Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

  1. J. Loske
  2. J. Röhmel
  3. S. Lukassen
  4. S. Stricker
  5. V. G. Magalhães
  6. J. Liebig
  7. R. L. Chua
  8. L. Thürmann
  9. M. Messingschlager
  10. A. Seegebarth
  11. B. Timmermann
  12. S. Klages
  13. M. Ralser
  14. B. Sawitzki
  15. L. E. Sander
  16. V. M. Corman
  17. C. Conrad
  18. S. Laudi
  19. M. Binder
  20. S. Trump
  21. R. Eils
  22. M. A. Mall
  23. I. Lehmann

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  1. Version published to 10.1038/s41587-021-01037-9
  2. ScreenIT

    SciScore for 10.1101/2021.06.24.21259087: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Written informed consent was given by all patients and/or their parents prior to inclusion.
    IRB: All three studies were conducted in accordance with the Declaration of Helsinki and approved by the respective Institutional Review Boards (Pa-COVID-19/ RECAST: EA2/066/20, SC2: 123/20-ek).
    Sex as a biological variableIn total, we analyzed nasal swabs of 45 confirmed SARS-CoV-2 positive patients comprising 24 children with ages ranging from 4 weeks to 17 years (median age 9.0 ± 5.6 years, 10 females, 14 males) and from 21 adults between 21 and 76 years (median age 39.0 ± 10.4 years, 12 females, 9 males).
    RandomizationTo enable visual comparisons between UMAPs of different groups, equal numbers of cell (45,000) per group were randomly sampled using SubsetData function in Seurat.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 infection of MDA5-expressing A549 cells: A549 cells stably transduced with a lentiviral vector expressing human IFIH1 under the control of the murine ROSA26 promoter (termed A549 MDA5high in Fig.
    A549
    suggested: None
    Software and Algorithms
    SentencesResources
    Real-Time Reverse Transcription PCR for SARS-CoV-2: RNA was extracted by using the MagNA pure 96 DNA and viral NA small volume Kit (Roche, https://www.roche.com) on a MagNA Pure 96 System as recommended by the manufacturer.
    https://www.roche.com
    suggested: (Roche, RRID:SCR_001326)
    Putative cell-cell interactions were quantified using CellPhoneDB version 2.1.2 using default settings 39.
    CellPhoneDB
    suggested: (CellPhoneDB, RRID:SCR_017054)
    To test whether elevated MDA5 levels in A549 cells significantly increased IFNB and ISG induction upon infection, an unpaired one-tailed Student-t-test of three biologically independent repetitions was performed (GraphPad Prism v9.1).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.

    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 10.1101/2021.06.24.21259087v1 on medRxiv