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Early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion (preprint)
researchsquare; 2022.
Preprint
in English
| PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2222184.v1
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. To address this issue, we performed a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We found that soluble and transcriptional markers of systemic inflammation peaked during the first week after symptom onset and correlated directly with the upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4+ and CD8+ T cells correlated inversely with various inflammatory markers and UA-VLs. In addition, we observed high frequencies of activated CD4+ and CD8+ T cells in acutely infected nasopharyngeal tissue, many of which expressed genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of functionally active T cells in the infected epithelium was further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identified 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.
Full text:
Available
Collection:
Preprints
Database:
PREPRINT-RESEARCHSQUARE
Main subject:
COVID-19
/
Inflammation
Language:
English
Year:
2022
Document Type:
Preprint
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