Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

  1. Zeinab Abdelrahman
  2. Qian Liu
  3. Shanmei Jiang
  4. Mengyuan Li
  5. Qingrong Sun
  6. Yue Zhang
  7. Xiaosheng Wang

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Abstract

Background: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern.

Objective and Methods: To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020.

Results: We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = −0.40, 95% CI: [−0.85, −0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-β (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = −1.09, 95% CI: [−1.64, −0.53]).

Conclusion: Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.

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  1. Version published to 10.3389/fphar.2021.607408
  2. ScreenIT

    SciScore for 10.1101/2020.08.24.20180638: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.1 Search strategy and selection criteria: We searched for publications between January 21, 2020, and May 15, 2020, in databases of PubMed, EMBASE, CNKI, Wanfang, Cochrane library, http://ClinicalTrails.gov, Scopus, Lancet, N Engl J Med and JAMA platforms, and Web of Science.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)
    We used the EndNote X9.0 software to exclude duplicate or irrelevant articles.
    EndNote
    suggested: (EndNote, RRID:SCR_014001)
    We performed the meta-analysis using R software and Cochrane software REVMAN 5[5].
    Cochrane software
    suggested: None
    REVMAN
    suggested: (RevMan, RRID:SCR_003581)
    We assessed the risk of bias in randomized control trials using the Cochrane risk-of-bias tool for randomized trials (ROB-2)[8].
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)

    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:
    This meta-analysis has several limitations. First, we may not include some relevant studies due to certain restrictions in searching for some databases. Second, the quality of evidence is limited by data primarily derived from retrospective analyses, which included heterogeneous data reporting and study design. Third, the confidence of the results from this meta-analysis is limited by insufficient data of the randomized control trials. In conclusion, glucocorticoids, immunoglobulins, RRT, and tocilizumab may worsen outcomes in COVID-19. The most effective and safest treatment strategy for COVID-19 is the combination of different antivirals, supporting the use of antivirals as the basic treatment of COVID-19 with no association with disease progression and mortality. Our data are potentially valuable for clinical treatment and management of COVID-19 patients.

    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 10.1101/2020.08.24.20180638 on medRxiv