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 TCM and 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.

Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients / S. Notarbartolo, V. Ranzani, A. Bandera, P. Gruarin, V. Bevilacqua, A.R. Putignano, A. Gobbini, E. Galeota, C. Manara, M. Bombaci, E. Pesce, E. Zagato, A. Favalli, M.L. Sarnicola, S. Curti, M. Crosti, M. Martinovic, T. Fabbris, F. Marini, L. Donnici, M. Lorenzo, M. Mancino, R. Ungaro, A. Lombardi, D. Mangioni, A. Muscatello, S. Aliberti, F. Blasi, T. De Feo, D. Prati, L. Manganaro, F. Granucci, A. Lanzavecchia, R. De Francesco, A. Gori, R. Grifantini, S. Abrignani. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 6:62(2021 Aug 10), pp. 1-18. [10.1126/sciimmunol.abg5021]

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

Notarbartolo, Samuele;Ranzani, Valeria;Bandera, Alessandra;Bevilacqua, Valeria;Putignano, Anna Rita;Manara, Cristina;Pesce, Elisa;Zagato, Elena;Curti, Serena;Martinovic, Martina;Marini, Federico;Donnici, Lorena;Lorenzo, Mariangela;Mancino, Marilena;Ungaro, Riccardo;Lombardi, Andrea;Mangioni, Davide;Aliberti, Stefano;Blasi, Francesco;De Feo, Tullia;Manganaro, Lara;De Francesco, Raffaele;Gori, Andrea;Abrignani, Sergio
2021-08-10

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 TCM and 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.
Settore MED/04 - Patologia Generale
Settore BIO/19 - Microbiologia Generale
SCIENCE IMMUNOLOGY
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/864089
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