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Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients

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-Co...

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Autores principales: Croci, Giorgio A., Vaira, Valentina, Trabattoni, Daria, Biasin, Mara, Valenti, Luca, Baselli, Guido, Barberis, Massimo, Guerini Rocco, Elena, Gregato, Giuliana, Scandroglio, Mara, Fominskiy, Evgeny, Palleschi, Alessandro, Rosso, Lorenzo, Nosotti, Mario, Clerici, Mario, Ferrero, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999589/
https://www.ncbi.nlm.nih.gov/pubmed/33801959
http://dx.doi.org/10.3390/cells10030611
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author Croci, Giorgio A.
Vaira, Valentina
Trabattoni, Daria
Biasin, Mara
Valenti, Luca
Baselli, Guido
Barberis, Massimo
Guerini Rocco, Elena
Gregato, Giuliana
Scandroglio, Mara
Fominskiy, Evgeny
Palleschi, Alessandro
Rosso, Lorenzo
Nosotti, Mario
Clerici, Mario
Ferrero, Stefano
author_facet Croci, Giorgio A.
Vaira, Valentina
Trabattoni, Daria
Biasin, Mara
Valenti, Luca
Baselli, Guido
Barberis, Massimo
Guerini Rocco, Elena
Gregato, Giuliana
Scandroglio, Mara
Fominskiy, Evgeny
Palleschi, Alessandro
Rosso, Lorenzo
Nosotti, Mario
Clerici, Mario
Ferrero, Stefano
author_sort Croci, Giorgio A.
collection PubMed
description 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-α. 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.
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spelling pubmed-79995892021-03-28 Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients Croci, Giorgio A. Vaira, Valentina Trabattoni, Daria Biasin, Mara Valenti, Luca Baselli, Guido Barberis, Massimo Guerini Rocco, Elena Gregato, Giuliana Scandroglio, Mara Fominskiy, Evgeny Palleschi, Alessandro Rosso, Lorenzo Nosotti, Mario Clerici, Mario Ferrero, Stefano Cells Article 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-α. 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. MDPI 2021-03-10 /pmc/articles/PMC7999589/ /pubmed/33801959 http://dx.doi.org/10.3390/cells10030611 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Croci, Giorgio A.
Vaira, Valentina
Trabattoni, Daria
Biasin, Mara
Valenti, Luca
Baselli, Guido
Barberis, Massimo
Guerini Rocco, Elena
Gregato, Giuliana
Scandroglio, Mara
Fominskiy, Evgeny
Palleschi, Alessandro
Rosso, Lorenzo
Nosotti, Mario
Clerici, Mario
Ferrero, Stefano
Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title_full Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title_fullStr Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title_full_unstemmed Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title_short Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients
title_sort emergency lung transplantation after covid-19: immunopathological insights on two affected patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999589/
https://www.ncbi.nlm.nih.gov/pubmed/33801959
http://dx.doi.org/10.3390/cells10030611
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