SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance

  1. Rémy Robinot
  2. Mathieu Hubert
  3. Guilherme Dias de Melo
  4. Françoise Lazarini
  5. Timothée Bruel
  6. Nikaïa Smith
  7. Sylvain Levallois
  8. Florence Larrous
  9. Julien Fernandes
  10. Stacy Gellenoncourt
  11. Stéphane Rigaud
  12. Olivier Gorgette
  13. Catherine Thouvenot
  14. Céline Trébeau
  15. Adeline Mallet
  16. Guillaume Duménil
  17. Samy Gobaa
  18. Raphaël Etournay
  19. Pierre-Marie Lledo
  20. Marc Lecuit
  21. Hervé Bourhy
  22. Darragh Duffy
  23. Vincent Michel
  24. Olivier Schwartz
  25. Lisa A. Chakrabarti

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Abstract

Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. We examined the functional and structural consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. SARS-CoV-2 replication caused a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remained limited. Rather, SARS-CoV-2 replication led to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. The motile cilia function was compromised, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramped up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrated the loss of motile cilia in vivo . This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.

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    SciScore for 10.1101/2020.10.06.328369: (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: 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

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  2. Version published to 10.1101/2020.10.06.328369v1 on bioRxiv