The pathogenic role of epithelial and endothelial cells in early-phase COVID-19 pneumonia: victims and partners in crime

• Published in: Modern pathology Vol. 34; no. 8; pp. 1444 - 1455
• Main Authors: Chilosi, Marco, Poletti, Venerino, Ravaglia, Claudia, Rossi, Giulio, Dubini, Alessandra, Piciucchi, Sara, Pedica, Federica, Bronte, Vincenzo, Pizzolo, Giovanni, Martignoni, Guido, Doglioni, Claudio
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.08.2021; Nature Publishing Group US; Elsevier Limited
• Subjects: 13/51; 631/250/254; 692/420/254; Alveoli; B7-H1 Antigen - metabolism; Biopsy; Cell Communication; Coronaviruses; COVID-19; COVID-19 - metabolism; COVID-19 - mortality; COVID-19 - pathology; COVID-19 - virology; Cytokines - metabolism; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelial Cells - virology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelial Cells - virology; Humans; Hyperplasia; Immune checkpoint; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Laboratory Medicine; Lung - metabolism; Lung - pathology; Lung - virology; Medicine; Medicine & Public Health; Pathogenesis; Pathology; PD-L1 protein; Phosphorylation; Pneumonia; Prognosis; Respiratory failure; Review; Review Article; Severe acute respiratory syndrome coronavirus 2; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - metabolism; Thromboembolism
• ISSN: 0893-3952; 1530-0285; 1530-0285
• DOI: 10.1038/s41379-021-00808-8

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.