Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
Mult Scler Relat Disord. 2024 Sep;89:105770. doi: 10.1016/j.msard.2024.105770. Epub 2024 Jul 15.
Patients with multiple sclerosis (MS) treated with anti-CD20 therapies such as rituximab may have increased risk of severe COVID-19 disease. Vaccination induces protective immunity, but humoral vaccine response is known to be attenuated in rituximab-treated MS-patients-patients, which has indicated a need for real world data on severe morbidity and mortality from COVID-19 after vaccination.
Rituximab-treated patients treated at Haukeland University Hospital were identified through the National MS Registry and invited to participate in the study by giving a consent and providing a blood sample 3 weeks or later after ordinary COVID-19- vaccination, i.e. 2 doses given with a standard interval of 3 weeks. Blood samples were analysed with Enzyme-Linked Immunosorbent assay (ELISA) to evaluate humoral vaccine response with screening test against receptor-binding domain (RBD) and confirmatory Spike IgG-specific ELISA. A haemagglutination test (HAT) was performed as a marker of neutralizing antibodies. Patient serum concentration of rituximab were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Registry data from the Norwegian MS registry and information on hospitalization from patient records were collected and linked to laboratory results.
111 patients were included in the study. A total of 7 (6.3%) were hospitalized due to COVID-19 disease during the observation period. No patient was admitted to ICU and there were no deaths. 34.2% did not have detectable titre of SARS CoV-2 Spike IgG antibodies, 72.1% did not have a detectable titre of SARS CoV-2 RBD antibodies, and 88.2% did not have a detectable HAT titre. There was a correlation between hospitalisation and the absence of SARS CoV-2 Spike IgG antibody titre, and between hospitalisation and MS disease duration, as well as between spike IgG antibody titre and CD19 B-cell count, time since last rituximab infusion, cumulative rituximab treatment time and total IgG level in the patients.
A substantial proportion of rituximab-treated MS-patients-patients did not have detectable humoral vaccine responses after 2 doses of COVID-19 vaccination. Despite this, the cumulative percentage of patients hospitalized with COVID-19 disease throughout the observation period of 22 months was low, and no patients required ICU treatment. The results support that vaccinated MS-patients treated with rituximab have a protective effect against serious Covid-19 infection.
接受抗 CD20 治疗（如利妥昔单抗）的多发性硬化症（MS）患者可能有罹患严重 COVID-19 疾病的风险增加。疫苗接种可诱导保护性免疫，但已知利妥昔单抗治疗的 MS 患者的体液疫苗反应减弱，这表明需要关于 COVID-19 疫苗接种后严重发病率和死亡率的真实世界数据。
通过国家 MS 登记册确定在豪克兰大学医院接受利妥昔单抗治疗的患者，并通过同意书和在普通 COVID-19 疫苗接种后 3 周或更长时间（即给予标准间隔 3 周的 2 剂）提供血样来邀请他们参加研究。使用酶联免疫吸附试验（ELISA）分析血样，以评估针对受体结合域（RBD）的体液疫苗反应，并通过 Spike IgG 特异性 ELISA 进行确认。进行血凝试验（HAT）作为中和抗体的标志物。使用液相色谱串联质谱法（LC-MS/MS）定量患者血清中的利妥昔单抗浓度。从挪威 MS 登记册收集登记数据和患者记录中的住院信息，并将其与实验室结果相关联。
共有 111 名患者纳入研究。在观察期间，共有 7 名（6.3%）因 COVID-19 疾病住院。没有患者入住 ICU，也没有死亡。34.2%的患者没有检测到 SARS CoV-2 Spike IgG 抗体的滴度，72.1%的患者没有检测到 SARS CoV-2 RBD 抗体的滴度，88.2%的患者没有检测到 HAT 滴度。住院与 SARS CoV-2 Spike IgG 抗体滴度的缺失、住院与 MS 疾病持续时间、Spike IgG 抗体滴度与 CD19 B 细胞计数、末次利妥昔单抗输注后时间、累积利妥昔单抗治疗时间以及患者总 IgG 水平之间存在相关性。
接受利妥昔单抗治疗的 MS 患者在接种 2 剂 COVID-19 疫苗后，有相当比例的患者未检测到体液疫苗反应。尽管如此，在 22 个月的观察期间，因 COVID-19 疾病住院的患者累计百分比仍然较低，没有患者需要 ICU 治疗。结果支持接受利妥昔单抗治疗的接种疫苗的 MS 患者对严重 COVID-19 感染具有保护作用。
