The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials

  1. Ifan Ali Wafa
  2. Nando Reza Pratama
  3. David Setyo Budi
  4. Henry Sutanto
  5. Alfian Nur Rosyid
  6. Citrawati Dyah Kencono Wungu

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Abstract

Objectives

The use of monoclonal antibody for COVID-19 showed conflicting results in prior studies and its efficacy remains unclear. We aimed to comprehensively determine the efficacy and safety profile of monoclonal antibodies in COVID-19 patients.

Methods

Sixteen RCTs were analyzed using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs.

Results

The pooled effect of monoclonal antibodies demonstrated mortality risk reduction (RR=0.89 (95%CI 0.82-0.96), I 2 =13%, fixed-effect). Individually, tocilizumab reduced mortality risk in severe to critical disease (RR=0.90 (95%CI 0.83-0.97), I 2 =12%, fixed-effect)) and lowered mechanical ventilation requirements (RR=0.76 (95%CI 0.62-0.94), I 2 =42%, random-effects). Moreover, it facilitated hospital discharge (RR=1.07 (95%CI 1.00-1.14), I 2 =60%, random-effects). Meanwhile, bamlanivimab-etesevimab and REGN-COV2 decrease viral load ((SMD=-0.33 (95%CI -0.59 to -0.08); (SMD=-3.39 (95%CI -3.82 to -2.97)). Interestingly, monoclonal antibodies did not improve hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99–1.12), I 2 =71%, random-effects) and they displayed similar safety profile with placebo/standard therapy (RR=1.04 (95%CI 0.76-1.43), I 2 =54%, random-effects).

Conclusion

Tocilizumab improved hospital discharge and reduced mortality as well as the need for mechanical ventilation, while bamlanivimab-etesevimab and REGN-COV2 reduced viral load in mild to moderate outpatients. In general, monoclonal antibodies are safe and should be considered in severe to critical COVID-19 patients.

Registration

PROSPERO (CRD42021235112)

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  1. ScreenIT

    SciScore for 10.1101/2021.06.04.21258343: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableWe independently screened the title and abstract of all retrieved studies based on the following eligibility criteria: (1) participants confirmed at any clinical stage of COVID-19 with/without other comorbidities; (2) adult (≥18 years) male/female study population; (3) the study involved monoclonal antibody treatments of interest; (4) the study compared the intervention group with control (placebo or/and standard of care or combination therapy); (5) the study evaluated efficacy (i.e. mortality, need for mechanical ventilation, hospital discharge, virologic outcomes) or safety outcomes (serious adverse events); (6) study type was randomized controlled trial (RCT).
    RandomizationWe independently screened the title and abstract of all retrieved studies based on the following eligibility criteria: (1) participants confirmed at any clinical stage of COVID-19 with/without other comorbidities; (2) adult (≥18 years) male/female study population; (3) the study involved monoclonal antibody treatments of interest; (4) the study compared the intervention group with control (placebo or/and standard of care or combination therapy); (5) the study evaluated efficacy (i.e. mortality, need for mechanical ventilation, hospital discharge, virologic outcomes) or safety outcomes (serious adverse events); (6) study type was randomized controlled trial (RCT).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: The PubMed (MEDLINE), ScienceDirect, Cochrane Library, Proquest and Springer databases were systematically searched from January 25 until February 5, 2021, without any limitation of publication year.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Proquest
    suggested: (ProQuest, RRID:SCR_006093)
    Data Extraction and Quality Assessment: IAW, NRP, and DSB independently extracted relevant data using the standardized form.
    Quality Assessment
    suggested: (Image and Data Quality Assessment Ontology, RRID:SCR_010343)
    Statistical Analysis: Primary analyses were carried out using the Review Manager version 5.4 (The Cochrane Collaboration).
    Cochrane Collaboration
    suggested: None

    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
    NCT04427501RecruitingA Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) i…

    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.

  2. Version published to 10.1101/2021.06.04.21258343v1 on medRxiv