Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

De Biasi, Sara; Meschiari, Marianna; Gibellini, Lara; Bellinazzi, Caterina; Borella, Rebecca; Fidanza, Lucia; Gozzi, Licia; Iannone, Anna; Lo Tartaro, Domenico; Mattioli, Marco; Paolini, Annamaria; Menozzi, Marianna; Milić, Jovana; Franceschi, Giacomo; Fantini, Riccardo; Tonelli, Roberto; Sita, Marco; Sarti, Mario; Trenti, Tommaso; Brugioni, Lucio; Cicchetti, Luca; Facchinetti, Fabio; Pietrangelo, Antonello; Clini, Enrico; Girardis, Massimo; Guaraldi, Giovanni; Mussini, Cristina; Cossarizza, Andrea

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.