新冠后神经系统表现与神经炎症、自身抗体负荷增加及持续性补体激活相关。
Post-COVID neurological manifestations are associated with neuroinflammation, increased autoantibody burden, and persistent complement activation.
文献信息
| PMID | 42945604 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | João Victor Carvalho de Deus |
| 作者单位 | Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. |
| 期刊 | Journal of neuroimmunology |
| SCI 分区 | Q3 |
| IF | 2.8 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 神经系统表现是新冠后状况（PCC）常见的持续特征，但其发病机制尚不清楚。方法：本研究纳入神经-PCC参与者（n=29，主要表现为持续性头痛、疲劳、睡眠障碍、嗅觉丧失/味觉障碍、认知主诉和/或感觉异常）、从COVID-19康复者（n=32）以及未感染对照（n=32），三组性别和年龄匹配。采集急性期（0-14天）和两个恢复期时间点（3-6个月和9-12个月）的配对血清样本，采用Luminex法检测抗核抗体（ANA）、抗可提取核抗原（ENA）抗体、抗中性粒细胞胞质抗体（ANCA）以及抗细胞因子自身抗体。采用Ella ELISA定量神经炎症生物标志物，包括神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）、总Tau蛋白和神经颗粒素，并通过C5b-9水平升高判定补体激活。结果：神经-PCC患者在急性期表现出更多神经系统症状，头痛和疲劳频率更高，并且肥胖和心血管合并症的患病率更高。GFAP在感染后长达一年内持续升高，且与症状持续无关。然而，只有神经-PCC患者在急性期出现NfL水平的一过性升高，并在整个随访期间持续存在补体激活。没有特定自身抗体与神经-PCC相关，但这些患者表现出更高的累积自身抗体负荷。多变量logistic回归分析显示，住院和急性期神经系统负担与神经-PCC相关，而抗细胞因子自身抗体计数呈反向趋势。结论：补体激活增加和自身抗体负荷升高提示广泛且非特异性的免疫激活，可能促成持续性低度神经炎症状态，从而可能驱动COVID-19后神经系统症状的持续存在。
英文摘要
Neurological manifestations represent commonly persistent features of post-COVID conditions (PCC), but mechanisms underlying their pathogenesis remain unclear. In this study, participants with neuro-PCC (n = 29), mostly presenting with persistent headache, fatigue, sleep disturbances, anosmia/dysgeusia, cognitive complaints, and/or paresthesia, recovered from COVID-19 (n = 32), and non-infected controls (n = 32), all matched for sex and age, had paired serum samples from acute phase (0-14 days) and two time points of convalescence (3-6 months and 9-12 months) assessed for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), antineutrophil cytoplasmic antibodies (ANCA), and autoantibodies against cytokines using Luminex assays. Biomarkers of neuroinflammation, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total Tau protein, and neurogranin were quantified by Ella ELISA and complement activation was determined by increased C5b-9 levels. Patients with neuro-PCC showed a greater number of neurological symptoms during acute phase, with increased frequency of headache and fatigue, and a higher prevalence of obesity and cardiovascular comorbidities. GFAP remained elevated for up to one year after infection, independently of symptom persistence. However, only patients with neuro-PCC exhibited a transient increase in NfL levels during acute phase, and persistent complement activation throughout follow-up. No specific autoantibody was associated with neuro-PCC, but these patients exhibited a higher cumulative autoantibody burden. Multivariable logistic regression analysis showed that hospitalization and the neurological burden during the acute phase were associated with neuro-PCC, whereas anti-cytokine autoantibody counts showed an inverse trend. Increased complement activation and a higher autoantibody burden suggest a broad and nonspecific immune activation that may contribute to a sustained low-grade neuroinflammatory state, potentially driving the persistence of neurological symptoms after COVID-19.