Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection

• Published in: Frontiers in immunology Vol. 13; p. 844727
• Main Authors: Guihot, Amélie, Plu, Isabelle, Soulié, Cathia, Rousseau, Alice, Nakid-Cordero, Cecilia, Dorgham, Karim, Parizot, Christophe, Litvinova, Elena, Mayaux, Julien, Malet, Isabelle, Quentric, Paul, Combadière, Béhazine, Combadière, Christophe, Bonduelle, Olivia, Adam, Lucille, Rosenbaum, Pierre, Beurton, Alexandra, Hémon, Patrice, Debré, Patrice, Vieillard, Vincent, Autran, Brigitte, Seilhean, Danielle, Charlotte, Frédéric, Marcelin, Anne-Geneviève, Gorochov, Guy, Luyt, Charles-Edouard
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 22.04.2022; Frontiers Media S.A
• Subjects: Adaptive immunology; Autopsia; Broncho-alveolar lavage (BAL); COVID-19; Emerging diseases; Human health and pathology; Immunology; Infectious diseases; Life Sciences; Pulmonology and respiratory tract; T cell responses; Vasculitis; COVID-19; Autopsia; Broncho-alveolar lavage (BAL); Vasculitis; T cell responses
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.844727

The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults remain poorly understood. Bronchoalveolar lavage (BAL) and peripheral blood sampling were performed in 74 steroid and non-steroid-treated intensive care unit (ICU) patients (23-75 years; 44 survivors). Peripheral effector SARS-CoV-2-specific T cells were detected in 34/58 cases, mainly directed against the S1 portion of the spike protein. The BAL lymphocytosis consisted of T cells, while the mean CD4/CD8 ratio was 1.80 in non-steroid- treated patients and 1.14 in steroid-treated patients. Moreover, strong BAL SARS-CoV-2 specific T-cell responses were detected in 4/4 surviving and 3/3 non-surviving patients. Serum IFN-γ and IL-6 levels were decreased in steroid-treated patients when compared to non-steroid treated patients. In the lung samples from 3 (1 non-ICU and 2 ICU) additional deceased cases, a lymphocytic memory CD4 T-cell angiopathy colocalizing with SARS-CoV-2 was also observed. Taken together, these data show that disease severity occurs despite strong antiviral CD4 T cell-specific responses migrating to the lung, which could suggest a pathogenic role for perivascular memory CD4 T cells upon fatal COVID-19 pneumonia.