjit Kumar Sahoo
  5. Karan Madan
  6. Neeraj Nischal
  7. Manish Soneja
  8. Atul Sharma
  9. Subir Kumar Maulik
  10. Shalimar
  11. Pramod Garg

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  1. ScreenIT

    SciScore for 10.1101/2020.07.04.20146381: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationTypes of studies: We included studies on humans, which were randomized controlled trials (RCTs), prospective or retrospective case series or cohort studies with a control arm.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We included indexed studies from PubMed, Google scholar as well as non-indexed and pre-print articles from various pre-print servers because the latest information on COVID-19, a new disease, available on these pre-print servers might be valuable for the present review. 2.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Types of Interventions: We sought studies in which patients were given HCQ or CQ in any dose, alone or combined with other drugs and had compared with patients in whom HCQ or chloroquine was not given. 4. Outcomes: For each study, we sought the following outcomes: Search strategy and Identification of studies: Two authors independently searched the PubMed, Google Scholar and MedRxiv databases using the following search terms: “[(chloroquine OR hydroxychloroquine) AND (COVID-19 OR SARS-CoV-2)]” from 2000 to 8th June 2020.
    MedRxiv
    suggested: (medRxiv, RRID:SCR_018222)
    Data collection and analysis: The citations were retrieved into a reference management software (Zotero version 5.0.85).
    Zotero
    suggested: (Zotero, RRID:SCR_013784)
    All the analyses were performed using RevMan 5.3.
    RevMan
    suggested: (RevMan, RRID:SCR_003581)

    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: We detected the following sentences addressing limitations in the study:
    The initial observational studies and RCTs had many limitations such as small sample size, heterogenous patient population, variable endpoints, variable dosing of the drug, and no control for confounders. Serious adverse drug reactions with the use of CQ and HCQ though uncommon have been reported. These include cardiac toxicity in the form of cardiomyopathy and prolonged QTc interval,[27] and hemolysis in patients with underlying G6PD deficiency. Moreover, their therapeutic index is narrow.[28] The NIH panel has recommended against using high-dose chloroquine (600 mg twice daily for 10 days) and a combination of hydroxychloroquine plus azithromycin because of the potential for toxicities.[29] The most recent and largest study which reported a higher mortality was subsequently retracted due to multiple reasons chiefly lack of access to data for independent review held by a private company.[30] The investigators of a multicenter trial, the RECOVERY trial, being conducted in the UK have announced negative results but the full report is still to be published. Our results are at odds with those of a recent meta-analysis from France which has shown that HCQ results in significant improvements in various clinical parameters including mortality.[31]. However, this meta-analysis did not use the standard methodology for a meta-analysis and did not do a proper risk of bias assessment for the included studies. They also included a study in their meta-analysis which has now been retracted...

    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.

  2. Version published to 10.1007/s11606-020-06146-w
  3. ScreenIT

    SciScore for 10.1101/2020.07.04.20146381: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.RandomizationResults: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care.BlindingThe RCTs were not blinded and fraught with a risk of assessment bias.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We included indexed studies from PubMed , Google scholar as well as non-indexed and pre-print articles from various pre-print servers because the latest information on COVID-19 , a new disease , available on these pre-print servers might be valuable for the present review . 2 .
    Google scholar
    suggested: (Google Scholar, SCR_008878)
    Data collection and analysis The citations were retrieved into a reference management software ( Zotero version 5.0.85) .
    Zotero
    suggested: (Zotero, SCR_013784)
    All the analyses were performed using RevMan 5.3 .
    RevMan
    suggested: (RevMan, SCR_003581)
    [ 6 ] Results: Description of studies The PubMed search yielded 579 articles .
    PubMed
    suggested: (PubMed, SCR_004846)
    MedRxiv search yielded 291 articles and Google scholar search yielded 1360 articles .
    MedRxiv
    suggested: (medRxiv, SCR_018222)

    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 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).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.04.20146381v1 on medRxiv