The pathogenic role of epithelial and endothelial cells in early-phase COVID-19 pneumonia: victims and partners in crime
Marco Chilosi, Venerino Poletti, Claudia Ravaglia, Giulio Rossi, Alessandra Dubini, Sara Piciucchi, Federica Pedica, Vincenzo Bronte, Giovanni Pizzolo, Guido Martignoni, Claudio Doglioni
Abstract
Current understanding of the complex pathogenesis of COVID-19 interstitial pneumonia pathogenesis in the light of biopsies carried out in early/moderate phase and histology data obtained at postmortem analysis is discussed. In autopsies the most observed pattern is diffuse alveolar damage with alveolar-epithelial type-II cell hyperplasia, hyaline membranes, and frequent thromboembolic disease. However, these observations cannot explain some clinical, radiological and physiopathological features observed in SARS-CoV-2 interstitial pneumonia, including the occurrence of vascular enlargement on CT and preserved lung compliance in subjects even presenting with or developing respiratory failure. Histological investigation on early-phase pneumonia on perioperative samples and lung biopsies revealed peculiar morphological and morpho-phenotypical changes including hyper-expression of phosphorylated STAT3 and immune checkpoint molecules (PD-L1 and IDO) in alveolar-epithelial and endothelial cells. These features might explain in part these discrepancies.