Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity

  1. Nicholas S. Giroux
  2. Shengli Ding
  3. Micah T. McClain
  4. Thomas W. Burke
  5. Elizabeth Petzold
  6. Hong A. Chung
  7. Grecia R. Palomino
  8. Ergang Wang
  9. Rui Xi
  10. Shree Bose
  11. Tomer Rotstein
  12. Bradly P. Nicholson
  13. Tianyi Chen
  14. Ricardo Henao
  15. Gregory D. Sempowski
  16. Thomas N. Denny
  17. Emily R. Ko
  18. Geoffrey S. Ginsburg
  19. Bryan D. Kraft
  20. Ephraim L. Tsalik
  21. Christopher W. Woods
  22. Xiling Shen

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Abstract

SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects.

One sentence summary

Chromatin accessibility in immune cells from COVID-19 subjects is remodeled prior to seroconversion to reflect disease severity.

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  1. Version published to 10.1101/2020.12.04.412155v3 on bioRxiv
  2. Version published to 10.1101/2020.12.04.412155v2 on bioRxiv
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    SciScore for 10.1101/2020.12.04.412155: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from all research participants or their legally authorized representatives (LAR).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 IgG ELISA: Antibody response testing was performed using the anti-SARS-CoV-2 IgG ELISA assay (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany) according to manufacturer’s instructions.
    anti-SARS-CoV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    The sequencing datasets and related clinical metadata tables will be made available via the Gene Expression Omnibus (GEO) repository prior to publication.
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Sequencing data were used as input to the 10x Genomics Cell Ranger ATAC pipeline to demultiplex BCL files, generate FASTQs, and generate feature counts for each library.
    ATAC
    suggested: (Atac, RRID:SCR_015980)

    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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  4. Version published to 10.1101/2020.12.04.412155v1 on bioRxiv