NeuroCovid Autoantibodies: Establishing a research pipeline

项目摘要 新冠肺炎与越来越多的外周和中枢神经系统并发症有关。 很明显，这些症状的一部分，包括急性坏死性脑病，类固醇- 反应性脑炎和格林-巴利综合征可能是由于SARS-CoV-2引发的自身免疫 感染。迫切需要前瞻性地研究急性和慢性神经并发症。 新冠肺炎，并确定哪些综合征是起源于神经炎性的-特别是那些由副- 传染性自身免疫。虽然针对SARS-CoV-2的抗病毒疗法仍在开发中，但自身免疫 中枢神经系统疾病对免疫抑制非常敏感。因此，识别生物标记物的子集 具有自身免疫性中枢神经系统综合征的新冠肺炎患者可立即影响临床治疗。 在过去的7年里，加州大学旧金山分校一个由神经学家和基础科学家组成的独特的跨学科团队 成立的目的是开发和部署一种集成的方法来快速对抗与以下疾病相关的神经抗体 脑炎，明确的意图是发现和验证临床上可操作的生物标记物 揭示这些证候背后的基本发病机制。这个 这些努力的核心是一个正在进行的患者队列，称为NID(神经炎症性疾病)队列， 由疑似感染性或炎症性脑炎的患者组成。这个群体现在是1,500人。 加州大学旧金山分校和世界各地其他中心的临床医生转介的患者。这群人已经有了 刺激了有史以来第一个经过临床验证的脑脊液下一代元基因组的开发 测序鉴定一种新的副肿瘤性自身免疫综合征 精原细胞瘤对男性的意义及儿童急性精原细胞瘤肠道病毒脑脊液抗体的鉴定 松弛的脊髓炎。在这里，我们建议调整现有的临床研究和实验室基础设施，以 招募并调查新冠肺炎患者是否患有持续神经病学 后遗症有中枢神经系统炎症。我们将与美国国立卫生研究院的同事合作开展这项工作， 耶鲁大学以及加州大学旧金山分校医学中心、扎克伯格旧金山综合医院和 加州大学伯尼奥夫分校儿童医院。我们寻求紧急资金，以加快我们识别反恐怖主义的工作 神经系统综合征患者中与SARS-CoV-2感染相关的神经性自身抗体1例 立即瞄准。 目的1：鉴定新冠肺炎神经综合征患者脑脊液中的自身抗体。

PROJECT ABSTRACT COVID-19 is associated with a growing number of peripheral and central nervous system complications. It has become clear that a subset of these syndromes, including acute necrotizing encephalopathy, steroid- responsive encephalitis and Guillain-Barré syndrome, are likely due autoimmunity triggered by SARS-CoV-2 infection. There is an urgent need to prospectively investigate the acute and chronic neurologic complications of COVID-19 and determine which syndromes are neuroinflammatory in origin — particularly those caused by para- infectious autoimmunity. While anti-viral therapeutics are still being developed for SARS-CoV-2, autoimmune CNS conditions can be very responsive to immunosuppression. Thus, identifying biomarkers for a subset of COVID-19 patients with autoimmune CNS syndromes could immediately impact clinical management. Over the past 7 years, a unique interdisciplinary team of neurologists and basic scientists at UCSF was formed to develop and deploy an integrated approach to rapidly anti-neural antibodies associated with encephalitis, with the explicit intent to discover and validate clinically actionable biomarkers in addition to uncovering the fundamental mechanisms of disease pathogenesis underlying these syndromes. The centerpiece of these efforts is an ongoing patient cohort called the NID (Neuroinflammatory Disease) cohort, consisting of patients with suspected infectious or inflammatory encephalitis. This cohort is now >1,500 patients referred by clinicians at UCSF and from other centers around the world. Already, this cohort has spurred the development of the first ever clinically validated cerebrospinal fluid metagenomic next-generation sequencing assay, the identification of a novel paraneoplastic autoimmune syndrome with important implications for men with seminoma and the identification of enteroviral CSF antibodies in children with acute flaccid myelitis. Here, we propose to adapt this existing clinical research and laboratory infrastructure to enroll and investigate the urgent question whether COVID-19 patients with ongoing neurologic sequelae have CNS inflammation. We will perform this work in collaboration with colleagues at the NIH, Yale University as well as at UCSF Medical Center, Zuckerberg San Francisco General Hospital and UCSF Benioff Children's Hospital. We seek emergency funding to accelerate our work on identifying anti- neural autoantibodies associated with SARS-CoV-2 infection in patients with neurologic syndromes in 1 immediate aim. Aim 1: Identify autoantibodies in the CSF of COVID-19 patients with neurologic syndromes.