COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune...

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Main Authors: Silvana Valdebenito, Simon Bessis, Djillali Annane, Geoffroy Lorin de la Grandmaison, Elisabeth Cramer–Bordé, Brendan Prideaux, Eliseo A. Eugenin, Morgane Bomsel
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.735922/full
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author Silvana Valdebenito
Simon Bessis
Djillali Annane
Djillali Annane
Djillali Annane
Geoffroy Lorin de la Grandmaison
Elisabeth Cramer–Bordé
Brendan Prideaux
Eliseo A. Eugenin
Morgane Bomsel
author_facet Silvana Valdebenito
Simon Bessis
Djillali Annane
Djillali Annane
Djillali Annane
Geoffroy Lorin de la Grandmaison
Elisabeth Cramer–Bordé
Brendan Prideaux
Eliseo A. Eugenin
Morgane Bomsel
author_sort Silvana Valdebenito
collection DOAJ
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.
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spelling doaj.art-f80777f5de0a4dfb9d0662a0fc7a9d4c2022-12-21T21:26:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.735922735922COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy CasesSilvana Valdebenito0Simon Bessis1Djillali Annane2Djillali Annane3Djillali Annane4Geoffroy Lorin de la Grandmaison5Elisabeth Cramer–Bordé6Brendan Prideaux7Eliseo A. Eugenin8Morgane Bomsel9Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch (UTMB), Galveston, TX, United StatesService des Maladies Infectieuses, Centre Hospitalier Universitaire Raymond Poincaré, AP-HP, Garches, FranceIntensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, FranceSimone Veil School of Medicine, Université of Versailles, Versailles, FranceUniversity Paris Saclay, Garches, FranceDepartment of Forensic Medicine and Pathology, Versailles Saint-Quentin Université, AP-HP, Raymond Poincaré Hospital, Garches, FranceUniversity of Versailles Saint Quentin en Yveline, Versailles, FranceDepartment of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch (UTMB), Galveston, TX, United StatesDepartment of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch (UTMB), Galveston, TX, United StatesLaboratory of Mucosal Entry of HIV-1 and Mucosal Immunity, Department of Infection, Immunity, and Inflammation, Institute Cochin, CNRS UMR 8104, INSERM U1016, University of Paris, Paris, FranceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.https://www.frontiersin.org/articles/10.3389/fimmu.2021.735922/fullCOVID-19SARS – CoV – 2immuneimmune activationlung
spellingShingle Silvana Valdebenito
Simon Bessis
Djillali Annane
Djillali Annane
Djillali Annane
Geoffroy Lorin de la Grandmaison
Elisabeth Cramer–Bordé
Brendan Prideaux
Eliseo A. Eugenin
Morgane Bomsel
COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
Frontiers in Immunology
COVID-19
SARS – CoV – 2
immune
immune activation
lung
title COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
title_full COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
title_fullStr COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
title_full_unstemmed COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
title_short COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases
title_sort covid 19 lung pathogenesis in sars cov 2 autopsy cases
topic COVID-19
SARS – CoV – 2
immune
immune activation
lung
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.735922/full
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