Rationale and prognosis of repurposed drugs with risk stratification of COVID-19 patients requiring Oxygen supplementation: A systematic review and meta-analysis

  1. Esther Jebarani Elangovan
  2. Vanitha Shyamili Kumar
  3. Adhithyan Kathiravan
  4. Raghav Mallampalli
  5. Tiju Thomas
  6. Gnanasambandam Subramaniyam

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Abstract

Background

The rising number of trials on repurposed dugs in COVID-19 has led to duplication and a need for curation of available outcomes from treatments that have been followed across the world. We have conducted a systematic review and meta-analysis that focus on evaluating the clinical outcomes of repurposed interventions against COVID-19.

Methods

Random effects model was adopted to estimate overall treatment effect and heterogeneity. Meta- regression was performed to study the correlation between comorbid conditions and non- invasive or invasive ventilation requirement.

Results

Twenty-nine articles met our eligibility criteria. In subgroup analysis, Tocilizumab was highly significant with lower mortality rate (OR 27.50; 95%CI [5.39-140.24]) of severe COVID-19 patients. Hydroxychloroquine and Lopinavir-ritonavir was found to be inefficacious in severe patients (OR 0.64; 95%CI [0.47-0.86] and 1.40 [0.71-2.76]). Dexamethasone had marginal effect on overall mortality rate (OR 1.19; 95%CI [1.05-1.35]). The meta-regression shows a positive correlation between prevalence of patients on Tocilizumab in non invasive support and hypertension condition (P = 0.02), whereas a negative correlation was identified with patients having lung disease (P = 0.03).

Conclusion

Overall, our study confirmed that tocilizumab may probably reduce the mortality rate (<10%) of severe COVID-19 patients than other interventions. Further, reduce the risk of requiring non- invasive ventilator support in patients with comorbid condition of lung disease. Hydroxychloroquine and Lopinavir-ritonavir has no clinical benefits in severe COVID-19. A high quality evidence is required to evaluate the usage of Serpin + Favipiravir combination in severe or critical COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.04.20206516: (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 Study Selection: We systematically searched databases including PubMed, medRxiv and Scopus for research articles published from anytime up to 1st August, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    All the data were individually extracted for subgroups (treatment group, control or comparator) and overall outcomes of all the treatments were summarized together and plotted using ggplot2 [18] in R. 2.3 Risk of bias assessment: We used RoB 2.0 [19] and ROBINS-I [20] tools of Cochrane risk of bias assessment for evaluating RCTs and observational or nRCTs.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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:
    Limitation in both studies was that they were soon terminated before attaining enough sample size which prevented definite conclusions of clinical benefits. In our post-search, a large RCT done on CP management was found. This enrolled almost 464 moderately ill COVID-19 patients, and showed results in line with 2 previous RCTs, that mortality was not significantly different between CP treated and control groups 14.5% Vs. 13.5% [47]. According to these reports, CP therapy has shown to be more efficient in early negative conversion of viral RNA, but no effect in reducing the mortality rate of moderate-severe COVID-19 patients. RM shows less or no significance in our subgroup analyses (OR 1.81 [1.15-2.83]; 0.91 [0.41- 2.03]. This shows that it is not effective in reducing the mortality rate for severe COVID-19 patients. Two RCTs with placebo-controlled have been reported, one [30] of which has a larger study size with improvised protocol than the other [31]. The first study [30] favors RM (a 10-day course) over placebo with short recovery time (11 Vs. 15 days) for all clinical outcomes except patients on IMV or ECMO. They further suggest that it is supportive for hospitalized and low supplemental oxygen support patients. A second study [31] trialed 2:1 randomization with limited sample shows no significant reduction of viral load or duration of clinical improvement in severe COVID-19 patients. Both RCTs describe that the mortality rates were insignificant between treatment and p...

    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.

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  2. Version published to 10.1101/2020.10.04.20206516v2 on medRxiv
  3. Version published to 10.1101/2020.10.04.20206516v1 on medRxiv