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

Autor:	Notarbartolo S; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Ranzani V; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Bandera A; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.; Centre for Multidisciplinary Research in Health Science (MACH), Università degli Studi di Milano, Milan, Italy., Gruarin P; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Bevilacqua V; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Putignano AR; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy., Gobbini A; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy., Galeota E; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Manara C; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Bombaci M; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Pesce E; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Zagato E; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy., Favalli A; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Sarnicola ML; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Curti S; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Crosti M; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Martinovic M; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Fabbris T; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Marini F; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Mainz, Germany., Donnici L; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Lorenzo M; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Mancino M; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Ungaro R; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Lombardi A; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Mangioni D; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Muscatello A; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Aliberti S; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.; Respiratory Unit and Cystic Fibrosis Adult Center, Respiratory Unit and Cystic Fibrosis Adult Center., Blasi F; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.; Respiratory Unit and Cystic Fibrosis Adult Center, Respiratory Unit and Cystic Fibrosis Adult Center., De Feo T; Unità Operativa Complessa (UOC) Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy., Prati D; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Transfusion Medicine and Hematology, Milan, Italy., Manganaro L; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Granucci F; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy., Lanzavecchia A; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., De Francesco R; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy., Gori A; Infectious Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.; Centre for Multidisciplinary Research in Health Science (MACH), Università degli Studi di Milano, Milan, Italy., Grifantini R; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy., Abrignani S; INGM, Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2021 Aug 10; Vol. 6 (62).
DOI:	10.1126/sciimmunol.abg5021
Abstrakt:	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 T CM and T H 2-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. (Copyright © 2021, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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