To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.

Notarbartolo, S., Ranzani, V., Bandera, A., Gruarin, P., Bevilacqua, V., Putignano, A., et al. (2021). Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients. SCIENCE IMMUNOLOGY, 6(62) [10.1126/sciimmunol.abg5021].

Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients

Gobbini A.;Granucci F.;
2021

Abstract

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.
Articolo in rivista - Articolo scientifico
Scientifica
Adult; Aged; Antibodies, Viral; B-Lymphocytes; Biomarkers; COVID-19; Cell Plasticity; Clonal Evolution; Female; Gene Expression Profiling; Host-Pathogen Interactions; Humans; Immunoglobulin Isotypes; Immunologic Memory; Leukocytes, Mononuclear; Lymphocyte Count; Male; Middle Aged; SARS-CoV-2; T-Lymphocyte Subsets; Immunophenotyping; Transcriptome;
English
Notarbartolo, S., Ranzani, V., Bandera, A., Gruarin, P., Bevilacqua, V., Putignano, A., et al. (2021). Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients. SCIENCE IMMUNOLOGY, 6(62) [10.1126/sciimmunol.abg5021].
Notarbartolo, S; Ranzani, V; Bandera, A; Gruarin, P; Bevilacqua, V; Putignano, A; Gobbini, A; Galeota, E; Manara, C; Bombaci, M; Pesce, E; Zagato, E; Favalli, A; Sarnicola, M; Curti, S; Crosti, M; Martinovic, M; Fabbris, T; Marini, F; Donnici, L; Lorenzo, M; Mancino, M; Ungaro, R; Lombardi, A; Mangioni, D; Muscatello, A; Aliberti, S; Blasi, F; De Feo, T; Prati, D; Manganaro, L; Granucci, F; Lanzavecchia, A; De Francesco, R; Gori, A; Grifantini, R; Abrignani, S
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/349342
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