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一种新型高效肽组学工作流程揭示了轻症和多次感染新冠病毒康复患者血浆肽组的长期失调。

Long-term dysregulation of plasma peptidome in mild and multiple COVID-19 recovered patients revealed by a novel efficient peptidomics workflow.

作者信息

Song Zhijing, Liu Chaoran, Liu Yaozhou, Bian Zheng, Sun Qing, He Ting, Su Rong, Huang Shengchun, Dai Ningbin, Zhao Ke Li, Li Yan, Liang Kai

机构信息

Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Western Institute of Health Data Science, Chongqing, 400050, China.

出版信息

Anal Bioanal Chem. 2025 Feb;417(4):733-746. doi: 10.1007/s00216-024-05684-0. Epub 2024 Dec 7.

DOI:10.1007/s00216-024-05684-0
PMID:39644382
Abstract

After recovering from COVID-19, many patients experience "long COVID" symptoms. Existing research has predominantly focused on moderate to severe cases, with limited studies examining mild cases and recurrent infections. The circulating low-molecular-weight (LMW) peptidome, involving lipid metabolism, coagulation, and immune pathways, is crucial for understanding COVID-19's long-term effects. We developed a peptidomics workflow utilizing solid-phase extraction with highly wrinkled GO-FeO composite materials (HWGO-F) and nanoLC-MS/MS detection. By altering the pH, HWGO-F enhances plasma peptide adsorption and purification. Compared to traditional methods, our workflow offers improved detection depth and reproducibility for over 70% of peptide signals with CV < 20%. We investigated plasma peptide profiles in mild COVID-19 patients post-recovery from single or second infections. The findings indicate persistent abnormalities in initial COVID-19 infections' plasma peptide profiles, gradually diminishing over time. Secondary infections prolong recovery. Disrupted functions include lipid metabolism, coagulation and complement cascades, and infection-related pathways. Lipid metabolism may normalize within 3 months, while coagulation and immune abnormalities can last 3-6 months. After secondary infections, lipid metabolism irregularities may last at least 1 month, with extended coagulation and immune imbalances. These results provide a theoretical foundation for understanding the widespread occurrence of long COVID and guide recovery care for mild cases.

摘要

新冠病毒感染康复后,许多患者会出现“长期新冠”症状。现有研究主要聚焦于中重症病例,对轻症病例和复发性感染的研究有限。涉及脂质代谢、凝血和免疫途径的循环低分子量(LMW)肽组对于理解新冠病毒的长期影响至关重要。我们开发了一种肽组学工作流程,利用具有高度褶皱的氧化石墨烯-氧化亚铁复合材料(HWGO-F)进行固相萃取,并采用纳升液相色谱-串联质谱检测。通过改变pH值,HWGO-F可增强血浆肽的吸附和纯化。与传统方法相比,我们的工作流程对70%以上的肽信号具有更高的检测深度和重现性,变异系数(CV)<20%。我们研究了轻症新冠病毒感染患者单次或二次感染康复后的血浆肽谱。研究结果表明,初次新冠病毒感染的血浆肽谱存在持续异常,且随时间逐渐减弱。二次感染会延长康复时间。受影响的功能包括脂质代谢、凝血和补体级联反应以及与感染相关的途径。脂质代谢可能在3个月内恢复正常,而凝血和免疫异常可能持续3至6个月。二次感染后,脂质代谢异常可能至少持续1个月,凝血和免疫失衡会持续更长时间。这些结果为理解“长期新冠”的广泛发生提供了理论基础,并为轻症病例的康复护理提供了指导。

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