Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection

Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unk...

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Bibliographic Details
Published in:	JCI insight Vol. 8; no. 1
Main Authors:	Li, Qian, Vijaykumar, Kadambari, Phillips, Scott E, Hussain, Shah S, Huynh, Nha V, Fernandez-Petty, Courtney M, Lever, Jacelyn E Peabody, Foote, Jeremy B, Ren, Janna, Campos-Gómez, Javier, Daya, Farah Abou, Hubbs, Nathaniel W, Kim, Harrison, Onuoha, Ezinwanne, Boitet, Evan R, Fu, Lianwu, Leung, Hui Min, Yu, Linhui, Detchemendy, Thomas W, Schaefers, Levi T, Tipper, Jennifer L, Edwards, Lloyd J, Leal, Jr, Sixto M, Harrod, Kevin S, Tearney, Guillermo J, Rowe, Steven M
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 10-01-2023 American Society for Clinical investigation
Subjects:	Animals COVID-19 COVID-19 - pathology Cricetinae Disease Models, Animal Disease Progression Lung - diagnostic imaging Lung - pathology Mesocricetus Mucociliary Clearance SARS-CoV-2 Subgenomic RNA COVID-19 Respiration
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Summary:	Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes in the MCT apparatus. Both genomic and subgenomic viral RNA pathological and physiological changes were monitored in parallel. We show that SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 days postinfection (dpi) in hamsters, principally due to 79% diminished airway coverage of motile cilia. Correlating quantitation of physiological, virological, and pathological changes reveals steadily descending infection from the upper airways to lower airways to lung parenchyma within 7 dpi. Our results indicate that functional deficits of the MCT apparatus are a key aspect of COVID-19 pathogenesis, may extend viral retention, and could pose a risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell function may indicate disease progression. Therapies directed toward the MCT apparatus deserve further investigation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.163962