Low avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19.

Title of publication: 

Low avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19.

Authors: 

Petra Bacher, Elisa Rosati, Daniela Esser, Gabriela Rios Martini, Carina Saggau, Esther Schiminsky, Justina Dargvainiene, Ina Schöder, Imke Wieters, Yascha Khodamoradi, Fabian Eberhardt, Maria J.G.T. Vehreschild, Holger Neb, Michael Sonntagbauer, Claudio Conrad, Florian Tran, Philip Rosenstiel, Robert Markewitz, Klaus-Peter Wandinger, Max Augustin, Jan Rybniker, Matthias Kochanek, Frank Leypoldt, Oliver A. Cornely, Philipp Koehler, Andre Franke, Alexander Scheffold.

Year of Publication: 

2020

medium resp. publishing house / place: 

Immunity

edition / issue: 

Nov.

 CD4+ T cells reactive against SARS-CoV-2 can be found in unexposed individuals and these 43 are suggested to arise in response to common cold corona viruses (CCCoVs) infection. 44 Here, we utilized SARS-CoV-2-reactive CD4+ T cell enrichment to examine the antigen-45 avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-46 reactivity. SARS-CoV-2-reactive CD4+ memory T-cells were present in virtually all 47 unexposed individuals examined, displaying low functional avidity and multiple, highly 48 variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2 reactive CD4+ T 49 cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong 50 memory T-cell responses against CCCoV in all donors analysed. In severe but not mild 51 COVID-19, SARS-CoV-2-specific T-cells displayed low functional avidity and clonality, 52 despite increased frequencies. Our findings identify low avidity CD4+T cell responses as a 53 hallmark of severe COVID-19, and argue against a protective role for CCCoV reactive T cells 54 in SARS-CoV-2 infection.