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

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Eser, Tabea M, Baranov, Olga, Huth, Manuel, Ahmed, Mohammed IM, Deak, Flora, Held, Kathrin, Lin, Luming, Pekayvaz, Kami, Leunig, Alexander, Nicolai, Leo et al (show 17 more authors) , Pollakis, Georgios ORCID: 0000-0002-9659-5461, Buggert, Marcus, Price, David A, 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-.

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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.

Item Type:	Article
Uncontrolled Keywords:	CD8-Positive T-Lymphocytes, Humans, Nucleocapsid, Seroconversion, COVID-19, SARS-CoV-2
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	05 Oct 2023 08:55
Last Modified:	05 Oct 2023 09:01
DOI:	10.1038/s41467-023-38020-8
Open Access URL:	https://doi.org/10.1038/s41467-023-38020-8
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173434