Frontiers in Immunology (Apr 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.844727
Journal volume & issue
Vol. 13

Abstract

Read online

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