Chen Jiaxin, Zhou Wenkai, Cen Mengting, Chen Can, Cao Kexin, Chen Mengsha, Qu Rongrong, Miao Jiani, Qi Jiaxing, Wu Xiaoyue, Zhang Huihui, Feng Qianqian, Dai Anqi, Zhou Jingtong, Xu Nani, Hu Xiaowei, Yang Shigui
Department of Emergency Medicine of Second Affiliated Hospital, and, Department of Epidemiology and Biostatistics, School of Public Health and The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, China.
Xihu District Center for Disease Control and Prevention, Xihu District Health Inspection), Hangzhou, 310007, Zhejiang, China.
J Neurol. 2025 Jul 10;272(8):499. doi: 10.1007/s00415-025-13238-2.
Previous studies have highlighted potential associations between influenza vaccination (IV) and neurological outcomes, particularly neurodegenerative disorders (NDs) and demyelinating disorders (DDs). However, the existing evidence remains inconclusive. Given the widespread global uptake of IV, even small potential effects may carry important public health implications. Therefore, a comprehensive synthesis of current evidence is essential to clarify these associations and inform evidence-based vaccination strategies.
This study aimed to systematically examine the associations between IV and NDs as well as DDs.
We systematically searched PubMed, Embase, Scopus, and Web of Science from database inception to November 30, 2024, to identify relevant studies. Studies meeting predefined were selected for analysis, followed by data extraction and quality assessment. Pooled odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed by population characteristics and study features, and sensitivity analyses were conducted to test the robustness of results.
A total of 64 studies were included in the analysis (22 on NDs and 44 on DDs), comprising 5,679,964,431 participants were included. IV was associated with a reduced risk of NDs (OR = 0.85, 95% CI 0.75-0.98). Subgroup analyses showed a stronger protective effect against NDs among individuals with chronic comorbidities (OR = 0.66, 95% CI 0.63-0.69) and older adults (OR = 0.83, 95% CI 0.69-0.99), with the protective effect increasing with age. For DDs, IV was associated with an increased risk of DDs (OR = 1.61, 95% CI 1.22-2.12). Elevated risks were primarily observed in earlier studies (OR = 2.15, 95% CI 1.23-3.77) and in populations who received pandemic influenza vaccines (OR = 2.03, 95% CI 1.44-2.86). However, no statistically significant association between influenza vaccination and DDs was found in studies conducted after 2010 (OR = 1.13, 95% CI 0.90-1.41). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected.
IV was associated with a reduced risk of NDs, particularly among older adults and individuals with chronic comorbidities. Although an increased risk of DDs was observed in earlier studies and among recipients of pandemic IV, no significant association was found in studies conducted over the past decade. Given the protective benefits of IV against both influenza itself and NDs in elderly individuals and those with chronic health conditions, expanding IV coverage in these vulnerable groups is strongly recommended.
先前的研究强调了流感疫苗接种（IV）与神经学结局之间的潜在关联，特别是神经退行性疾病（NDs）和脱髓鞘疾病（DDs）。然而，现有证据仍不确凿。鉴于全球范围内流感疫苗接种的广泛普及，即使是微小的潜在影响也可能具有重要的公共卫生意义。因此，全面综合当前证据对于阐明这些关联并为基于证据的疫苗接种策略提供信息至关重要。
本研究旨在系统地研究流感疫苗接种与神经退行性疾病以及脱髓鞘疾病之间的关联。
我们从数据库建立至2024年11月30日，系统地检索了PubMed、Embase、Scopus和Web of Science，以识别相关研究。选择符合预定义标准的研究进行分析，随后进行数据提取和质量评估。使用随机效应模型计算合并比值比（ORs）和95%置信区间（CIs）。按人群特征和研究特征进行亚组分析，并进行敏感性分析以检验结果的稳健性。
共有64项研究纳入分析（22项关于神经退行性疾病，44项关于脱髓鞘疾病），纳入了5,679,964,431名参与者。流感疫苗接种与神经退行性疾病风险降低相关（OR = 0.85，95% CI 0.75 - 0.98）。亚组分析显示，在患有慢性合并症的个体（OR = 0.66，95% CI 0.63 - 0.69）和老年人（OR = 0.83，95% CI 0.69 - 0.99）中，对神经退行性疾病的保护作用更强，且保护作用随年龄增加而增强。对于脱髓鞘疾病，流感疫苗接种与脱髓鞘疾病风险增加相关（OR = 1.61，95% CI 1.22 - 2.12）。风险升高主要在早期研究中观察到（OR = 2.15，95% CI 1.23 - 3.77）以及在接种大流行性流感疫苗的人群中（OR = 2.03，95% CI 1.44 - 2.86）。然而，在2010年后进行的研究中未发现流感疫苗接种与脱髓鞘疾病之间存在统计学显著关联（OR = 1.13，95% CI 0.90 - 1.41）。敏感性分析证实了这些发现的稳健性，且未检测到显著的发表偏倚。
流感疫苗接种与神经退行性疾病风险降低相关，特别是在老年人和患有慢性合并症的个体中。尽管在早期研究以及大流行性流感疫苗接种者中观察到脱髓鞘疾病风险增加，但在过去十年进行的研究中未发现显著关联。鉴于流感疫苗接种对老年人和患有慢性健康状况者预防流感本身以及神经退行性疾病均有益处，强烈建议在这些弱势群体中扩大流感疫苗接种覆盖范围。
