Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.
J Infect Dis. 2021 Apr 23;223(8):1322-1333. doi: 10.1093/infdis/jiab065.
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.
新型冠状病毒疾病的临床谱变化多样，宿主反应的差异尚未完全阐明。新型冠状病毒疾病的严重程度与过度的促炎免疫反应和明显的淋巴细胞减少有关。通过对 147 例新型冠状病毒疾病患者的血浆细胞因子测量和蛋白质组学分析，研究了根据疾病严重程度的炎症反应。此外，还进行了外周血单核细胞细胞因子产生测定和全血流式细胞术。结果证实了一种过度的先天免疫状态，同时强调了肝细胞生长因子和干细胞因子作为疾病严重程度的潜在生物标志物。聚类分析显示，新型冠状病毒疾病患者没有特定的炎症表型。功能分析显示，危重症患者适应性细胞因子（干扰素-γ、白细胞介素-17 和白细胞介素-22）的产生受到抑制，T 细胞衰竭明显，而先天免疫反应完整或过度反应。总的来说，这项广泛的分析提供了对严重至危重新冠病毒疾病的病理生物学的全面了解，并强调了疾病严重程度的潜在生物标志物。
