Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia
Sara De Biasi, Marianna Meschiari, Lara Gibellini, Caterina Bellinazzi, Rebecca Borella, Lucia Fidanza, Licia Gozzi, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Annamaria Paolini, Marianna Menozzi, Jovana Milić, Giacomo Franceschi, Riccardo Fantini, Roberto Tonelli, Marco Sita, Mario Sarti, Tommaso Trenti, Lucio Brugioni, Luca Cicchetti, Fabio Facchinetti, Antonello Pietrangelo, Enrico Clini, Massimo Girardis, Giovanni Guaraldi, Cristina Mussini, Andrea Cossarizza
Abstract
Abstract The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1 + CD57 + exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4 + T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.