Systematic review and meta‐analysis of effectiveness of treatment options against SARS‐CoV‐2 infection

  1. Viveksandeep Thoguluva Chandrasekar
  2. Bhanuprasad Venkatesalu
  3. Harsh K. Patel
  4. Marco Spadaccini
  5. Jacob Manteuffel
  6. Mayur Ramesh

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Abstract

Treatment options for severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2) are limited with no clarity on efficacy and safety profiles. We performed a systematic review and meta‐analysis of studies on patients ≥18 years reporting data on therapeutic interventions in SARS‐CoV‐2. Primary outcome was all‐cause mortality and secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, and progression to severe disease. Pooled rates and odds ratios (OR) were calculated. Twenty‐nine studies with 5207 patients were included. Pooled all‐cause mortality in intervention arm was 12.8% (95% confidence interval [CI]: 8.1%‐17.4%). Mortality was significantly higher for studies using hydroxychloroquine (HCQ) for intervention (OR: 1.36; 95% CI: 0.97‐1.89). Adverse events were also higher in HCQ subgroup (OR: 3.88; 95% CI: 1.60‐9.45). There was no difference in other secondary outcomes. There is a need for well‐designed randomized clinical trials for further investigation of every therapeutic intervention for further insight into different therapeutic options.

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  1. Version published to 10.1002/jmv.26302
  2. ScreenIT

    SciScore for 10.1101/2020.05.20.20108365: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Institutional review board approval was not required for this study since no patient identifiers were disclosed.
    RandomizationEligibility criteria: The inclusion criteria were as follows: 1) Studies reporting outcomes for treatment in SARS-CoV-2 infection 2) All studies including randomized controlled trials (RCTs), prospective, retrospective and case series 3) Full length studies 4) Patients more than 18 years of age.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data sources: A systematic electronic search was performed in PubMed/MEDLINE, Embase, Cochrane Central, Google Scholar, MedRxiv databases to identify published and pre-published studies reporting outcomes related to interventions for SARS-CoV-2 infection, from December 1, 2019 to May 11, 2020.
    PubMed/MEDLINE
    suggested: None
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Central
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    MedRxiv
    suggested: (medRxiv, RRID:SCR_018222)

    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:
    There have been questions raised about the NIH study due to limitations such as change in the primary endpoint of study after initiation of the trial, lack of mortality benefit; study in moderate disease patients who tend to recover spontaneously by the end of second week(38).There are ethical concerns among the scientific community that drugs without proven mortality benefit or reduction in the need for ventilatory support may be promoted in view of aggressive pharmaceutical lobbying. The current pandemic rings echo bells of the 2009 H1N1 pandemic and the desperate stockpiling of oseltamivir, whose proclaimed efficacy was claimed to be a byproduct of concealed information and aggressive lobbying by pharmaceutical companies(39) The published or preprint data for other drugs like Favipravir, Baloxavir/ Marboxil, corticosteroids, convalescent plasma is currently insufficient to make any specific recommendation and our meta-analysis also suggests the same. Our meta-analysis shows that none of the so far studied interventions have a tangible benefit to change the course of disease outcomes with the current published evidence. The clinical studies that compare various interventions like the World health organization (WHO) sponsored solidarity trial that compares Remdesivir, chloroquine or hydroxychloroquine, lopinavir plus ritonavir, and interferon-beta with control arm and has all-cause mortality as the primary outcome is the need of the hour and the results are eagerly awaited(4...

    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.

  3. Version published to 10.1101/2020.05.20.20108365v1 on medRxiv