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

项目摘要和摘要。 由SARS-CoV-2感染引起的新冠肺炎大流行对约300万人提出了新的挑战 世界各地的多发性硬化症(PWMS)。主要知识差距包括普通多发性硬化症的程度 疾病修饰疗法(DMT)调节新冠肺炎的风险和严重程度，以及新冠肺炎的疗效 鉴于新冠肺炎疫苗中排除了PWMS，疫苗及其对MS神经预后的任何影响 试验，以及大流行对PWMS的社会联系和健康结果的更广泛的后果。 这些差距产生了快速生成用于指导临床的严格信息的迫切需要 管理层。为了应对这些挑战，我们创建了MSReCOV(MS对新冠肺炎的弹性) 在2020年3月下旬通过组建MS中心网络来利用现有临床研究进行协作 基础设施和收集患者报告的数据。鉴于PWMS和医疗保健之间的互动减少 系统和对面对面研究活动的限制，在开始和随后的阶段，我们 快速部署在线调查研究，在疫情期间直接从PWMS收集实时数据，以 补充医生报告注册的努力。为了补充MSReCOV，我们将询问 来自约40,000个虚拟队列的集成索赔和电子健康记录数据的Optus数据仓库 商业保险的PWMS(每年)。在MSReCOV和Optus基础设施的基础上，我们建议 以下内容旨在解决知识差距问题。目标1：检查MS DMT和 新冠肺炎。我们将测试这样的假设，即某些DMT，如IFNb，与COVID减少有关- 19风险，而其他如B细胞耗尽剂与新冠肺炎风险增加有关。目标2： 检查新冠肺炎疫苗在多发性硬化症中的有效性和安全性，以及与多发性硬化症预后的关系。我们会 首先检验新冠肺炎疫苗在PWMS中有效、安全且不会在临床上恶化的假设 相关患者报告的神经功能结果(PRO)，并二次检验B-B- 细胞耗尽疗法会降低疫苗的效力，而其他DMT并非如此。目标3：检查以下项目的效果 个人社交网络上的流行病和多发性硬化症在PWMS中的结果。在我们以前工作的基础上，我们将 检验大流行(独立于SARS-CoV-2感染)对 通过改变个人社交关系改善PWMS的神经功能。鉴于新冠肺炎的范围 大流行，拟议研究中出现的真实世界证据将为临床管理提供关键信息 在迅速变化的神经护理格局中的PWMS。该项目与 NIH/NINDS的使命是减轻多发性硬化症等神经疾病在 大流行。

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.