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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms determining such variable outcomes remain unresolved. Here, we investigated SARS-CoV-2 spike glycoprotein (S)-reactive CD4+ T cells in peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors (HD). We detected SARS-CoV-2 S-reactive CD4+ T cells in 83% of patients with COVID-19 but also in 35% of HD. S-reactive CD4+ T cells in HD reacted primarily to C-terminal S epitopes, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared to N-terminal epitopes. S-reactive T cell lines generated from SARS-CoV-2-naive HD responded similarly to C-terminal S of human endemic coronaviruses 229E and OC43 and SARS-CoV-2, demonstrating the presence of S-cross-reactive T cells, probably generated during past encounters with endemic coronaviruses. The role of pre-existing SARS-CoV-2 cross-reactive T cells for clinical outcomes remains to be determined in larger cohorts. However, the presence of S-cross-reactive T cells in a sizable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming COVID-19 vaccine trials.
SARS-CoV-2-Reactive T Cells in Healthy Donors and Patients With COVID-19
Nature 2020 Jul 29;[EPub Ahead of Print], J Braun, L Loyal, M Frentsch, D Wendisch, P Georg, F Kurth, S Hippenstiel, M Dingeldey, B Kruse, F Fauchere, E Baysal, M Mangold, L Henze, R Lauster, MA Mall, K Beyer, J Röhmel, S Voigt, J Schmitz, S Miltenyi, I Demuth, MA Müller, A Hocke, M Witzenrath, N Suttorp, F Kern, U Reimer, H Wenschuh, C Drosten, VM Corman, C Giesecke-Thiel, LE Sander, A Thiel