CK8⁺ alveolar intermediate differentiation cells are features of alveolar regeneration in SARS-CoV-2 infected hamsters

Einleitung 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.

Material und Methoden This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters.

Befunde 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. At 14 dpi, persistence of ADI cells, M2-type macrophages, and subpleural fibrosis is observed, indicating incomplete alveolar restoration.

Schlussfolgerungen The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients.

Publication History

Article published online:
11 August 2023