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

Eser, Tabea M., Baranov, Olga, Huth, Manuel, Ahmed, Mohammed I. M., Deák, Flora, Held, Kathrin, Lin, Luming, Pekayvaz, Kami, Leunig, Alexander, Nicolai, Leo, Pollakis, Georgios, Buggert, Marcus, Price, David A. ORCID:, Rubio-Acero, Raquel, Reich, Jakob, Falk, Philine, Markgraf, Alissa, Puchinger, Kerstin, Castelletti, Noemi, Olbrich, Laura, Vanshylla, Kanika, Klein, Florian, Wieser, Andreas, Hasenauer, Jan, Kroidl, Inge, Hoelscher, Michael and Geldmacher, Christof 2023. Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion. Nature Communications 14 (1) , 2952. 10.1038/s41467-023-38020-8

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 25 May 2023
Date of Acceptance: 12 April 2023
Last Modified: 11 Oct 2023 20:42

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