Journal
CELLS
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cells10030611
Keywords
SARS-CoV-2; COVID-19; ARDS; usual interstitial pneumonia; immunology; lung transplantation
Categories
Funding
- Covid-19 Biobank [RC100017A]
- Ricerca Corrente program 2020 from the Italian Minister of Health
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- [RF-201602364358]
Ask authors/readers for more resources
This study characterized the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation, revealing extensive lung damage resembling usual interstitial pneumonia. Gene expression profiling in lung tissues and stimulated blood cells showed overexpression of immune-related genes and a persistent proinflammatory state, indicating sustained immune activation despite immunosuppression.
We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs' GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-alpha. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available