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

• Julian Braun^1,2 na1,
• Lucie Loyal^1,2 na1,
• Marco Frentsch^3 na1,
• Daniel Wendisch  ORCID: orcid.org/0000-0003-1968-5751⁴,
• Philipp Georg⁴,
• Florian Kurth  ORCID: orcid.org/0000-0002-3807-473X^4,5,
• Stefan Hippenstiel  ORCID: orcid.org/0000-0002-5146-1064⁴,
• Manuela Dingeldey^1,2,
• Beate Kruse^1,2,
• Florent Fauchere  ORCID: orcid.org/0000-0002-1955-6362^1,2,
• Emre Baysal^1,2,
• Maike Mangold^1,2,
• Larissa Henze^1,2,
• Roland Lauster^1,6,
• Marcus A. Mall^7,13,
• Kirsten Beyer⁷,
• Jobst Röhmel⁷,
• Sebastian Voigt  ORCID: orcid.org/0000-0003-1544-9903⁸,
• Jürgen Schmitz⁹,
• Stefan Miltenyi⁹,
• Ilja Demuth¹⁰,
• Marcel A. Müller  ORCID: orcid.org/0000-0003-2242-5117¹¹,
• Andreas Hocke⁴,
• Martin Witzenrath⁴,
• Norbert Suttorp⁴,
• Florian Kern  ORCID: orcid.org/0000-0002-0368-8408^12,13,
• Ulf Reimer¹²,
• Holger Wenschuh¹²,
• Christian Drosten  ORCID: orcid.org/0000-0001-7923-0519^11,14,
• Victor M. Corman  ORCID: orcid.org/0000-0002-3605-0136¹¹,
• Claudia Giesecke-Thiel  ORCID: orcid.org/0000-0002-5927-7018^15 na2,
• […]
• Leif Erik Sander  ORCID: orcid.org/0000-0002-0476-9947^4 na2 &
• Andreas Thiel  ORCID: orcid.org/0000-0002-5515-4002^1,2 na2

PDF: https://www.nature.com/articles/s41586-020-2598-9_reference.pdf

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.

https://www.nature.com/articles/s41586-020-2598-9