Efficacy of various treatment modalities for nCOV‐2019: A systematic review and meta‐analysis

  1. Shubham Misra
  2. Manabesh Nath
  3. Vijay Hadda
  4. Deepti Vibha

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Abstract

Background

Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV‐2019). We conducted a systematic review and meta‐analysis to assess the efficacy of various treatment modalities in nCOV‐2019 patients.

Methods

A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed‐effect model was applied if I 2  < 50%, else results were combined using random‐effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between‐study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.

Results

Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV‐2019 patients were included. Lopinavir‐ritonavir was significantly associated with shorter mean time to clinical recovery (SMD −0.32; 95% CI −0.57 to −0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all‐cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all‐cause mortality and more total adverse events.

Conclusion

Our meta‐analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV‐2019 patients. Lopinavir‐ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV‐2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.

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  1. Version published to 10.1111/eci.13383
  2. ScreenIT

    SciScore for 10.1101/2020.05.24.20111799: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationOutcome: Inclusion and exclusion criteria: The criteria for the inclusion of studies in our systematic review and meta-analysis was: For inclusion of clinical studies: (1) randomized controlled trials (RCTs), non-RCTs, cohort studies, case-control studies; (2) studies should be focused on various treatments given to nCOV-2019 patients; (3) studies must have a comparator group comparing the primary treatment drug to either standard care/control or placebo or a second treatment drug; (4) conducted on human subjects only.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Electronic search: Electronic databases including, PubMed, EMBASE, Medline, Google Scholar, Cochrane library and clinicaltrials.gov were searched independently by two authors (SM and MN) till 22 May 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)
    The following MeSH terms or free text terms were used: “2019 novel coronavirus”, “2019 nCOV”, “COVID19’’, “SARS-CoV-2”, “drug therapy”, “vaccine”, “anti-viral therapy”, “symptomatic treatment”, “preventive therapy”, “immunotherapy”.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)

    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:
    Limitations: Although we made sure that our systematic review and meta-analysis was conducted very comprehensively, certain inherent and obvious limitations cannot be ignored. Firstly, due to the limited number of studies, our meta-analysis pooled the data from RCTs and non-RCTs/cohort/case-control studies together which is generally not advisable. However, we did conduct a subgroup analysis based on study design wherever possible to separate the RCTs from non-RCTs/cohort/case-control studies. Secondly, all outcome measures could not be assessed for all the potential treatments due to scarcity of literature. Thirdly, a significant amount of studies included in the review were in their preprint versions and yet to be peer reviewed by experts. Lastly, since several clinical trials on nCQV-2019 treatments are currently ongoing, the results of our meta-analysis might change significantly owing to the findings published in near future. Nonetheless, our meta-analysis presents preliminary evidence of benefit/harm of the possible treatments being administered to nCOV-2019 patients and these preliminary results could be used for conducting and planning large clinical trials and prospective multicentric cohort studies.

    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 10.1101/2020.05.24.20111799 on medRxiv