COVID-19 patients upregulate toll-like receptor 4-mediated inflammatory signaling that mimics bacterial sepsis

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Abstract

Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a cytokine storm is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls. Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

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  1. SciScore for 10.1101/2020.07.17.207878: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Twenty-eight COVID-19 patients (8 SEVERE versus 20 MILD) admitted to Chungnam National University Hospital, and age/sex-matched 20 healthy controls, giving specific informed consent were included in the study.
    IRB: Ethics statement: This study was approved by the Institutional Research and Ethics Committee at Chungnam National University Hospital
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Differentially expressed immune genes (DEiGs) among HC, SEVERE and MILD patients, were satisfied false discovery rate (FDR) < 0.05 which is analyzed and corrected by wilcox.test and p.adjust functions, respectively, implemented in stat package of R (v. 3.6.2).
    MILD
    suggested: (MILD, RRID:SCR_003335)
    The KEGG pathway enrichment analysis was performed using DAVID (version 6.8, https://david.ncifcrf.gov) with a human reference gene set.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    DAVID
    suggested: (DAVID, RRID:SCR_001881)
    To identify chemokine, interleukin, TNF, interferon and those receptor gene families, we downloaded gene family annotations from HUGO Gene Nomenclature Committee (https://www.genenames.org) (38).
    https://www.genenames.org
    suggested: (HGNC, RRID:SCR_002827)

    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.
    • No protocol registration statement was detected.

    About SciScore

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