Mortality rates in matched cohort, pseudo-randomised and randomised trials of convalescent plasma given to COVID-19 patients

  1. Amar Ahmad
  2. Marwa Salsabil
  3. Tim Oliver

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Abstract

Introduction

For more than 80 years convalescent or immune sera has been used in severe life threatening infections. Since March of this year a rapidly increasing number of publications have reported series of Convalescent plasma (CP) investigations in severely ill COVID-19 patients.

Objective

a brief CP scoping review focusing on early mortality

Methods

We searched available data bases. Three randomised trials, two pseudo-randomised observations and twelve matched cohort studies were identified. Random-effects meta-analyses were performed on extracted data

Results

A total of 2,378 CP treated and 5188 “controls” in 17 studies. Individually only two studies were significant for reduction of deaths to 30 days, but all showed a similar percentage reduction. When pooled, meta-analysis was undertaken. It showed that the overall reduction of death was significant for all series RR 0.710 (p=0.00001), all matched cohort series RR = 0.610 (p-value = 0.001) and the two pseudo-randomised series RR 0.747 (p=0.005) but not the three technically inadequate randomised trials, RR 0.825 (p=0.397). In two of these randomised trials, there was faster clearance of Viral DNA at 72 hours after CP than placebo

Conclusion

It is hoped the significance of this less than perfect data will increase interest in completing the delayed randomised trials as the results suggest they could be better than currently licenced drugs. Given increasing published evidence of increased risk of both diagnosis and death from COVID-19 in patients with severe Vitamin-D deficiency, future studies should also study influence of Vitamin-D status of donor and recipient on outcome.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.19.20234757: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationTo compared the results with data on established COVID-19 therapies, three randomised trials with Remdesivir (15-17) and one trial with Dexamethasone (18) were reviewed From the review, a total of 16 papers with identified original data comparing convalescent plasma and randomised (n=3), pseudo-randomised (n=2) or matched cohort controls (n=11) were read as full papers.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Searches of Pubmed, EMBASE, Web of Science and ClinicalTrials.gov have been undertaken using the following terms: Convalescent Plasma and COVID-19 and year published 2020.
    Pubmed
    suggested: (PubMed, RRID:SCR_004846)
    At the last search 22.10.2020, 153 references were identified through Medline 143 through EMBASE, 363 through Web of Science and 96 from ClinicalTrials.gov currently recruiting and 16 completed.
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.
    • Thank you for including a protocol registration statement.

    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 10.1101/2020.11.19.20234757v1 on medRxiv