Real-world impact of the COVID-19 pandemic in people with multiple sclerosis

项目总结和摘要。 由SARS-CoV-2感染引起的COVID-19大流行给约300万人带来了新的挑战 多发性硬化症（PwMS）的发病率。主要的知识差距包括常见MS 疾病修饰疗法（DMT）调节COVID-19的风险和严重程度，COVID-19的疗效 考虑到从COVID-19疫苗中排除PwMS， 试验，以及大流行对PwMS中社会联系和健康结果的更广泛后果。 这些差距产生了快速生成严格信息的迫切需求，以指导临床 管理为了应对这些挑战，我们创建了MSReCOV（MS Resilience to COVID-19） 2020年3月下旬通过组建MS中心网络进行合作，以利用现有的临床研究 基础设施和收集患者报告的数据。鉴于PwMS和医疗保健之间的相互作用减少 系统和限制在人的研究活动在开始和在随后的阶段，我们 在大流行期间，迅速部署在线调查研究，直接从PwMS收集实时数据， 补充医生报告的登记工作。为了补充MSReCOV，我们将询问 Optum数据仓库，包含来自约40，000个虚拟队列的综合索赔和电子健康记录数据 商业保险PwMS（每年）。基于MSReCOV和Optum基础设施，我们提出 以下内容旨在弥补知识差距。目的1：检查MS DMT与 2019冠状病毒病。我们将检验某些DMT（如IFNb）与COVID减少相关的假设。 19风险，而其他如B细胞耗竭剂与COVID-19风险增加有关。目标二： 检查COVID-19疫苗在MS中的有效性和安全性以及与MS结局的关联。我们将 首先检验COVID-19疫苗在PwMS中有效和安全并且在临床上不会恶化的假设 相关患者报告的神经功能结局（PRO），其次检验假设B- 细胞消耗治疗降低疫苗效力，而其它DMT则不会。目标3：检查 PwMS中个人社交网络和MS结果的流行。基于我们之前的工作，我们将 检验大流行（与SARS-CoV-2感染无关）对 PwMS的神经功能通过改变个人社会联系。鉴于COVID-19的严重程度 大流行，从拟议的研究中出现的真实世界证据将为临床管理提供重要信息 PwMS在快速变化的神经系统护理景观。该项目与 NIH/NINDS的使命是减少MS等神经系统疾病的负担， 流行病

PROJECT SUMMARY AND ABSTRACT. The COVID-19 pandemic due to the SARS-CoV-2 infection poses new challenges to the ~3 million persons with multiple sclerosis (PwMS) worldwide. Major knowledge gaps include the extent to which common MS disease modifying therapies (DMTs) modulate the COVID-19 risk and severity, the efficacy of the COVID-19 vaccines and any impact on MS neurological outcomes given the exclusion of PwMS from COVID-19 vaccine trials, and the broader consequence of the pandemic on social connection and health outcomes in PwMS. These gaps create a critical need to rapidly generate rigorous information with which to guide clinical management. To address these challenges, we created the MSReCOV (MS Resilience to COVID-19) Collaborative in late March 2020 by assembling a network of MS Centers to leverage existing clinical research infrastructure and collect patient-reported data. Given the reduced interaction between PwMS and healthcare systems and the restriction on in-person research activities at the onset and during subsequent phases, we rapidly deployed online survey studies to gather real-time data directly from PwMS during the pandemic to complement the effort of physician-reported registries. To complement MSReCOV, we will interrogate the Optum data warehouse of integrated claims and electronic health records data from a virtual cohort of ~40,000 commercially insured PwMS (per year). Building on the MSReCOV and Optum infrastructure, we propose the following aims to address the knowledge gaps. Aim 1: Examine the association between MS DMTs and COVID-19. We will test the hypothesis that certain DMTs such as IFNb are associated with reduced COVID- 19 risk, while others such as B-cell depleting agents are associated with increased COVID-19 risk. Aim 2: Examine the COVID-19 vaccine efficacy and safety in MS and association with MS outcomes. We will first test the hypothesis that COVID-19 vaccines are effective and safe in PwMS and do not worsen clinically relevant patient-reported outcomes (PROs) of neurological function, and secondarily test the hypothesis that B- cell depleting treatments reduce vaccine efficacy whereas other DMTs do not. Aim 3: Examine the effect of the pandemic on personal social network and MS outcomes in PwMS. Building on our prior works, we will test the hypothesis that the pandemic (independent of the SARS-CoV-2 infection) negatively influences the neurological function in PwMS by altering personal social connection. Given the extent of the COVID-19 pandemic, real-world evidence emerging from the proposed study will critically inform the clinical management of PwMS during the rapidly changing landscape of neurological care. The project is highly relevant to the mission of the NIH/NINDS to reduce the burden of neurological diseases such as MS in the setting of the pandemic.