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

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Nature


. 2020 Jul 29.
doi: 10.1038/s41586-020-2598-9. Online ahead of print.
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19


Julian Braun ^{1 2} , Lucie Loyal ^{1 2} , Marco Frentsch ³ , Daniel Wendisch ⁴ , Philipp Georg ⁴ , Florian Kurth ^{4 5} , Stefan Hippenstiel ⁴ , Manuela Dingeldey ^{1 2} , Beate Kruse ^{1 2} , Florent Fauchere ^{1 2} , Emre Baysal ^{1 2} , Maike Mangold ^{1 2} , Larissa Henze ^{1 2} , Roland Lauster ^{1 6} , Marcus A Mall ^{7 8} , Kirsten Beyer ⁷ , Jobst R?hmel ⁷ , Sebastian Voigt ⁹ , J?rgen Schmitz ¹⁰ , Stefan Miltenyi ¹⁰ , Ilja Demuth ¹¹ , Marcel A M?ller ¹² , Andreas Hocke ⁴ , Martin Witzenrath ⁴ , Norbert Suttorp ⁴ , Florian Kern ^{13 8} , Ulf Reimer ¹³ , Holger Wenschuh ¹³ , Christian Drosten ^{12 14} , Victor M Corman ¹² , Claudia Giesecke-Thiel ¹⁵ , Leif Erik Sander ¹⁶ , Andreas Thiel ^{17 18}



Affiliations

• PMID: 32726801
• DOI: 10.1038/s41586-020-2598-9

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic^1,2. 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.