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

Amélie Guihot (1, 2) , Isabelle Plu (2) , Cathia Soulié (3, 2) , Alice Rousseau (1) , Cecilia Nakid-Cordero (1) , Karim Dorgham (1) , Christophe Parizot (2) , Elena Litvinova (2) , Julien Mayaux (2) , Isabelle Malet (3, 2) , Paul Quentric (1) , Béhazine Combadière (1) , Christophe Combadière (1) , Olivia Bonduelle (1) , Lucille Adam (1) , Pierre Rosenbaum (1) , Alexandra Beurton (2) , Patrice Hémon (4) , Patrice Debré (1) , Vincent Vieillard (1) , Brigitte Autran (1) , Danielle Seilhean (2) , Frédéric Charlotte (2) , Anne-Geneviève Marcelin (3, 2) , Guy Gorochov (1, 2) , Charles-Edouard Luyt (5, 2)

1 CIMI - Centre d'Immunologie et des Maladies Infectieuses
2 CHU Pitié-Salpêtrière [AP-HP]
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
5 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]

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.

Keywords: Autopsia; Broncho-alveolar lavage (BAL); COVID-19; T cell responses; Vasculitis

Domains: Life Sciences [q-bio]

Amélie Guihot, Isabelle Plu, Cathia Soulié, Alice Rousseau, Cecilia Nakid-Cordero, et al.. Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection. Frontiers in Immunology, 2022, 13, pp.844727. ⟨10.3389/fimmu.2022.844727⟩. ⟨hal-03745734⟩