ArticleEBioMedicine2024
Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Prolonged dysregulation and pathological changes in the upper respiratory tract of SARS-CoV-2 infected hamsters.Npj viruses · 2026Article
- MOTS‑c protects against placental injury via Nrf2 activation in hypoxia‑induced intrauterine growth restriction mice.International journal of molecular medicine · 2026Article
- Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus.Microorganisms · 2025Article
- Review
- Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.Viruses · 2025Review
- Recruitment of pulmonary intravascular macrophages in SARS-CoV-2 infected hamsters.Cell and tissue research · 2025Article
- Mechanism by which porcine transmissible gastroenteritis virus disrupts host innate immunity.Frontiers in immunology · 2025Review
- Animal models of post-acute COVID-19 syndrome: a call for longitudinal animal studies.Frontiers in immunology · 2025Review
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17 authors.
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Abstract
backgroundPost-acute sequalae of COVID-19 defines a wide range of ongoing symptoms and conditions long after SARS-CoV-2 infection including respiratory diseases. The histopathological changes in the lung and underlying mechanism remain elusive.
methodsWe investigated lung histopathological and transcriptional changes in SARS-CoV-2-infected male hamsters at 7, 14, 42, 84 and 120dpi, and compared with A (H1N1)pdm09 infection.
findingsWe demonstrated viral residue, inflammatory and fibrotic changes in lung after SARS-CoV-2 but not H1N1 infection. The most prominent histopathological lesion was multifocal alveolar-bronchiolization observed in every SARS-CoV-2 infected hamster (31/31), from 42dpi to 120dpi. Proliferating (Ki67+) CK14+ basal cells accumulated in alveoli adjacent to bronchioles at 7dpi, where they proliferated and differentiated into SCGB1A+ club cell or Tubulin+ ciliated cells forming alveolar-bronchiolization foci. Molecularly, Notch pathway significantly upregulated with intensive Notch3 and Hes1 protein expression in alveolar-bronchiolization foci at 42 and 120dpi, suggesting Notch signaling involving the persistence of alveolar-bronchiolization. This is further demonstrated by spatial transcriptomic analysis. Intriguingly, significant upregulation of some cell-growth promoting pathways and genes such as Tubb4b, Stxbp4, Grb14 and Mlf1 were spatially overlapping with bronchiolization lesion.
interpretationIncomplete resolution of SARS-CoV-2 infection in lung with viral residue, chronic inflammatory and fibrotic damage and alveolar-bronchiolization impaired respiratory function. Aberrant activation of CK14+ basal cells during tissue regeneration led to persistent alveolar-bronchiolization due to sustained Notch signaling. This study advances our understanding of respiratory PASC, sheds light on disease management and highlights the necessity for monitoring disease progression in people with respiratory PASC.
fundingFunding is listed in the Acknowledgements section.
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