COVID-19 survivors often experience post-acute sequelae of SARS-CoV-2 infection (PASC). This study uses a Syrian golden hamster model to investigate alveolar regeneration after SARS-CoV-2 infection. The findings show that CK8+ alveolar differentiation intermediate (ADI) cells appear after SARS-CoV-2-induced diffuse alveolar damage, with some showing prolonged arrest. Transcriptomic data reveals pathways involved in senescence, EMT, and angiogenesis. Airway basal cells also contribute to alveolar regeneration. Incomplete alveolar restoration and fibrosis are observed at 14 days post-infection, mimicking aspects of dysregulated regeneration in COVID-19 patients. This hamster model offers a valuable tool for researching PASC and testing therapeutic approaches.

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