Hidden in plain sight: The effects of BCG vaccination in the COVID‐19 pandemic

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Abstract

To investigate the relationship between Bacille Calmette‐Guérin (BCG) vaccination and SARS‐CoV‐2 by a bioinformatics approach, two datasets for the SARS‐CoV‐2 infection group and BCG‐vaccinated group were downloaded. Differentially Expressed Genes were identified. Gene ontology and pathways were functionally enriched, and networking was constructed in NetworkAnalyst. Lastly, the correlation between post‐BCG vaccination and COVID‐19 transcriptome signatures was established. A total of 161 DEGs (113 upregulated DEGs and 48 downregulated genes) were identified in the SARS‐CoV‐2 group. In the pathway enrichment analysis, a cross‐reference of upregulated Kyoto Encyclopedia of Genes and Genomes pathways in SARS‐CoV‐2 with downregulated counterparts in the BCG‐vaccinated group, resulted in the intersection of 45 common pathways, accounting for 86.5% of SARS‐CoV‐2 upregulated pathways. Of these intersecting pathways, a vast majority were immune and inflammatory pathways with top significance in interleukin‐17, tumor necrosis factor, NOD‐like receptors, and nuclear factor‐κB signaling pathways. Given the inverse relationship of the specific differentially expressed gene pathways highlighted in our results, the BCG‐vaccine may play a protective role against COVID‐19 by mounting a nonspecific immunological response and further investigation of this relationship is warranted.

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  1. SciScore for 10.1101/2020.06.09.142760: (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
    Gene set enrichment analysis in Tuberculosis pathway (KEGG ID: hsa05152).
    Gene set enrichment analysis
    suggested: (Gene Set Enrichment Analysis, RRID:SCR_003199)
    d upregulated KEGG pathways in SARS-COV-2 infected cells that are reversed following BCG vaccination.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04347876RecruitingOutcome of COVID-19 Cases Based on Tuberculin Test: Can Prev…
    NCT04327206RecruitingBCG Vaccination to Protect Healthcare Workers Against COVID-…
    NCT04328441Active, not recruitingReducing Health Care Workers Absenteeism in Covid-19 Pandemi…
    NCT04348370RecruitingBCG Vaccine for Health Care Workers as Defense Against COVID…
    NCT04350931Not yet recruitingApplication of BCG Vaccine for Immune-prophylaxis Among Egyp…


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.
    • No funding statement was detected.
    • 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.