Colchicine use in patients with COVID-19: A systematic review and meta-analysis

  1. Leonard Chiu
  2. Chun-Han Lo
  3. Max Shen
  4. Nicholas Chiu
  5. Rahul Aggarwal
  6. Jihui Lee
  7. Young-Geun Choi
  8. Henry Lam
  9. Elizabeth Horn Prsic
  10. Ronald Chow
  11. Hyun Joon Shin

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Abstract

Colchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.

Methods

The literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.

Results

Eight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality—HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not–OR of 0.26 (95% CI: 0.06, 1.09).

Conclusion

Colchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care.

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  1. Version published to 10.1371/journal.pone.0261358
  2. Version published to 10.1101/2021.02.02.21250960v4 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.02.02.21250960: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationRisk of Bias Assessment: Risk of bias was assessed using tools developed by the Cochrane Bias Methods Group, with the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool used for the observational studies and a revised Cochrane risk of bias tool for randomized trials (RoB 2 tool) used for randomized controlled trials (21, 22).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableStudy demographics (i.e. central measure of tendency for age, percentage male) were also noted for each included study.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: The databases of Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials medRxiv, and researchsquare.com were searched from January 2019 through January 28, 2021.
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    Risk of Bias Assessment: Risk of bias was assessed using tools developed by the Cochrane Bias Methods Group, with the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool used for the observational studies and a revised Cochrane risk of bias tool for randomized trials (RoB 2 tool) used for randomized controlled trials (21, 22).
    Cochrane Bias
    suggested: (Robot Reviewer, RRID:SCR_018961)

    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:
    This study is not without limitations. Intrinsic to meta-analysis study designs, the strength of meta-analysis conclusions is limited to the strength of the input studies and underlying data. This meta-analysis contains a mix of observational and RCT data. To reduce bias in grouping observational and RCT, studies were grouped by trial design when comparing mortality in colchicine and non-colchicine users and only studies reporting adjusted risk estimate were used in observational studies. Additionally, all included studies had some concern for risk of bias. Moreover, this review only contains six studies with only two studies examining the risk of ICU admission and two evaluated the risk of mechanical ventilation. Furthermore, the individual risk estimates in the three RCTs often showed values that suggested a direction toward benefit but underpowered to detect a statistically significant mortality benefit; the paucity of RCT data made for further subgroup analysis difficult. To mitigate this, we conducted a sensitivity analysis of the RCTs containing hospitalized patients, which yielded results comparable to those found by Tardif et al in non-hospitalized patients. Further RCTs in every setting of disease care should be studied: including pre-hospitalization, during hospitalization, and during ICU admissions. Furthermore, the long-term effects of COVID-19 are a significant clinical concern and a major source of disability and health care utilization. Further studies in post-...

    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 10.1101/2021.02.02.21250960v3 on medRxiv
  5. Version published to 10.1101/2021.02.02.21250960v2 on medRxiv
  6. Version published to 10.1101/2021.02.02.21250960v1 on medRxiv