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抗 CD20 治疗患者接种 COVID-19 疫苗后产生的强大 T 细胞反应:一项前瞻性队列研究。

Robust T-Cell Responses in Anti-CD20-Treated Patients Following COVID-19 Vaccination: A Prospective Cohort Study.

机构信息

Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

Department of Medicine, Division of Rheumatology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.

出版信息

Clin Infect Dis. 2022 Aug 24;75(1):e1037-e1045. doi: 10.1093/cid/ciab954.

Abstract

BACKGROUND

Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population.

METHODS

This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22).

RESULTS

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination.

CONCLUSIONS

Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.

摘要

背景

接受抗 CD20 治疗的患者尤其有发生严重 2019 冠状病毒病(COVID-19)的风险;然而,对于该人群中 COVID-19 疫苗的有效性知之甚少。

方法

这项前瞻性观察性队列研究评估了接受利妥昔单抗治疗风湿性疾病或奥瑞珠单抗治疗多发性硬化症的患者(n = 37)与免疫功能正常的个体(n = 22)接种 2 剂基于 mRNA 的 COVID-19 疫苗后,体液和 T 细胞反应。

结果

仅 69.4%的患者可检测到严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)特异性抗体,且水平明显低于所有发生血清转化的对照组。与抗体不同,Spike(S)特异性 CD4 T 细胞在免疫功能正常和抗 CD20 治疗的患者中同样被检测到(85-90%),并且主要是 Th1 表型。与对照组(66.7%)相比,奥瑞珠单抗(96.2%)和利妥昔单抗治疗的患者(81.8%)的 S 特异性 CD8 T 细胞的反应率更高。S 特异性 CD4 和 CD8 T 细胞具有多功能性,但与对照组相比,患者中表达的效应分子更多。在随访期间,3 名多发性硬化症患者无 SARS-CoV-2 特异性抗体应答,发生轻度突破性感染。其中 1 名患者接种后未检测到 S 特异性 T 细胞。

结论

我们的研究表明,尽管存在体液反应受损,接受抗 CD20 治疗的患者仍能够对 mRNA COVID-19 疫苗产生强烈的 T 细胞反应。这可能在减少严重 COVID-19 并发症方面发挥重要作用。

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