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

Mod Pathol. 2021 Aug;34(8):1444-1455. doi: 10.1038/s41379-021-00808-8. Epub 2021 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biopsy
  • COVID-19 / metabolism
  • COVID-19 / mortality
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Cell Communication*
  • Cytokines / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Endothelial Cells / virology
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Epithelial Cells / virology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Lung / metabolism
  • Lung / pathology*
  • Lung / virology
  • Phosphorylation
  • Prognosis
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • STAT3 Transcription Factor
  • STAT3 protein, human