Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children

  1. Brittany P. Boribong
  2. Thomas J. LaSalle
  3. Yannic C. Bartsch
  4. Felix Ellett
  5. Maggie E. Loiselle
  6. Jameson P. Davis
  7. Anna L.K. Gonye
  8. David B. Sykes
  9. Soroush Hajizadeh
  10. Johannes Kreuzer
  11. Shiv Pillai
  12. Wilhelm Haas
  13. Andrea G. Edlow
  14. Alessio Fasano
  15. Galit Alter
  16. Daniel Irimia
  17. Moshe Sade-Feldman
  18. Lael M. Yonker

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Abstract

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  1. Version published to 10.1016/j.xcrm.2022.100848
  2. ScreenIT

    SciScore for 10.1101/2021.12.18.473308: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study Design: Biospecimens were obtained from pediatric patients at Massachusetts General Hospital (MGH) under the institutional review board (IRB) approved ‘MGH Pediatric COVID-19 Biorepository’ (no.
    Consent: Informed consent, and assent when appropriate, were obtained in accordance with IRB guidelines from patients and/or parents/guardians before study enrollment.
    Field Sample Permit: After plasma collection, PBMCs were isolated and collected via Ficoll density gradient.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Differential expression and GSEA results.
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We acknowledge several limitations of our study. First, we utilized bulk transcriptomics due to the technical challenges of performing single-cell RNA-sequencing on neutrophils, so each sample represents a mixture of neutrophils with distinct gene expression programs. However, our high purity double isolation method left little contamination with other cell types. Second, we acknowledge the small size of the cohort, although it represents the largest cohort of its kind due to the low incidence rate of the disease. Third, based on the sample size limitation we were unable to define new gene expression states that may have been specific to pediatric neutrophils and had to rely on the adult-derived signatures, though that work demonstrated a relatively small set of conserved neutrophil states across many different disease contexts. Fourth, MIS-C can present heterogeneously and there was a mixture of treatment regimens and duration of disease among the patients, which may have resulted in greater heterogeneity in the gene expression profiles. All limitations considered, numerous technical challenges and time-sensitive issues were overcome in this study to allow for deep characterization of neutrophil profiles in acute pediatric COVID-19 and MIS-C. In summary, our study provides much needed mechanistic insight into the drivers of pathology in MIS-C and its departure from mild acute SARS-CoV-2 infection in children. We link existing knowledge of gut mucosal breakdown and antigenemi...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    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.

  3. Version published to 10.1101/2021.12.18.473308v1 on bioRxiv