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Bacher, Petra; Rosati, Elisa; Esser, Daniela; Martini, Gabriela Rios; Saggau, Carina; Schiminsky, Esther; Dargvainiene, Justina; Schröder, Ina; Wieters, Imke; Khodamoradi, Yascha; Eberhardt, Fabian; Vehreschild, Maria J.G.T.; Neb, Holger; Sonntagbauer, Michael; Conrad, Claudio; Tran, Florian; Rosenstiel, Philip; Markewitz, Robert; Wandinger, Klaus-Peter; Augustin, Max; Rybniker, Jan; Kochanek, Matthias; Leypoldt, Frank; Cornely, Oliver A.; Koehler, Philipp; Franke, Andre; Scheffold, Alexander
Immunity (Cambridge, Mass.), 12/2020, Volume: 53, Issue: 6Journal Article
CD4+ T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4+ T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4+ memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4+ T cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4+ T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection. Display omitted •Low avidity and broad cross-reactivities of pre-existing SARS-CoV-2 memory T cells•Strong CCCoV-specific memory CD4+ T cell responses in all analyzed individuals•SARS-CoV-2-specific CD4+ T cells in COVID-19 patients lack cross-reactivity to CCCoVs•Low avidity and clonality of SARS-CoV-2-specific T cell responses in severe COVID-19 Bacher et al. identify excessive but low-avidity T cell responses to SARS-CoV-2 as a hallmark of severe but not mild COVID-19. Pre-existing memory to SARS-CoV-2 in unexposed donors also displayed low avidity and harbored multiple, highly variable cross-reactivities that were not restricted to common cold coronaviruses.
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