Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
Ann Neurol. 2022 Jun;91(6):782-795. doi: 10.1002/ana.26346. Epub 2022 Apr 1.
The objective of this study was to determine the impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.
Patients with MS aged 18 to 60 years were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity.
Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non-White). Most common DMTs were ocrelizumab (OCR)-40%; natalizumab -17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. One hundred seventy-seven patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non-OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID-19) clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized.
DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782-795.
本研究旨在确定多发性硬化症（MS）疾病修正疗法（DMT）对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的细胞和体液免疫产生的影响。
评估了年龄在 18 至 60 岁之间的 MS 患者的抗核衣壳和抗 Spike 受体结合域（RBD）抗体，采用电化学发光免疫测定法；使用基于多表位珠的免疫分析（MBI）对 Spike 蛋白、RBD、N 端结构域进行抗体反应检测；采用活病毒免疫荧光微中和测定法；采用 TruCulture 酶联免疫吸附测定法（ELISA）对 SARS-CoV-2 Spike 进行 T 细胞反应检测；采用 IL-2 和 IFNγ ELISA 斑点测定法。通过 DMT 类别比较检测结果。采用 Spearman 相关分析和多变量分析来检查免疫反应与感染严重程度之间的关联。
2021 年 1 月 6 日至 2021 年 7 月 21 日期间，共招募了 389 名 MS 患者（平均年龄 40.3 岁；74%为女性；62%为非白人）。最常见的 DMT 为奥瑞珠单抗（OCR）-40%；那他珠单抗-17%，鞘氨醇 1-磷酸受体（S1P）调节剂-12%；未治疗的占 15%。177 名患者（46%）有 SARS-CoV-2 感染的实验室证据；130 名有症状感染，47 名无症状感染。与其他组相比，OCR 的抗体反应明显减弱（p≤0.0001）。S1P 组的 T 细胞反应（IFNγ）降低（p=0.03），那他珠单抗组升高（p<0.001），其他 DMT 组（包括 OCR）相似。在 OCR（r=0.45，p=0.0002）和非-OCR（r=0.64，p<0.0001）中，细胞和体液反应均呈中度相关。免疫反应不因种族/民族而异。COVID-19 临床病程在大多数情况下不严重，且在 DMT 之间相似；130 例中有 7%（9/130）住院。
DMT 对 SARS-CoV-2 感染的体液和细胞免疫反应有不同的影响。在这个相对年轻且无残疾的 MS 患者群体中，免疫反应与 COVID-19 临床严重程度无相关性。
