Abstract
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-γ, interleukin-17, and interleukin-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.
Keywords: COVID-19; adaptive immunity; biomarkers; cytokines; disease severity; exhaustion markers; flow cytometry; innate immunity; proteomics.
【저자키워드】 COVID-19, Adaptive immunity, proteomics, Biomarkers, Cytokines, Innate immunity, disease severity, flow cytometry, exhaustion markers, 【초록키워드】 Adaptive immunity, proteomics, immune response, Biomarkers, Cytokines, innate immune response, adaptive, Inflammatory responses, Innate immunity, disease severity, Variation, interferon, cytokine, host response, flow cytometry, COVID-19 disease, Peripheral blood, lymphopenia, proinflammatory, interleukin, Critically ill, Whole blood, immune responses, response, disease, Critical, T-cell exhaustion, hepatocyte growth factor, critically ill patients, cytokine production, COVID-19 patients, Potential biomarker, innate immune, Analysis, Inflammatory, stem cell, stem cell factor, mononuclear cell, interferon-γ, interleukin-17, Clustering analysis, COVID-19 disease severity, potential biomarkers, innate immune responses, Plasma cytokine, Hyperinflammatory, Cell, highlight, Result, performed, provide, abrogated, highlighting, 【제목키워드】 response, Innate,