Journal Article

Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2

Kühnel, Mark, Becker, Kathrin, Beythien, Georg, Armando, Federico, Zickler, Martin, Beck, Sebastian, Beineke, Andreas, Baumgärtner, Wolfgang, Schaumburg, Berfin, Mounogou-Kouassi, Nancy, Ciurkiewicz, Małgorzata, Schughart, Klaus, Heydemann, Laura, Stanelle-Bertram, Stephanie, Gabriel, Gülsah

2023

Overview

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).

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/51 / 14/28 / 14/63 / 38/91 / 631/326/596/4130 / 692/420/254 / 692/699/255/2514 / Alveolar Epithelial Cells / Alveoli / Angiogenesis / Animal models / Animals / Cell Differentiation / Cell migration / Complications / COVID-19 / Cricetinae / Damage accumulation / Disease Progression / Fibrosis / Gene expression / Hamsters / Humanities and Social Sciences / Humans / Infections / Macrophages / Mesocricetus / multidisciplinary / p53 Protein / Post-Acute COVID-19 Syndrome / Progenitor cells / Regeneration / SARS-CoV-2 / Science / Science (multidisciplinary) / Senescence / Severe acute respiratory syndrome coronavirus 2 / Transcriptomes / Transcriptomics