新型冠状病毒肺炎(COVID-19)后并发症和神经表现的特征分析和生物标志物分析。
Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations.
机构信息
Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA 94121, USA.
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA.
出版信息
Cells. 2021 Feb 13;10(2):386. doi: 10.3390/cells10020386.
As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.
随着 SARS-CoV-2 大流行的持续,有报道表明 COVID-19 康复后会出现神经系统后遗症。目前尚不清楚解释长期神经系统后遗症的机制,需要加以确定。采集了 24 名在初次感染后 1 至 3 个月内从 COVID-19 中康复的个体的血浆,用于细胞因子和抗体水平以及富含神经元的细胞外囊泡 (nEV) 蛋白货物分析。所有 COVID-19 参与者的血浆细胞因子 IL-4 均增加。有自我报告的神经系统问题的志愿者 (nCoV, = 8) 的 IL6 与年龄或后遗症的严重程度呈正相关,至少有一种合并症且 SARS-CoV-2 抗体水平高于无神经系统问题的 COVID-19 个体 (CoV, = 16)。来自所有 COVID-19 康复个体的 nEV 中的神经功能障碍的蛋白质标志物,包括淀粉样蛋白β、神经丝轻链、神经颗粒蛋白、总 tau 和 p-T181-tau,均显著高于历史对照组。这项研究表明 COVID-19 感染后持续存在外周和神经炎症,可能通过改变 nEV 蛋白影响神经系统后遗症。从 COVID-19 中康复的个体可能存在隐匿性神经损伤,而那些有明显神经系统症状的个体则感染更为严重。需要进行纵向研究来监测血浆生物标志物和 nEV 货物,以评估持续的神经退行性变和全身影响。