Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

  1. Emanuel Wyler
  2. Julia M. Adler
  3. Kathrin Eschke
  4. G. Teixeira Alves
  5. Stefan Peidli
  6. Fabian Pott
  7. Julia Kazmierski
  8. Laura Michalick
  9. Olivia Kershaw
  10. Judith Bushe
  11. Sandro Andreotti
  12. Peter Pennitz
  13. Azza Abdelgawad
  14. Dylan Postmus
  15. Christine Goffinet
  16. Jakob Kreye
  17. S Momsen Reincke
  18. Harald Prüss
  19. Nils Blüthgen
  20. Achim D. Gruber
  21. Wolfgang M. Kuebler
  22. Martin Witzenrath
  23. Markus Landthaler
  24. Geraldine Nouailles
  25. Jakob Trimpert

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Abstract

No abstract available

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  1. Version published to 10.1016/j.ymthe.2022.03.014
  2. ScreenIT

    SciScore for 10.1101/2021.12.17.473180: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableEthics statement and COVID-19 hamster models: Experiments including female and male hamsters (Mesocricetus auratus; breed RjHan:AURA, JanvierLabs, France) and Roborovski hamster (Phodopus roborovskii, via German pet trade) were approved and executed in compliance with all applicable regulations (permit number 0086/20).
    Randomizationnot detected.
    BlindingHistopathology and in situ-hybridization of SARS-CoV-2 RNA: For histopathology and in situ-hybridization (ISH), lungs were processed, and tissues evaluated by board-certified veterinary pathologists in a blinded fashion following standardized recommendations, including pneumonia-specific scoring parameters as described previously (24).
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Raw and processed data is available through GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE191080, code through Github at https://github.com/Berlin-Hamster-Single-Cell-Consortium/Dwarf-Hamster-Dexamethasone-Antibody.
    acc=GSE191080
    suggested: None
    Software and Algorithms
    SentencesResources
    Annotations of the M. auratus and P. roborowskii genome: The M. auratus genome was derived from Ensembl and modified as previously described (25).
    Ensembl
    suggested: (Ensembl, RRID:SCR_002344)
    Reads were aligned to the genome using hisat2 (27) and gene expression quantified using quasR (27).
    hisat2
    suggested: (HISAT2, RRID:SCR_015530)
    quasR
    suggested: (QUASR, RRID:SCR_006820)

    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: We detected the following sentences addressing limitations in the study:
    That notwithstanding, future studies should ideally compare patient data to the findings reported here with the obvious constraint of limitations in the availability of corresponding human biomaterial. In summary, we found that broadly active anti-inflammatory and immunosuppressive agents such as dexamethasone may have a strong benefit in SARS-CoV-2 infection at high risk for severe disease when applied before the onset of severe illness, particularly when combined with an anti-viral agent. A recent analysis showed that COVID-19-related ARDS patients can be classified into hypo- and hyperinflammatory types, with corticosteroid treatment being beneficial only for the latter (51). Animal models as the ones described here can help to better dissect causes and types of COVID-19 lung pathologies, and thus help to improve therapeutic strategies.

    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 10.1101/2021.12.17.473180v1 on bioRxiv