The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

  1. Camila Rosat Consiglio
  2. Nicola Cotugno
  3. Fabian Sardh
  4. Christian Pou
  5. Donato Amodio
  6. Lucie Rodriguez
  7. Ziyang Tan
  8. Sonia Zicari
  9. Alessandra Ruggiero
  10. Giuseppe Rubens Pascucci
  11. Veronica Santilli
  12. Tessa Campbell
  13. Yenan Bryceson
  14. Daniel Eriksson
  15. Jun Wang
  16. Alessandra Marchesi
  17. Tadepally Lakshmikanth
  18. Andrea Campana
  19. Alberto Villani
  20. Paolo Rossi
  21. Nils Landegren
  22. Paolo Palma
  23. Petter Brodin

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Abstract

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  1. ScreenIT

    SciScore for 10.1101/2020.07.08.20148353: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code and data.

    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.

  2. Version published to 10.1016/j.cell.2020.09.016
  3. Version published to 10.1101/2020.07.08.20148353v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2020.07.08.20148353: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe OPBG Ethics Committees approved both studies and informed consent was obtained from parents or guardians of all patients.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Here we have performed a systems-level analysis of immune cells, cytokines and antibodies in the blood of healthy children, children with Kawasaki disease enrolled prior to the COVID-19 pandemic, children infected with SARS-CoV2, and children with MIS-C (Figure 1).
    SARS-CoV2
    suggested: (Abcam Cat# ab273074, AB_2847846)
    An external trigger, likely in the form of a virus is indicated by epidemics of Kawasaki disease, and direct evidence of antiviral antibody responses, particularly targeting viral particles in inclusion bodies in the respiratory epithelium have been reported (Rowley et al., 2008).
    antiviral
    suggested: (Antibodies-Online Cat# ABIN753133, AB_11206991)
    Finally, we perform global autoantibody screening and find strong enrichment in MIS-C of autoantibodies to proteins involved in immune response regulation and structural proteins in the heart, in particular the glycoprotein Endoglin.
    glycoprotein Endoglin.
    suggested: None
    IVIG can neutralize some of the immunopathological effects of autoantibodies found, while corticosteroids provide general immunosuppression and IL-1RA neutralizes the strong IL-1 response likely elicited by endothelial cells and innate immune cells recruited to the site of injury.
    IL-1RA
    suggested: None
    Protein arrays were first incubated with blocking buffer (PA055, Life Technologies) for 1 hour, followed by 90 min incubation with serum at 1:2000 dilution, and 90 min incubation with detection antibodies: Alexa Fluor 647 goat anti-human IgG antibody (A21445, ThermoFisher) at 1:2000 dilution and Dylight 550 goat anti-GST (#DY550011-13-001, Cayman Chemicals) at 1:10,000 dilution.
    anti-human IgG
    suggested: (Thermo Fisher Scientific Cat# A-21445, AB_2535862)
          <div style="margin-bottom:8px">
        <div><b>anti-GST</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">STAR METHODS CONTACT FOR REAGENT AND RESOURCE SHARING Further information and requests for resources and reagents should be directed to Petter Brodin (petter.brodin@ki.se).</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>STAR</b></div>
        <div>suggested: (STAR, <a href="https://scicrunch.org/resources/Any/search?q=SCR_015899">SCR_015899</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">In summary this states that children and adolescents between 0 and 19 years old, with fever > 3 days, and displaying 2 signs among: i) rash or bilateral non purulent conjunctivitis or mucocutaneous inflammation signs, ii) hypotension or shock, iii) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP), iv) evidence of coagulopathy (by PT, PTT, elevated d-Dimers), v) acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain); AND elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin; AND no other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes; AND evidence of SARS-CoV2 infection (RT-PCR or serology positive), or likely exposure to COVID-19 patient.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>ECHO</b></div>
        <div>suggested: (ECHO, <a href="https://scicrunch.org/resources/Any/search?q=SCR_011851">SCR_011851</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Autoantibody profiling Serum autoantibody reactivity was studied using full-length human protein arrays (ProtoArray v5.1, PAH05251020, ThermoFisher)(Zhu et al., 2001).</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>ProtoArray</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Data acquired by CytoFLEX cytometer (Beckman Coulter, Milan, Italy) were analyzed by FlowJo software v.10 (Treestar Software, Ashland, Oregon, USA).</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>FlowJo</b></div>
        <div>suggested: (FlowJo, <a href="https://scicrunch.org/resources/Any/search?q=SCR_008520">SCR_008520</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Graphpad Prism 8 software was used for statistical analysis of demographic and routine laboratory blood tests.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Graphpad Prism</b></div>
        <div>suggested: (GraphPad Prism, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002798">SCR_002798</a>)</div>
      </div>
    </td></tr></table>

    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 OddPub: Thank you for sharing your code and data.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2020.07.08.20148353v1 on medRxiv