AUTHOR=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 TITLE=Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.844727 DOI=10.3389/fimmu.2022.844727 ISSN=1664-3224 ABSTRACT=

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.