新型冠状病毒2型疫苗接种后的中枢神经系统免疫相关疾病：一项多中心研究。
Central nervous system immune-related disorders after SARS-CoV-2 vaccination: a multicenter study.
作者信息
Vogrig Alberto, Tartaglia Sara, Dentoni Marta, Fabris Martina, Bax Francesco, Belluzzo Marco, Verriello Lorenzo, Bagatto Daniele, Gastaldi Matteo, Tocco Pierluigi, Zoccarato Marco, Zuliani Luigi, Pilotto Andrea, Padovani Alessandro, Villagrán-García Macarena, Davy Vincent, Gigli Gian Luigi, Honnorat Jérôme, Valente Mariarosaria
机构信息
Department of Medicine (DMED), University of Udine, Udine, Italy.
Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy.
出版信息
Front Immunol. 2024 Feb 5;15:1344184. doi: 10.3389/fimmu.2024.1344184. eCollection 2024.
BACKGROUND
COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination.
METHODS
Multicenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis.
RESULTS
Nineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2.
CONCLUSION
CNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.
背景
由于新冠病毒疫苗具有出色的安全性和有效性数据，已获批准使用，其应用也有助于减少新冠病毒的神经并发症。然而，临床试验检测罕见不良事件的能力不足。在此，目的是描述新冠病毒疫苗接种后中枢神经系统（CNS）免疫相关事件的临床谱和免疫学特征。
方法
多中心、回顾性队列研究（2020年12月1日至2022年4月30日）。纳入标准为：（1）新冠病毒疫苗接种后发生的中枢神经系统疾病（根据2021年巴特勒标准可能存在因果关系）；（2）根据以下标准有免疫介导病因的证据：（i）2016年Graus自身免疫性脑炎（AE）标准；（ii）2015年Wingerchuk视神经脊髓炎谱系障碍标准；（iii）脊髓炎标准。
结果
在意大利和法国的7家三级转诊医院（其中一家是AE国家转诊中心）纳入了19例患者，研究历时近一年半的疫苗接种活动。所接种的疫苗中，基于mRNA的占63%，腺病毒载体的占37%。接种疫苗至症状出现的中位时间为14天（范围：2 - 41天）。74%的患者脑脊液呈炎性；5%检测到自身抗体。脑脊液细胞因子分析（n = 3）显示CXCL - 10（IP - 10）升高，提示T细胞强烈激活。患者患有AE（58%）、脊髓炎（21%）、急性播散性脑脊髓炎（ADEM）（16%）和脑干脑炎（5%）。除2例患者外，所有患者均接受了免疫调节治疗。在最后一次随访时（中位时间130天；范围：32 - 540天），只有1例患者（5%）改良Rankin量表评分>2分。
结论
即使在转诊中心，新冠病毒疫苗接种后的中枢神经系统不良事件似乎也非常罕见，主要包括抗体阴性的AE、脊髓炎和接种疫苗约2周后发生的ADEM。大多数患者经免疫调节治疗后病情改善。
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