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)
(2023)
Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion.
NATURE COMMUNICATIONS, 14 (1).
2952-.
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<sup>+</sup> and CD8<sup>+</sup> T cells correlate inversely with various inflammatory markers and UA-VLs. In addition, we show that high frequencies of activated CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> 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 |
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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: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173434 |