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Hamsters are a model for COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2 (preprint)
biorxiv; 2022.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2022.11.17.515635
ABSTRACT
A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells accumulate following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of p53 at 6- and 14-days post infection (dpi), indicating a prolonged block in the ADI state. Transcriptome data shows the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, persistence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is 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 study provides a suitable translational model for future research on the pathomechanims of PASC and testing of prophylactic and therapeutical approaches.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Fibrosis
/
Coronavirus Infections
/
Adenocarcinoma, Bronchiolo-Alveolar
/
Severe Acute Respiratory Syndrome
/
COVID-19
Language:
English
Year:
2022
Document Type:
Preprint
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