Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage
Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage
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DOI：
10.15252/embj.2020105896
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发表时间：
2020-12-14
期刊：
影响因子：
11.4
通讯作者：
Zhang, Yong-Zhen
中科院分区：
文献类型：
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作者：
Chen, Yan-Mei;Zheng, Yuanting;Zhang, Yong-Zhen
COVID-19的特征是免疫反应失调、代谢功能障碍和对多个器官功能的不利影响。为了了解宿主对COVID-19病理生理学的反应，我们结合转录组学、蛋白质组学和代谢组学，在66名经历一系列疾病严重程度的COVID-19感染患者和17名健康对照的外周血和血浆样本中鉴定分子标志物。大量表达的基因、蛋白质、代谢物和细胞外RNA（exRNA）表现出与各种临床参数的强关联。多组组织特异性蛋白质和exRNA在轻度和重度患者中显著变化，表明对组织功能的潜在影响。在严重疾病进展的患者中观察到中性粒细胞的慢性活化、IFN-I信号传导和高水平的炎性细胞因子。相比之下，经历较轻疾病症状的COVID-19感染患者显示出强大的T细胞反应。最后，我们确定了基因、蛋白质和exRNA作为可能有助于预测SARS-CoV-2感染预后的潜在生物标志物。这些数据完善了我们对COVID-19的病理生理学和临床进展的理解。概要蛋白质组学、代谢组学和RNAseq数据绘制了不同疾病严重程度的COVID-19患者的免疫反应，揭示了与疾病进展和组织特异性蛋白质改变相关的分子标志物。在66名临床诊断和实验室确认的COVID-19患者和17名未感染对照中对SARS-CoV 2感染的宿主反应的多组学分析。多组学数据与关键临床参数之间的显著相关性。组织特异性蛋白质和exRNA的改变。免疫反应的增强激活与COVID-19发病机制有关。预测COVID-19临床结果的生物标志物作为前瞻性标志物等待临床验证。
COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.SYNOPSISimageProteomics, metabolomics and RNAseq data map immune responses in COVID-19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue-specific proteins. A multi-omics profiling of the host response to SARS-CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID-19 patients and 17 uninfected controls. Significant correlations between multi-omics data and key clinical parameters. Alteration of tissue-specific proteins and exRNAs. Enhanced activation of immune responses is associated with COVID-19 pathogenesis. Biomarkers to predict COVID-19 clinical outcomes pending clinical validation as prospective marker.