SARS-CoV-2感染后嗅黏膜中α-突触核蛋白种子活性的患病率：一项初步研究的结果。

文献信息

中文摘要

背景： 嗅觉功能障碍（OD）是SARS-CoV-2感染的标志性表现，据认为其源于病毒经嗅黏膜（OM）侵入所诱导的神经炎症。嗅觉减退也影响大多数帕金森病（PD）患者，在PD中由嗅觉系统的α-突触核蛋白（aSyn）病理所致，并且可使用aSyn种子扩增试验（aSyn-SAA）在OM中检测到aSyn种子活性。本初步研究旨在使用aSyn-SAA探讨SARS-CoV-2感染是否在OM样本中诱导局部aSyn错误折叠和聚集。方法：我们开展了一项观察性研究，纳入PD患者（n=51）、有 documented 症状性SARS-CoV-2感染史的个体（post-COVID；n=95）和健康对照（HC；n=42）。post-COVID参与者根据持续性OD（COVID+OD；n=42）或嗅觉正常（COVID-OD；n=53）使用Sniffin'-Sticks识别（SSI）和辨别（SSD）测试进行分层。OM样本由耳鼻喉科专家获取，并在维罗纳大学通过aSyn-SAA进行分析。临床表型分析包括MDS-UPDRS、MoCA和Innsbruck-RBD量表。结果：OM-SAA阳性率在PD与post-COVID参与者及HC之间显著不同（80.4% vs 24.2% vs 11.9%；p<0.001）。在post-COVID组内，COVID+OD的阳性率高于COVID-OD（35.7% vs 15.1%；p=0.030），且COVID+OD与HC不同（p=0.030），而COVID-OD则无差异（p=0.65）。在post-COVID参与者中，aSyn-SAA阳性与较低的SSI（p=0.007）和SSD（p<0.001）评分相关，但与MDS-UPDRS、MoCA或RBD指标无关。OM-SAA阳性在持续性post-COVID-OD个体中富集，并与嗅觉损害相关。结论：这些发现支持以下假说：SARS-CoV-2感染后的神经炎症可能促进局部aSyn聚集。OM-SAA阳性的生物学和预后相关性尚不清楚，需要进一步的前瞻性研究。

英文摘要

Olfactory dysfunction (OD) is a hallmark of SARS-CoV-2-infection where it is believed to result from neuroinflammation induced by viral invasion via the olfactory mucosa (OM). Hyposmia also affects the majority of patients with Parkinson's disease (PD) where it is caused by α-synuclein (aSyn) pathology in the olfactory system, and aSyn-seeding-activity can be detected in the OM using aSyn-seeding-amplification-assays (aSyn-SAA). The present pilot study aimed to investigate whether SARS-CoV-2-infection induces local aSyn-misfolding and -aggregation in OM samples using aSyn-SAA. We conducted an observational study including PD patients (n = 51), individuals with a history of documented symptomatic SARS-CoV-2-infection (post-COVID; n = 95), and healthy controls (HC; n = 42). Post-COVID-participants were stratified based on persistent OD (COVID+OD; n = 42) or normal olfaction (COVID-OD; n = 53) using Sniffin'-Sticks-Identification (SSI) and -Discrimination (SSD) tests. OM samples were obtained by ENT specialists and analyzed by aSyn-SAA at the University of Verona. Clinical phenotyping included MDS-UPDRS, MoCA, and the Innsbruck-RBD-Inventory. OM-SAA positivity rates were significantly different between PD and both post-COVID-participants and HCs (80.4% vs 24.2% vs 11.9%; p < 0.001). Within the post-COVID-group, positivity rates were higher in COVID+OD vs COVID-OD (35.7% vs 15.1%; p = 0.030), and COVID+OD differed from HC (p = 0.030), while COVID-OD did not (p = 0.65). Among post-COVID-participants, aSyn-SAA positivity was associated with lower SSI (p = 0.007) and SSD (p < 0.001) scores, but not with MDS-UPDRS, MoCA, or RBD measures. OM-SAA-positivity was enriched among individuals with persistent post-COVID-OD and correlated with olfactory impairment. These findings support the hypothesis that neuroinflammation following SARS-COV-2-infection might promote local aSyn-aggregation. The biological and prognostic relevance of OM-SAA positivity is unknown and needs further prospective investigation.