Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

  1. Anjali Ramaswamy
  2. Nina N. Brodsky
  3. Tomokazu S. Sumida
  4. Michela Comi
  5. Hiromitsu Asashima
  6. Kenneth B. Hoehn
  7. Ningshan Li
  8. Yunqing Liu
  9. Aagam Shah
  10. Neal G. Ravindra
  11. Jason Bishai
  12. Alamzeb Khan
  13. William Lau
  14. Brian Sellers
  15. Neha Bansal
  16. Pamela Guerrerio
  17. Avraham Unterman
  18. Victoria Habet
  19. Andrew J. Rice
  20. Jason Catanzaro
  21. Harsha Chandnani
  22. Merrick Lopez
  23. Naftali Kaminski
  24. Charles S. Dela Cruz
  25. John S. Tsang
  26. Zuoheng Wang
  27. Xiting Yan
  28. Steven H. Kleinstein
  29. David van Dijk
  30. Richard W. Pierce
  31. David A. Hafler
  32. Carrie L. Lucas

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Abstract

No abstract available

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  1. Version published to 10.1016/j.immuni.2021.04.003
  2. Version published to 10.1101/2020.12.01.20241364v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.12.01.20241364: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    The cells were then incubated with goat anti-human IgG (H+L) cross-adsorbed secondary antibody, alexa fluor 594 (ThermoFisher, Catalog # A-11014) at 1:400 dilution with FACS buffer.
    anti-human IgG
    suggested: (Innovative Research Cat# A11014, RRID:AB_1500628)
    Experimental Models: Cell Lines
    SentencesResources
    CHI3L1, IFIT2, and IFITM121.
    CHI3L1
    suggested: Coriell Cat# ND26818, RRID:CVCL_GP39)
    Software and Algorithms
    SentencesResources
    The sequencing data was processed using CellRanger v3.1.0.
    CellRanger
    suggested: None
    PBMC single-cell RNA sequencing analysis: Pediatric healthy donor, MIS-C, longitudinal recovered MIS-C, adult healthy donor, and adult COVID-19 PBMC CellRanger outputs were analyzed using the Seurat v3.2.1 package35.
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    Cluster specific markers were found that had an absolute logFC of at least 0.25, an adjusted p-value of less than 0.05, and were expressed in a minimum of 25% of cells in either cluster being compared.
    Cluster
    suggested: (Cluster, RRID:SCR_013505)
    All scRNA-seq plots were done using ggplot2 v3.3.237.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Connectivity mapping: The Connectome v0.2.2 package was used to generate a network analysis of ligand-receptor interactions predicted to be up- or down-regulated in MIS-C compared to C.HD38.
    Connectome
    suggested: (eConnectome, RRID:SCR_009618)
    Heatmaps were visualized using the ComplexHeatmap v2.5.5 package.
    ComplexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)
    Starting with CellRanger output, V(D)J genes for each sequence were aligned to the IMGT reference database v3.1.3044 using IgBlast v1.13.045.
    IgBlast
    suggested: (IgBLAST, RRID:SCR_002873)

    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

    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.

  4. ScreenIT

    SciScore for 10.1101/2020.12.01.20241364: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    The cells were then incubated with goat anti-human IgG (H+L) cross- adsorbed secondary antibody, alexa fluor 594 (ThermoFisher, Catalog # A-11014) at 1:400 dilution with FACS buffer.
    anti-human IgG
    suggested: (Innovative Research Cat# A11014, RRID:AB_1500628)
    Experimental Models: Organisms/Strains
    SentencesResources
    Sample ID P1.1 TSS P2.1 A.HD1 A.HD2 A.HD3 A.COV1.1 A.COV1.2 A.COV2.1 A.COV2.2 A.COV3.1 A.COV3.2 A.COV4.1 A.COV4.2 A.COV5.2 A.COV6.2 A.HD4 A.HD5 A.HD6 A.HD7 A.HD8 A.HD9 A.HD10 A.HD11 A.HD12 A.HD13 P3.1 P4.1 P5.1 P6.1 P7.1 P3.2 P4.2 C.HD1 C.HD2 C.HD3 C.HD4 C.HD5 C.HD6 Condition MIS-C TSS MIS-C A.HD A.HD A.
    A.COV4.2 A.COV5.2 A.COV6.2 A.HD4 A.HD5 A.HD6 A.HD7 A.HD8 A.HD9 A.HD10 A.HD11 A.HD12
    suggested: None
    P4.2 C.HD1 C.HD2 C.HD3 C.HD4 C.HD5 C.HD6
    suggested: None
    HD Subject ID P1 TSS P2 A.HD1 A.HD2 A.HD3 A.COV1 A.COV1 A.COV2 A.COV2 A.COV3 A.COV3 A.COV4 A.COV4 A.COV5 A.COV6 A.HD4 A.HD5 A.HD6 A.HD7 A.HD8 A.HD9 A.HD10 A.HD11 A.HD12 A.HD13 P3 P4 P5 P6 P7 P3 P4 C.HD1 C.HD2 C.HD3 C.HD4 C.HD5 C.HD6 Time point A A A NA NA NA A B A B A B A B B B NA NA NA NA NA NA NA NA NA NA A A A A A B B NA NA NA NA NA NA # days between hosp.
    TSS P2 A.HD1 A.HD2 A.HD3 A.COV1 A.COV1 A.COV2 A.COV2 A.COV3 A.COV3 A.COV4 A.COV4 A.COV5 A.COV6 A.HD4 A.HD5 A.HD6 A.HD7 A.HD8 A.HD9 A.HD10 A.HD11 A.HD12 A.HD13
    suggested: None
    C.HD1 C.HD2 C.HD3 C.HD4 C.HD5 C.HD6
    suggested: None
    Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Kaminski Hafler Hafler Hafler Hafler Hafler Hafler Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2
    Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2 Lucas2
    suggested: None
    Software and Algorithms
    SentencesResources
    The sequencing data was processed using CellRanger v3.1.0.
    CellRanger
    suggested: None
    PBMC single-cell RNA sequencing analysis Pediatric healthy donor, MIS-C, longitudinal recovered MIS-C, adult healthy donor, and adult COVID-19 PBMC CellRanger outputs were analyzed using the Seurat v3.2.1 package35.
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    Cluster specific markers were found that had an absolute logFC of at least 0.25, an adjusted p-value of less than 0.05, and were expressed in a minimum of 25% of cells in either cluster being compared.
    Cluster
    suggested: (Cluster, RRID:SCR_013505)
    All scRNA-seq plots were done using ggplot2 v3.3.237.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Connectivity mapping The Connectome v0.2.2 package was used to generate a network analysis of ligand- receptor interactions predicted to be up- or down-regulated in MIS-C compared to C.HD38.
    Connectome
    suggested: (eConnectome, RRID:SCR_009618)
    Heatmaps were visualized using the ComplexHeatmap v2.5.5 package.
    ComplexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)
    These V(D)J contigs were re-annotated by aligning them to the IMGT reference database v3.1.3041 using IgBlast v1.13.0 in the Change-O V1.0.046 pipeline.
    IgBlast
    suggested: (IgBLAST, RRID:SCR_002873)

    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.

    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.

  5. Version published to 10.1101/2020.12.01.20241364v1 on medRxiv