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=Volume 13 - 2022

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=Immunopathological pulmonary mechanisms leading to COVID-19-related death in adults remain poorly understood. Broncho-alveolar lavage (BAL) and peripheral blood sampling were performed in 72 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-g and IL-6 levels were decreased in steroid-treated patients when compared to non-steroid treated patients. In lung samples from 3 (1 non-ICU and 2 ICU) additional deceased cases, a lymphocytic memory CD4 T cell angiopathy was observed, co-localizing with SARS-CoV-2 was observed. Taken together, these data show that disease severity occurs despite strong anti-viral CD4T cell specific responses migrating to the lung, whichcould suggest a pathogenic role for perivascular memory CD4 T cells upon fatal COVID-19 pneumonia.