Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19
Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19
复制标题
DOI：
10.1093/infdis/jiab065
复制
发表时间：
2021-03-22
影响因子：
6.4
通讯作者：
van de Veerdonk, Frank L.
中科院分区：
文献类型：
--
作者：
Janssen, Nico A. F.;Grondman, Inge;van de Veerdonk, Frank L.
新冠肺炎的临床谱系各不相同，这种变异的宿主反应的差异还没有完全阐明。新冠肺炎病的严重程度与过度的促炎免疫反应和严重的淋巴细胞减少有关。通过对14 7例新冠肺炎患者的血浆细胞因子测定和蛋白质组学分析，探讨炎症反应与疾病严重程度的关系。外周血单核细胞细胞因子产生实验和全血流式细胞仪检测。结果证实了高炎性先天免疫状态，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。聚类分析显示新冠肺炎患者中没有特定的炎性内分泌类型。功能分析显示危重病患者的适应性细胞因子(干扰素-γ、白介素17和白介素n-22)的产生和显著的T细胞耗竭，而先天免疫反应是完整的或高反应性的。总而言之，这一广泛的分析提供了对严重到危重新冠肺炎的病理生物学的全面洞察，并强调了疾病严重性的潜在生物标志物。
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.