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- Title
Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2.
- Authors
Heydemann, Laura; Ciurkiewicz, Małgorzata; Beythien, Georg; Becker, Kathrin; Schughart, Klaus; Stanelle-Bertram, Stephanie; Schaumburg, Berfin; Mounogou-Kouassi, Nancy; Beck, Sebastian; Zickler, Martin; Kühnel, Mark; Gabriel, Gülsah; Beineke, Andreas; Baumgärtner, Wolfgang; Armando, Federico
- Abstract
COVID-19 survivors often suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Current evidence suggests dysregulated alveolar regeneration as a possible explanation for respiratory PASC, which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show high module scores for pathways involved in cell senescence, epithelial-mesenchymal transition, and angiogenesis in cell clusters with high ADI gene expression. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, ADI cells, peribronchiolar proliferates, M2-macrophages, and sub-pleural fibrosis are observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome. Heydemann et al. investigate alveolar regeneration mechanisms after SARS-CoV-2 infection in the hamster model, offering insight into the pathomechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).
- Subjects
POST-acute COVID-19 syndrome; GOLDEN hamster; HAMSTERS; COVID-19 pandemic; SARS-CoV-2; COVID-19; CELLULAR aging
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39049-5