文献检索，用中文搜 PubMed

Abstract

BACKGROUND

COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs.

METHODS

This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups.

RESULTS

A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI).

CONCLUSION

mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

摘要

背景

新冠病毒疫苗推荐多发性硬化症（pwMS）患者使用。接种疫苗后，除接受 B 细胞耗竭治疗和非选择性 S1P 调节剂治疗的 pwMS 外，接受疾病修正治疗（DMT）的 pwMS 体内均可产生足够的体液免疫应答。然而，大多数关于新冠病毒疫苗免疫的报告研究都包含了 mRNA 疫苗，关于灭活病毒疫苗的反应、长期保护作用以及与 mRNA 疫苗的比较研究非常有限。在这里，我们旨在通过一项大型全国性接受 DMT 的 pwMS 队列的研究，调查 mRNA 和灭活病毒疫苗接种后体液疫苗反应与新冠病毒感染结局之间的关系。

方法

这是一项关于接受 DMT 的新冠病毒疫苗接种 pwMS 的横断面和前瞻性多中心研究。在接种两剂灭活病毒（科兴）或 mRNA（辉瑞-生物科技）疫苗后，采集 pwMS 有或无 DMT 治疗者和健康对照者的血样。根据 pwMS 接受的 DMT 作用模式对 pwMS 进行分组。采用化学发光微粒子免疫分析法评估 SARS-CoV-2 IgG 滴度。对该研究队列的一个代表性样本进行了为期一年的随访。比较了 mRNA 和灭活病毒组以及 pwMS 亚组之间的新冠病毒感染状态和临床结局。

结果

共纳入 1484 名 pwMS（1387 名治疗，97 名未治疗）和 185 名健康对照者（男性/女性：544/1125）。其中 852 名（51.05%）接受了辉瑞-生物科技疫苗，817 名（48.95%）接受了科兴疫苗。mRNA 和灭活病毒疫苗均产生相似的血清阳性率；然而，与科兴疫苗组（823±1.774）相比，辉瑞-生物科技疫苗组的抗体滴度显著更高（7.175±10.074）（p<0.001）。接受奥瑞珠单抗、芬戈莫德和克拉屈滨治疗的 pwMS 与两种疫苗类型的健康对照者相比，体液反应较低。在平均 327±16 天后，联系到的 704 名 pwMS 中有 246 名（34.9%）发生了新冠病毒感染，其中 83%为无症状或轻症。接受 BioNTech 或 Sinovac 疫苗接种的参与者之间的新冠病毒感染率没有显著差异。此外，回归分析显示，除体重指数（BMI）外，年龄、性别、扩展残疾状态量表评分（EDSS）、疫苗接种次数、DMT 类型或体液抗体反应与新冠病毒感染率和疾病严重程度之间没有关联。