Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

Autor: Akshay Binayke, Aymaan Zaheer, Jyotsna Dandotiya, Sonu Kumar Gupta, Shailendra Mani, Manas Ranjan Tripathy, Upasna Madan, Tripti Shrivastava, Yashwant Kumar, Anil Kumar Pandey, Deepak Kumar Rathore, Amit Awasthi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Vaccines, Vol 10, Iss 10, p 1762 (2022)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines10101762
Popis: The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0–3, 7–9, and 14–16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1β, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response.
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