4.7 Article

Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19

期刊

JOURNAL OF INFECTIOUS DISEASES
卷 223, 期 8, 页码 1322-1333

出版社

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab065

关键词

COVID-19; disease severity; biomarkers; cytokines; proteomics; innate immunity; adaptive immunity; flow cytometry; exhaustion markers

资金

  1. Netherlands Organisation for Health Research and Development (ZonMw) [10430 01 201 0002]

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The study conducted plasma cytokine measurements and proteomics analysis on 147 COVID-19 patients, uncovering a hyperinflammatory innate immune state and potential biomarkers. It revealed T-cell exhaustion in critically ill patients, with intact or hyperresponsive innate immune responses.
The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-y, interleukin-17, and interleuki n-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity.

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