Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion

Tabea M. Eser, Olga Baranov, Manuel Huth, Mohammed I. M. Ahmed, Flora Deák, Kathrin Held, Luming Lin, Kami Pekayvaz, Alexander Leunig, Leo Nicolai, Georgios Pollakis, Marcus Buggert, David A. Price, Raquel Rubio-Acero, Jakob Reich, Philine Falk, Alissa Markgraf, Kerstin Puchinger, Noemi Castelletti, Laura Olbrich, Kanika Vanshylla, Florian Klein, Andreas Wieser, Jan Hasenauer, Inge Kroidl, Michael Hoelscher and Christof Geldmacher ()
Additional contact information
Tabea M. Eser: University Hospital, LMU Munich
Olga Baranov: University Hospital, LMU Munich
Manuel Huth: Helmholtz Zentrum München
Mohammed I. M. Ahmed: University Hospital, LMU Munich
Flora Deák: University Hospital, LMU Munich
Kathrin Held: University Hospital, LMU Munich
Luming Lin: University Hospital, LMU Munich
Kami Pekayvaz: University Hospital, LMU Munich
Alexander Leunig: University Hospital, LMU Munich
Leo Nicolai: University Hospital, LMU Munich
Georgios Pollakis: University of Liverpool
Marcus Buggert: Karolinska Institutet, Karolinska University Hospital Huddinge
David A. Price: Cardiff University School of Medicine, University Hospital, Heath Park
Raquel Rubio-Acero: University Hospital, LMU Munich
Jakob Reich: University Hospital, LMU Munich
Philine Falk: University Hospital, LMU Munich
Alissa Markgraf: University Hospital, LMU Munich
Kerstin Puchinger: University Hospital, LMU Munich
Noemi Castelletti: University Hospital, LMU Munich
Laura Olbrich: University Hospital, LMU Munich
Kanika Vanshylla: Faculty of Medicine and University Hospital Cologne, University of Cologne
Florian Klein: Faculty of Medicine and University Hospital Cologne, University of Cologne
Andreas Wieser: University Hospital, LMU Munich
Jan Hasenauer: Helmholtz Zentrum München
Inge Kroidl: University Hospital, LMU Munich
Michael Hoelscher: University Hospital, LMU Munich
Christof Geldmacher: University Hospital, LMU Munich

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Despite intensive research since the emergence of SARS-CoV-2, it has remained unclear precisely which components of the early immune response protect against the development of severe COVID-19. Here, we perform a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We find that soluble and transcriptional markers of systemic inflammation peak during the first week after symptom onset and correlate directly with upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4+ and CD8+ T cells correlate inversely with various inflammatory markers and UA-VLs. In addition, we show that high frequencies of activated CD4+ and CD8+ T cells are present in acutely infected nasopharyngeal tissue, many of which express genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of IFNG mRNA-expressing CD4+ and CD8+ T cells in the infected epithelium is further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identify an immune correlate of protection against SARS-CoV-2, which could inform the development of more effective vaccines to combat the acute and chronic illnesses attributable to COVID-19.

Date: 2023
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DOI: 10.1038/s41467-023-38020-8

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