Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis

  1. Qianling Shi
  2. Qi Zhou
  3. Xia Wang
  4. Jing Liao
  5. Yang Yu
  6. Zijun Wang
  7. Shuya Lu
  8. Yanfang Ma
  9. Yangqin Xun
  10. Xufei Luo
  11. Weiguo Li
  12. Toshio Fukuoka
  13. Hyeong Sik Ahn
  14. Myeong Soo Lee
  15. Zhengxiu Luo
  16. Enmei Liu
  17. Yaolong Chen
  18. Qubei Li
  19. Kehu Yang
  20. Quanlin Guan

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Abstract

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  1. ScreenIT

    SciScore for 10.1101/2020.04.13.20064436: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationWe included all randomized controlled trials (RCTs), clinical controlled trials (CCTs) and cohort studies that compared the effectiveness and safety of antiviral agents (including but not limited to IFN, oseltamivir, LPV/r, RBV, HCQ and remdesivir) with placebo, or comparing the combination of antiviral agents and symptomatic treatment with symptomatic treatment alone.
    BlindingFor RCTs we used the Cochrane Risk-of-Bias (RoB) assessment tool consisting seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other bias.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: Two researchers (Q Shi and X Wang) searched the following electronic databases from their inception until March 31, 2020: MEDLINE (via PubMed), Embase, Web of Science, the Cochrane library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data.(22) We also searched three clinical trial registry platforms (the WHO Clinical Trials Registry Platform, US National Institutes of Health Trials Register and the International Standard Randomized Controlled Trial Number [ISRCTN] Register), Google Scholar, the official websites of WHO and Centers for Disease Control (CDC), and the preprint platforms BioRxiv, MedRxiv, and SSRN.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    BioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    We systematically searched by combining the MeSH and free words.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    The keywords and terms in the MEDLINE including “COVID-19”, “SARS-CoV-2”, “Novel coronavirus”, “2019-novel coronavirus”, “2019-nCoV”, “antiviral agents”, “antiviral*”, “ribavirin”, “interferon”, “oseltamivir”, “remdesivir”, “lopinavir”, “ritonavir”, “LPV/r” and their derivatives.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    The specific bibliographic software EndNote was used, and discrepancies were discussed, or solved with a third researcher (Q Zhou).
    EndNote
    suggested: (EndNote, RRID:SCR_014001)
    For RCTs we used the Cochrane Risk-of-Bias (RoB) assessment tool consisting seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other bias.
    Cochrane Risk-of-Bias
    suggested: None
    We processed the data according to the Cochrane Handbook by using a random-effects model.
    Cochrane Handbook
    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: We detected the following sentences addressing limitations in the study:
    Strengthens and Limitations: This study is to our knowledge the first systematic and comprehensive rapid review for the effectiveness and safety of antiviral agents in children with COVID-19. It can therefore be considered the best evidence at the moment for the management of COVID-19 in children, and help to respond to the current public health emergency. Our study was also performed and reported in accordance with Cochrane Handbook and PRISMA checklist, and included Meta-analyses and grading of evidence to draw quantitative conclusions with scientific and rigorous methods. However, our study had also some limitations: First, this rapid review was unable to identify direct evidence for antiviral use in children with COVID-19 and only summarized the indirect evidence, mainly from adults patients with COVID-19, SARS or MERS. The reported treatment effects should be interpreted with caution due to the lack of high-quality RCTs and direct evidence. Second, due to the heterogeneity of the reviewed studies in terms of the wide range of treatment dosages, frequencies and routes of administration, we were unable to perform a quantitative analysis from these aspects for each antiviral. This is a major obstacle to a clear interpretation of the results of this review. Third, because of the specificity and urgency of PHEIC, our study protocol was not registered on the Prospective Register of Systematic Reviews Platform. Further Suggestions: We suggest for the further actions on the basi...

    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.

  2. Version published to 10.21037/atm-20-3301
  3. Version published to 10.1101/2020.04.13.20064436 on medRxiv