Department of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Alzahra Research Institute, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Isfahan, Iran.
Mult Scler Relat Disord. 2022 Jan;57:103417. doi: 10.1016/j.msard.2021.103417. Epub 2021 Nov 22.
Various studies indicated blunted humoral responses to COVID-19 mRNA and viral vector vaccines among people with multiple sclerosis (pwMS) on sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20); however, limited evidence was found regarding SARS-CoV-2 serology after inactivated virus vaccination.
To provide evidence regarding humoral response to COVID-19 inactivated virus vaccination among pwMS on disease-modifying therapies (DMTs).
A cohort study was carried out in Isfahan, Iran, enrolling DMT-exposed pwMS and unexposed (UX) healthy participants. Post-vaccination anti-SARS-CoV-2 Spike IgG serology testing was carried out among the participants and compared between participants based on their DMT exposure, using proper statistical tests. A multivariable logistic regression model was used to control for confounding. Association between the second vaccine dose-to-phlebotomy (vac2phleb) and the humoral response was investigated in each DMT-exposed cohort, using linear regression. Among the aCD20 cohort, the association of the last aCD20 infusion-to-first vaccine dose period with serostatus was investigated using an unpaired t-test.
After enrolling 358 participants (144 pwMS and 214 healthy), blunted humoral responses were only observed in fingolimod (Log mean diff. [SE]: 0.72 [0.18], P = 0.001) and aCD20 (Log mean diff. [SE]: 0.75 [0.15], P < 0.001) cohorts compared to the UX cohort. Multivariable analysis confirmed the results. The study did not achieve enough statistical power to detect a significant association between the vac2phleb period and humoral responses. The last aCD20 infusion to first vaccination dose period was longer in the seroconverted pwMS on aCD20 (mean diff. [SE]: 8.43 weeks [2.57], P = 0.005).
The results of this study mirrored the results of previous studies among mRNA- or viral vector-vaccinated pwMS on DMTs. Therefore, it can be concluded that mode of action contributes less than timing, to the efficiency of vaccination strategies among pwMS on DMTs - especially the ones on S1PR modulators and aCD20. Meanwhile, the mentioned pwMS should be advised to receive early boosters and remain vigilant until further data becomes available and more efficient vaccination strategies are crafted.
多项研究表明,在接受鞘氨醇 1-磷酸受体(S1PR)调节剂和抗 CD20 治疗(aCD20)的多发性硬化症(pwMS)患者中,COVID-19 mRNA 和病毒载体疫苗的体液免疫反应减弱;然而,关于灭活病毒疫苗接种后 SARS-CoV-2 血清学的证据有限。
为接受疾病修正治疗(DMT)的 pwMS 提供关于 COVID-19 灭活病毒疫苗接种后体液免疫反应的证据。
在伊朗伊斯法罕进行了一项队列研究,纳入了接受 DMT 暴露的 pwMS 和未暴露(UX)的健康参与者。对参与者进行了接种后抗 SARS-CoV-2 刺突 IgG 血清学检测,并根据他们的 DMT 暴露情况,使用适当的统计检验对参与者进行了比较。使用多变量逻辑回归模型控制混杂因素。在每个接受 DMT 暴露的队列中,使用线性回归研究了第二剂疫苗接种至采血(vac2phleb)与体液反应之间的关系。在 aCD20 队列中,使用配对 t 检验研究了最后一次 aCD20 输注至第一次疫苗接种剂量期间与血清状态之间的关系。
在纳入 358 名参与者(144 名 pwMS 和 214 名健康参与者)后,与 UX 队列相比,仅在芬戈利莫德(Log 平均差异 [SE]:0.72 [0.18],P = 0.001)和 aCD20 (Log 平均差异 [SE]:0.75 [0.15],P <0.001)队列中观察到体液免疫反应减弱。多变量分析证实了这些结果。该研究没有足够的统计能力来检测 vac2phleb 期与体液反应之间的显著关联。在接受 aCD20 治疗的血清转化 pwMS 中,最后一次 aCD20 输注至第一次接种疫苗的时间间隔较长(平均差异 [SE]:8.43 周 [2.57],P = 0.005)。
本研究的结果与先前在接受 DMT 的 mRNA 或病毒载体疫苗接种的 pwMS 中进行的研究结果一致。因此,可以得出结论,作用模式对 DMT 治疗的 pwMS 接种策略的效率的影响小于时间,尤其是对 S1PR 调节剂和 aCD20 的影响。同时,应该建议上述 pwMS 尽早接受加强针,并保持警惕,直到获得更多数据并制定出更有效的接种策略。