Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome.

IF 2.5 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Harry Alexopoulos, Martina Samiotaki, Eirini Gkogkou, Sofia Mavromati, Kleopatra Bitzogli, Georgios Panagiotou, Athanasios Tzioufas, Eleni Magira, Αnastasia Kotanidou, Ioannis Trougakos
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Abstract

Purpose: Coronavirus disease 2019 (COVID-19) has highlighted significant neurological complications in severe cases. Cerebrospinal fluid (CSF) proteomics could reveal biomarkers related to clinical outcome among critically ill patients.

Experimental design: We performed high-resolution proteomic analyses of CSF samples from 29 intensive care unit (ICU) patients with severe COVID-19 and 19 controls. Differentially expressed proteins and associated pathways were identified through bioinformatic and statistical analyses.

Results: Proteomic analysis identified 488 significantly altered proteins between COVID-19 patients and controls. Proteins linked to coagulation, inflammation, and blood-brain barrier dysfunction (e.g., SERPINC1, KNG1, PLG) were elevated in patients who survived ICU admission. Conversely, proteins associated with metabolic disruption, cellular stress, and neuroinflammation (e.g., FABP3, PDIA4) were upregulated in non-survivors. Pathway enrichment analyses confirmed involvement of immune activation, inflammatory responses, and coagulation cascades.

Conclusions and clinical relevance: CSF proteomics in severe COVID-19 patients reveals potential biomarkers predictive of patient outcomes. These findings support the involvement of systemic inflammation and blood-brain barrier disruption in COVID-19 pathophysiology, suggesting novel targets for personalized intervention strategies.

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重症COVID-19患者脑脊液的蛋白质组学分析揭示了与疾病结局相关的预后生物标志物
目的:2019冠状病毒病(COVID-19)在重症病例中突出了显著的神经系统并发症。脑脊液(CSF)蛋白质组学可以揭示危重患者临床预后相关的生物标志物。实验设计:我们对29名重症COVID-19患者和19名对照组的脑脊液样本进行了高分辨率蛋白质组学分析。通过生物信息学和统计学分析鉴定了差异表达蛋白和相关途径。结果:蛋白质组学分析发现,在COVID-19患者和对照组之间存在488个显著改变的蛋白质。在ICU住院存活的患者中,与凝血、炎症和血脑屏障功能障碍相关的蛋白(如serpin1、KNG1、PLG)升高。相反,与代谢破坏、细胞应激和神经炎症相关的蛋白质(如FABP3、PDIA4)在非幸存者中上调。途径富集分析证实了免疫激活、炎症反应和凝血级联反应的参与。结论和临床意义:重症COVID-19患者CSF蛋白质组学揭示了预测患者预后的潜在生物标志物。这些发现支持了系统性炎症和血脑屏障破坏参与COVID-19病理生理学,为个性化干预策略提供了新的目标。
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来源期刊
PROTEOMICS – Clinical Applications
PROTEOMICS – Clinical Applications 医学-生化研究方法
CiteScore
5.20
自引率
5.00%
发文量
50
审稿时长
1 months
期刊介绍: PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.
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