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

Robinot, R.; Hubert, M.; Dias de Melo, G.; Lazarini, F.; Bruel, T.; Smith, N.; Levallois, S.; Larrous, F.; Fernandes, J.; Gellenoncourt, S.; Rigaud, S.; Gorgette, O.; Thouvenot, C.; Trebeau, C.; Dumenil, G.; Mallet, A.; Gobaa, S.; Etournay, R.; Lledo, P.-M.; Lecuit, M.; Bourhy, H.; Duffy, D.; Michel, V.; Schwartz, O.; Chakrabarti, L. A.

doi:10.1101/2020.10.06.328369

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bioRxiv · 10.1101/2020.10.06.328369

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

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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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Robinot, R., Hubert, M., Dias de Melo, G., Lazarini, F., Bruel, T., Smith, N., Levallois, S., Larrous, F., Fernandes, J., Gellenoncourt, S., Rigaud, S., Gorgette, O., Thouvenot, C., Trebeau, C., Dumenil, G., Mallet, A., Gobaa, S., Etournay, R., Lledo, P.-M., Lecuit, M., Bourhy, H., Duffy, D., Michel, V., Schwartz, O., Chakrabarti, L. A.. 2020-10-06. SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. https://doi.org/10.1101/2020.10.06.328369

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