Remdesivir for the treatment of patients hospitalized with COVID-19 receiving supplemental oxygen: a targeted literature review and meta-analysis

  1. Rachel Beckerman
  2. Andrea Gori
  3. Sushanth Jeyakumar
  4. Jakob J. Malin
  5. Roger Paredes
  6. Pedro Póvoa
  7. Nathaniel J. Smith
  8. Armando Teixeira-Pinto

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Abstract

This network meta-analysis (NMA) assessed the efficacy of remdesivir in hospitalized patients with COVID-19 requiring supplemental oxygen. Randomized controlled trials of hospitalized patients with COVID-19, where patients were receiving supplemental oxygen at baseline and at least one arm received treatment with remdesivir, were identified. Outcomes included mortality, recovery, and no longer requiring supplemental oxygen. NMAs were performed for low-flow oxygen (LFO 2 ); high-flow oxygen (HFO 2 ), including NIV (non-invasive ventilation); or oxygen at any flow (AnyO 2 ) at early (day 14/15) and late (day 28/29) time points. Six studies were included (N = 5245 patients) in the NMA. Remdesivir lowered early and late mortality among AnyO 2 patients (risk ratio (RR) 0.52, 95% credible interval (CrI) 0.34–0.79; RR 0.81, 95%CrI 0.69–0.95) and LFO 2 patients (RR 0.21, 95%CrI 0.09–0.46; RR 0.24, 95%CrI 0.11–0.48); no improvement was observed among HFO 2 patients. Improved early and late recovery was observed among LFO 2 patients (RR 1.22, 95%CrI 1.09–1.38; RR 1.17, 95%CrI 1.09–1.28). Remdesivir also lowered the requirement for oxygen support among all patient subgroups. Among hospitalized patients with COVID-19 requiring supplemental oxygen at baseline, use of remdesivir compared to best supportive care is likely to improve the risk of mortality, recovery and need for oxygen support in AnyO 2 and LFO 2 patients.

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  1. Version published to 10.1038/s41598-022-13680-6
  2. ScreenIT

    SciScore for 10.1101/2022.03.04.22271706: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationInclusion criteria for studies were randomized controlled trials (either published or in pre-print) that enrolled patients hospitalized requiring supplemental oxygen at baseline.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy and Inclusion Criteria: A targeted search was conducted over three months (February to April, 2021) to identify relevant materials in MEDLINE (PubMed), medRxiv, EMBASE and Cochrane Trials (Table S2, Supplementary Materials).
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Trials
    suggested: None
    All data analyses were performed using Microsoft Excel (2019) and the R statistical package.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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:
    However, the evaluation and synthesis of evidence in a rapidly evolving field is inherently associated with limitations. First, SIMPLE-Severe could not connect to a network in the base case analysis as it compared 5-versus 10-day treatments of remdesivir (with no further control arm)25; however, a scenario analysis where it was included through its historical control did not meaningfully impact the results. Second, the heterogeneity of the included trials may limit the generalizability of the results. For example, SOLIDARITY did not require all patients to have a confirmed infection of COVID-19, and the inclusion of patients was left at the discretion of the enrolling physician; further, the protocol exclusion criteria were ambiguous. For reasons unknown, mortality rates observed in SOLIDARITY’s best supportive care arm were higher than those observed across other studies conducted in a similar time period. Given SOLIDARITY’s large sample size, these limitations may contribute disproportionately to the results of this analysis. Third, this meta-analysis excludes the recent results of the ACTT-345 and the DisCoVeRy trial46, both of which were published after our search. While ACTT-3 showed similar effects to studies included in this meta-anlsysis of remdesivir alone on mortality rates, DisCoVeRy was a sub-study of SOLIDARITY and the DisCoVeRy trial would have been excluded to avoid potential bias due to double-counting patients. Fourth, across our included trials, the definiti...

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.03.04.22271706 on medRxiv