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Invited speaker:Andrea Cossarizza (ISAC president, University of Modena)
Immune changes during COVID-19 pneumonia
University of Modena and Reggio Emilia School of Medicine, Italy
During the last months, the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a great challenge to the human health, worldwide, with million of infections. We were immediately involved in studying the role of immune system in fighting SARS-CoV2, and have focused our attention on T lymphocytes, B cells and monocytes to investigate the mechanisms underlying the progressive leukopenia observed in patients.
Multiparameter flow cytometry, coupled with unsupervised data analysis, allowed us to find that the T cell compartment in COVID-19 patients with severe pneumonia has several alterations that involve naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells. Several lineage-specifying transcription factors and chemokine receptors are also altered. 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. Dramatic simultaneous increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins were observed in plasma. We then interrogated B cells in these patients, who displayed normal plasma level of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. A decreased number of total and naïve B cells was found, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM- plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle.
Finally, the analysis of monocytes revealed a consistent redistribution of their subsets, with a significant expansion of intermediate/pro-inflammatory cells, a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints, including PD-1/PD-L1. Altered bioenergetics and mitochondrial dysfunction was found, that included a reduced basal and maximal respiration, reduced spare respiratory capacity and decreased proton leak.