Current evidence for COVID-19 therapies: a systematic literature review

  1. Tobias Welte
  2. Lucy J. Ambrose
  3. Gillian C. Sibbring
  4. Shehla Sheikh
  5. Hana Müllerová
  6. Ian Sabir

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Abstract

Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively.

In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation versus standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.

This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.

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  1. Version published to 10.1183/16000617.0384-2020
  2. ScreenIT

    SciScore for 10.1101/2020.12.18.20248452: (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

    Software and Algorithms
    SentencesResources
    Search strategy: The systematic literature search was conducted from 1 December 2019 to 14 July 2020 and updated on 14 October 2020, using the electronic databases Embase, MEDLINE® via the PubMed platform and The Cochrane Library.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    Each study was assessed in terms of methodological quality based on criteria consistent with those in the Cochrane Handbook for Systematic Reviews of Interventions and the Cochrane risk-of-bias tool [26, 29].
    Cochrane Handbook
    suggested: None
    Cochrane risk-of-bias tool
    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:
    Limitations include the exclusion of non-English articles from searches, which may have resulted in some relevant trials not being identified. Additionally, the searches were conducted in three major databases but did not include smaller or country-specific databases. Congress abstracts were excluded, on the basis of their data being preliminary and not peer reviewed. Owing to time constraints and the fast-moving nature of the field, a review of citations in the reference lists of published SLRs and meta-analysis was not conducted; and, similarly, the review will not have captured relevant studies published after the date of the final search update. Our ability to analyse and compare the data collected was limited by the significant variation between the trials identified, owing to differences in study design, blinding of participants, severity of illness of participants, drug doses and timing, comparators, follow-up times and outcome definitions. Most trials administered interventions in addition to standard care, which varies between countries and has changed during the pandemic as the body of evidence for the efficacy and safety of different therapies has accumulated. Similarly, the overall lack of high-quality evidence for all interventions makes it difficult to make comparisons between interventions. Most of the trials included in this SLR were assessed as having a high risk of bias in one or more of the domains evaluated, meaning that the results of the analysis of all ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04381936RecruitingRandomised Evaluation of COVID-19 Therapy

    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 10.1101/2020.12.18.20248452v1 on medRxiv