Metabolic stress and disease-stage specific basigin expression of peripheral blood immune cell subsets in COVID-19 patients

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Abstract

Coronavirus disease 2019 (COVID-19) is driven by dysregulated immune responses yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 47 patients with confirmed SARS-CoV-2 infection and 16 uninfected controls, we found an immunometabolic dysregulation specific for patients with progressed disease that was reversible in the recovery phase. Specifically, T cells and monocytes exhibited increased mitochondrial mass, accumulated intracellular ROS and these changes were accompanied by disrupted mitochondrial architecture. Basigin (CD147), but not established markers of T cell activation, was up-regulated on T cells from progressed COVID-19 patients and correlated with ROS accumulation, reflected in the transcriptome. During recovery, basigin and ROS decreased to match the uninfected controls. In vitro analyses confirmed the correlation and showed a down-regulation of ROS by dexamethasone treatment. Our findings provide evidence of a basigin-related and reversible immunometabolic dysregulation in COVID-19.

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  1. SciScore for 10.1101/2020.09.18.20194175: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the appropriate Institutional Review Board (University Hospital Regensburg, No. 20-1785-101) and conformed to the principles outlined in the Declaration of Helsinki.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableControls were asymptomatic healthy individuals with age median of 46.7 (IQR 37.25-46.7) and male sex in 47%.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody response was defined by presence of SARS-CoV-2 specific IgG antibodies in serum.
    SARS-CoV-2 specific IgG
    suggested: None
    Cells were stained with surface antibodies as described above and incubated in with 2-NBDG (45 min) or BODIPY 500/510 C1, C12 (20 min).
    C12
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 infection of A549 cells was performed and published by Blanco-Melo et al (Blanco-Melo et al., 2020).
    A549
    suggested: None
    Software and Algorithms
    SentencesResources
    Tables of raw uniquely mapped read counts per human gene were generated during mapping using the built-in --quantMode GeneCounts option in STAR.
    STAR
    suggested: (STAR, RRID:SCR_015899)
    Differential expression analysis was carried out on raw gene counts using edgeR 3.20.8 (Robinson et al., 2009) in R (3.4.3).
    edgeR
    suggested: (edgeR, RRID:SCR_012802)
    Volcano plots were generated using the ggplot2 (v3.1.0) package in R.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    The rank-based gene set enrichment tests in Figure 5 were done using the fry function of the limma package (Ritchie et al., 2015) and plotted using the barcodeplot function in R.
    limma
    suggested: (LIMMA, RRID:SCR_010943)
    Gene-sets were defined in the hallmark gene set collection (Liberzon et al., 2015) and basigin interaction partners were defined by STRING (Szklarczyk et al., 2019).
    STRING
    suggested: (STRING, RRID:SCR_005223)
    Statistics: GraphPad Prism was used for statistical analyses, using ANOVA with post-hoc Bonferroni test and Mann-Whitney U test.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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
    NCT04275245RecruitingClinical Study of Anti-CD147 Humanized Meplazumab for Inject…


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 26. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.