Efficacy and harms of remdesivir for the treatment of COVID-19: A systematic review and meta-analysis

  1. Alejandro Piscoya
  2. Luis F. Ng-Sueng
  3. Angela Parra del Riego
  4. Renato Cerna-Viacava
  5. Vinay Pasupuleti
  6. Yuani M. Roman
  7. Priyaleela Thota
  8. C. Michael White
  9. Adrian V. Hernandez

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Abstract

Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.

Methods

Studies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.

Results

We included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I 2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I 2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.

Conclusions

There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.

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  1. Version published to 10.1371/journal.pone.0243705
  2. ScreenIT

    SciScore for 10.1101/2020.05.26.20109595: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableExtracted information included: study authors, year of publication, study design, number of patients, country where study was conducted, median age, proportion of males, comorbidities (obesity, hypertension, diabetes, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease), PCR method for COVID-19 diagnosis, remdesivir dose and duration, control dose and duration, concomitant treatments for both arms, primary outcomes per arm, and secondary outcomes per arm.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, Embase and the Cochrane Library.
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    The PubMed strategy is included in the Supplement.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Assessment of risk of bias: Assessment of risk of bias was performed independently by two investigators (VP, AVH) using the Cochrane RoB 2.0 tool8 for RCTs, and ROBINS-I tool9 for cohort studies with a third reviewer (AP) resolving discrepancies when needed.
    Cochrane RoB
    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: 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04252664SuspendedA Trial of Remdesivir in Adults With Mild and Moderate COVID…

    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 10.1101/2020.05.26.20109595 on medRxiv