Addition of Tocilizumab to the Standard of Care Reduces Mortality in Severe COVID-19: A Systematic Review and Meta-Analysis

  1. Umesha Boregowda
  2. Abhilash Perisetti
  3. Arpitha Nanjappa
  4. Mahesh Gajendran
  5. Gurusaravanan Kutti Sridharan
  6. Hemant Goyal

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Abstract

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  1. Version published to 10.3389/fmed.2020.586221
  2. Version published to 10.1101/2020.07.10.20150680v3 on medRxiv
  3. Version published to 10.1101/2020.07.10.20150680v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2020.07.10.20150680: (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 variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Search words ‘Tocilizumab,’ ‘anti-interleukin-6 antibody,’ and ‘COVID-19’ or ‘coronavirus 2019’ in various combinations.
    ‘anti-interleukin-6
    suggested: None
    Software and Algorithms
    SentencesResources
    24] Definitions: Patients, intervention, comparison, and outcomes (PICO) questions: Patients: Patients admitted to hospitals with a confirmed diagnosis of COVID-19 Intervention: Evaluation of TCZ in the treatment of severe COVID-19 Comparison: TCZ and SOC in the treatment of severe COVID-19 Outcome: Reduction in all-cause mortality Search strategy: An electronic database literature search for studies that compared ‘TCZ and SOC’ for the treatment of COVID-19 was performed on PubMed, Embase
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    , Cochrane library, Web of Science, and MedRxiv for articles published from December 2019 till June 14th’ 2020.
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Statistical analysis: The data extracted from studies found on online databases, including PubMed, Embase,
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Statistical analysis was done using Review Manager (Version 5.3; The Nordic Cochrane Centre, Copenhagen, Denmark) and STATA 14.2 (
    STATA
    suggested: (Stata, RRID:SCR_012763)
    StataCorp
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Our study has a few limitations that need to be noted; most of the included studies are retrospective observational studies with only three prospective studies. Most of the included studies were from Italy and the United States. Therefore, the results may not be generalizable. The risk of selection bias is high since most studies did not report whether patients included in the study were consecutive. We were unable to estimate the effect of resource shortage on the mortality, since there was a reported shortage of intensive care units to provide appropriate care for severe COVID-19 patients in Italy. Some of the severe COVID-19 patients were treated in the general ward. Mortality can be significantly affected by comorbidities, which is not evaluated in our meta-analysis. This may have played a role in patient mortality and, therefore, might have affected the outcomes. It should be noted that the administration of antiviral agents was not uniform, and not all pateints received the same antiviral agents in either TCZ group or SOC group. Therefore, the findings of this meta-analysis needs to be validated in well designed randomized clinical trials. Also, we were unable to determine which patients would benefit from TCZ and which patients do not. Lastly, pooled analysis of studies with substantial heterogeneity is debatable. Large RCTs with sufficient power to evaluate the effectiveness of TCZ in the treatment of COVID-19 are needed. Also, there appears to be a role for steroids ...

    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.

  5. Version published to 10.1101/2020.07.10.20150680v1 on medRxiv