%0 Journal Article %T COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases %T Pathogenèse du COVID-19 pulmonaire dans les autopsies de sujets infectés par SARS-CoV-2 %+ University of Texas Medical Branch at Galveston %+ Hôpital Raymond Poincaré [AP-HP] %+ Infection et inflammation (2I) %+ Université Paris-Saclay %+ Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) %+ Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) %+ Institut Cochin (IC UM3 (UMR 8104 / U1016)) %A Valdebenito, Silvana %A Bessis, Simon %A Annane, Djillali %A Lorin de La Grandmaison, Geoffroy %A Cramer Bordé, Elisabeth %A Prideaux, Brendan %A Eugenin, Eliseo, A %A Bomsel, Morgane %< avec comité de lecture %@ 1664-3224 %J Frontiers in Immunology %I Frontiers %V 12 %N 535 %P eaat6263 %8 2021 %D 2021 %R 10.3389/fimmu.2021.735922 %K COVID-19 %K SARS -CoV -2 %K immune %K immune activation %K lung %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseases %Z Life Sciences [q-bio]/Human health and pathology/Emerging diseases %Z Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract %Z Life Sciences [q-bio]/Immunology/Innate immunity %Z Life Sciences [q-bio]/Immunology/Adaptive immunologyJournal articles %X 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. %G English %2 https://cnrs.hal.science/hal-03367726/document %2 https://cnrs.hal.science/hal-03367726/file/COVID%20Autopsy%20%20Frintiers%20Immunol%2021%2C%20%20Eliseo%2CValdebenito%20.pdf %L hal-03367726 %U https://cnrs.hal.science/hal-03367726 %~ INSERM %~ CNRS %~ APHP %~ UVSQ %~ UNIV-PARIS-SACLAY %~ 2IC %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ TEST-HALCNRS %~ UVSQ-UPSACLAY %~ UNIVERSITE-PARIS-SACLAY %~ GS-LIFE-SCIENCES-HEALTH %~ GS-HEALTH-DRUG-SCIENCES