Hema Prashaad M, Siew Rachel Wan En, Aw Amelia Yun Yi, Hui Yi Tan Janice, Gulam Mohamed Muhammad Yaaseen, Siew Noi Janis Tye, Prasad Kalpana, Tan Kevin, Kuhle Jens, Chao Yinxia, Ho Ivy Ai-Wei, Yeo Tianrong
Duke-NUS Medical School, Singapore, Singapore.
Department of Neurology (Tan Tock Seng Hospital Campus), National Neuroscience Institute, Singapore, Singapore.
Ther Adv Infect Dis. 2025 Sep 9;12:20499361251370471. doi: 10.1177/20499361251370471. eCollection 2025 Jan-Dec.
Immunosuppressive treatment can attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses. Moreover, SARS-CoV-2 has neuroinvasive potential and may induce a persistent pro-inflammatory milieu following infection.
To investigate if diminished post-vaccine humoral responses can be overcome with additional vaccine doses and/or breakthrough COVID-19 infections, and if COVID-19 infection can lead to a pro-inflammatory state with neuroaxonal/neuroglial injury in the intermediate-term in patients with central nervous system (CNS) neuroimmunological diseases.
A prospective observational study conducted at National Neuroscience Institute, Singapore.
Serum levels of SARS-CoV-2 neutralising antibodies (NAbs) were measured in patients with CNS neuroimmunological diseases following their fourth SARS-CoV-2 mRNA vaccine (V4), or after breakthrough COVID-19 infection following three prior SARS-CoV-2 mRNA vaccinations, or both. Serum levels of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF) were evaluated post-COVID-19 infection and post-V4, compared to baseline within individuals. Serum neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of neuroaxonal and astroglial injury, respectively, were measured at baseline and post-COVID-19 infection within patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD).
Sixty-one patients with various CNS neuroimmunological diseases were recruited, including 34 with MS and 19 with NMOSD. All had received at least three doses of the SARS-CoV-2 mRNA vaccine. Patients on anti-CD20/sphingosine-1-phosphate-receptor modulators (S1PRM) showed significantly reduced NAbs levels in both post-V4 and post-COVID-19 infection scenarios, compared to patients on other immunotherapies. No significant differences between baseline and post-COVID-19 infection concentrations of IL-6 and TNF were observed. Within RRMS and NMOSD patients, NfL and GFAP levels remained similar between baseline and post-COVID-19 infection.
Anti-CD20/S1PRM treatments are associated with persistently diminished humoral responses post-V4/infection. Patients with CNS neuroimmunological diseases do not show biomarker evidence of intermediate-term pro-inflammatory states and neural injury after COVID-19 infection.
免疫抑制治疗可减弱严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗诱导的免疫反应。此外，SARS-CoV-2具有神经侵袭潜力，感染后可能诱导持续的促炎环境。
研究额外的疫苗剂量和/或突破性新冠病毒感染是否能克服疫苗接种后体液反应减弱的情况，以及新冠病毒感染在中枢神经系统（CNS）神经免疫疾病患者中期是否会导致伴有神经轴突/神经胶质损伤的促炎状态。
在新加坡国立神经科学研究所进行的一项前瞻性观察研究。
在患有中枢神经系统神经免疫疾病的患者中，于其接种第四剂SARS-CoV-2 mRNA疫苗（V4）后、或在先前接种三剂SARS-CoV-2 mRNA疫苗后发生突破性新冠病毒感染后、或两者兼有的情况下，测量SARS-CoV-2中和抗体（NAbs）的血清水平。与个体内的基线水平相比，在新冠病毒感染后和V4后评估促炎细胞因子白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）的血清水平。在复发缓解型多发性硬化症（RRMS）和视神经脊髓炎谱系障碍（NMOSD）患者中，分别在基线和新冠病毒感染后测量血清神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP），它们分别是神经轴突和星形胶质细胞损伤的生物标志物。
招募了61例患有各种中枢神经系统神经免疫疾病的患者，包括34例多发性硬化症患者和19例视神经脊髓炎谱系障碍患者。所有患者均接受了至少三剂SARS-CoV-2 mRNA疫苗。与接受其他免疫疗法的患者相比，接受抗CD20/鞘氨醇-1-磷酸受体调节剂（S1PRM）治疗的患者在V4后和新冠病毒感染后的NAbs水平均显著降低。未观察到IL-6和TNF在基线和新冠病毒感染后的浓度有显著差异。在RRMS和NMOSD患者中，NfL和GFAP水平在基线和新冠病毒感染后保持相似。
抗CD20/S1PRM治疗与V4后/感染后持续减弱的体液反应相关。中枢神经系统神经免疫疾病患者在新冠病毒感染后未显示中期促炎状态和神经损伤的生物标志物证据。
