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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Sci+Immunol 2021 ; 6 (62): ä Nephropedia Template TP
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Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients #MMPMID34376481
Notarbartolo S; Ranzani V; Bandera A; Gruarin P; Bevilacqua V; Putignano AR; Gobbini A; Galeota E; Manara C; Bombaci M; Pesce E; Zagato E; Favalli A; Sarnicola ML; 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
Sci Immunol 2021[Aug]; 6 (62): ä PMID34376481show ga
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.