Department of Neurology, National Neuroscience Institute (Tan Tock Seng Campus), Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore.
Division of Neurology, Department of Medicine, National University Hospital, Singapore, Singapore.
Mult Scler Relat Disord. 2022 Sep;65:104003. doi: 10.1016/j.msard.2022.104003. Epub 2022 Jun 26.
In pre-vaccinated people with multiple sclerosis (MS), certain disease-modifying therapies (DMTs), particularly the anti-CD20 treatments, appear to be associated with an increased risk of COVID-19 infection and indeed with severe infection. It is still not known if such observations extend to vaccinated individuals and there have been considerably fewer studies in aquaporin-4-antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) patients. In this study, we investigated the rates of symptomatic COVID-19 infection in adult patients with MS, AQP4-NMOSD and MOGAD who had received 2 doses of SARS-CoV-2 mRNA vaccine.
This was a prospective observational study conducted at the 2 main neuroimmunology referral centres in Singapore. Only patients on active follow-up were recruited to ensure robust data collection. Data on demographics, disease history, DMTs and SARS-CoV-2 mRNA vaccinations were recorded, and for those infected with COVID-19, data on COVID-19 infection was collected.
Nineteen (13 MS, 5 AQP4-NMOSD, 1 MOGAD) out of 365 (231 MS, 106 AQP4-NMOSD, 28 MOGAD) patients had COVID-19 infection despite 2 doses of SARS-CoV-2 mRNA vaccine. Amongst the infected patients, 11 patients were on DMTs (3 rituximab, 2 interferons, 1 azathioprine, 1 mycophenolate, 1 prednisolone, 1 cladribine, 1 alemtuzumab, 1 fingolimod), while 8 patients were untreated. The crude infection rate was calculated using time-at-risk analysis, revealing that rituximab had the highest infection rate amongst all the DMTs. A lower crude infection rate was observed in patients who received a third vaccination. The majority of infections were mild and no patients required oxygen supplementation.
Our findings suggest that patients on rituximab are still at risk of COVID-19 infection after 2 vaccinations and the receipt of a third vaccination may help to prevent infection. Future large scale studies will be required to better delineate the infection risk of different DMTs after the second and subsequent vaccinations.
在未接种疫苗的多发性硬化症 (MS) 患者中,某些疾病修正疗法 (DMT),特别是抗 CD20 治疗,似乎与 COVID-19 感染风险增加有关,甚至与严重感染有关。目前尚不清楚这些观察结果是否适用于接种疫苗的个体,并且在水通道蛋白 4 抗体视神经脊髓炎谱系障碍 (AQP4-NMOSD) 和髓鞘少突胶质细胞糖蛋白抗体相关疾病 (MOGAD) 患者中进行的研究要少得多。在这项研究中,我们调查了接受过 2 剂 SARS-CoV-2 mRNA 疫苗的 MS、AQP4-NMOSD 和 MOGAD 成年患者中出现症状性 COVID-19 感染的发生率。
这是在新加坡的 2 个主要神经免疫学转诊中心进行的前瞻性观察性研究。仅招募正在接受积极随访的患者,以确保可靠的数据收集。记录了人口统计学、疾病史、DMT 和 SARS-CoV-2 mRNA 疫苗接种的数据,对于感染 COVID-19 的患者,还收集了 COVID-19 感染的数据。
在 365 名患者(231 名 MS、106 名 AQP4-NMOSD、28 名 MOGAD)中,有 19 名(13 名 MS、5 名 AQP4-NMOSD、1 名 MOGAD)患者尽管接受了 2 剂 SARS-CoV-2 mRNA 疫苗,但仍感染了 COVID-19。在感染的患者中,有 11 名患者正在接受 DMT(3 名利妥昔单抗、2 名干扰素、1 名硫唑嘌呤、1 名霉酚酸酯、1 名泼尼松龙、1 名克拉屈滨、1 名阿仑单抗、1 名芬戈莫德),而 8 名患者未接受治疗。使用风险时间分析计算了感染率,结果表明,利妥昔单抗是所有 DMT 中感染率最高的药物。接受第三次疫苗接种的患者感染率较低。大多数感染为轻度,无需吸氧。
我们的研究结果表明,接受利妥昔单抗治疗的患者在接种 2 剂疫苗后仍有感染 COVID-19 的风险,而接种第 3 剂疫苗可能有助于预防感染。未来需要进行大规模研究,以更好地区分第 2 剂和第 2 剂后不同 DMT 的感染风险。