SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.

Braun, Julian; Loyal, Lucie; Frentsch, Marco; Wendisch, Daniel; Georg, Philipp; Kurth, Florian; Hippenstiel, Stefan; Dingeldey, Manuela; Kruse, Beate; Fauchere, Florent; Baysal, Emre; Mangold, Maike; Henze, Larissa; Lauster, Roland; Mall, Marcus A; Beyer, Kirsten; Röhmel, Jobst; Voigt, Sebastian; Schmitz, Jürgen; Miltenyi, Stefan; Demuth, Ilja; Müller, Marcel A; Hocke, Andreas; Witzenrath, Martin; Suttorp, Norbert; Kern, Florian; Reimer, Ulf; Wenschuh, Holger; Drosten, Christian; Corman, Victor M; Giesecke-Thiel, Claudia; Sander, Leif Erik; Thiel, Andreas

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.