Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

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Abstract

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16 + monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

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  1. SciScore for 10.1101/2021.02.10.430668: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Both studies had received prior approval from their respective institutional review boards (IRBs).
    RandomizationAfter CyTOF acquisition, data were exported in flow-cytometry (FCS) format, normalized to 300,000 PBMCs and events with parameters having zero values were randomized using a uniform distribution of values between minus-one and zero.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAll individuals involved in this study were over the age of 21, comprising 66 males and 21 females.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Enrollment of COVID-19 patients was via PROTECT, a Singapore COVID-19 cohort study among seven public health institutions.
    PROTECT
    suggested: (ProTECT, RRID:SCR_004531)
    Data analysis was done on Bio-Plex Manager™ 6.1.1 (Bio-Rad).
    Bio-Plex
    suggested: None
    Heat maps were generated in R version 3.6.2 using the CompexHeatmap package.
    CompexHeatmap
    suggested: None
    Graphs of the significant associations were generated in R version 3.6.2 using the iGraph package and visualized in Cytoscape version 3.8.0.
    iGraph
    suggested: (igraph, RRID:SCR_019225)
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 49. 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 scite Reference Check: We found no unreliable references.


    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.