Understanding the long term impact of COVID-19 on the brain through advanced MR imaging and spectroscopy

项目摘要/摘要 自世界卫生组织于2020年3月宣布新冠肺炎为大流行以来，越来越多的人 有证据表明，这种疾病影响到多个器官，包括中枢神经系统(CNS)。这个 COVID大脑高级成像网络(COVID-Brain)的成立是为了阐明长期中枢神经系统 新冠肺炎的病理生理学研究具有系统性和前瞻性。我们使用高度敏感、和谐、 3特斯拉先进的磁共振技术用于询问神经炎、神经变性和脑血管 SARS-CoV-2感染后持续神经后遗症患者的疾病。五个网站 也是其他多站点神经成像计划的合作伙伴(明尼苏达大学、梅奥诊所罗切斯特、 哈佛大学/马萨诸塞州综合医院，约翰霍普金斯大学，休斯顿卫理公会研究 研究所)收集纵向多模式MRI(T1、FLAIR、弥散磁共振、磁化率加权MRI、单 和多体素磁共振波谱和伪连续动脉自旋标记)、临床、神经认知和 实验室确诊的有神经系统症状的冠状病毒感染后患者的炎性血液生物标志物数据 和配对的对照组。 新冠肺炎相关中枢神经系统损伤的病理生理成分可能导致 2022年ADRD中强调的阿尔茨海默病及其相关痴呆(AD/ADRD)风险增加 峰会建议。因此，在目标1中，我们将评估长期冠状病毒感染患者的AD/ADRD风险 使用基于血液的生物标记物(Abeta1-40、Abeta1-42、pTau181、NFL和GFAP)，并确定 ApoEε4状态、年龄、性别、种族、种族和健康的社会决定因素会改变这种风险。在目标2中，我们将 研究这些基于血液的生物标记物与神经炎症的MRI/MRS标记物的关系， 慢性冠状病毒感染患者神经退行性变与脑血管疾病及载脂蛋白ε4状态 年龄、性别、种族、种族和健康的社会决定因素改变了这些联系。 这项研究提供的见解将对开发针对疾病的修改疗法至关重要 与COVID-19的长期中枢神经系统后果相关的潜在病理机制， 包括增加AD/ADRD的风险。

PROJECT SUMMARY/ABSTRACT Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing evidence has shown that the disease affects multiple organs, including the central nervous system (CNS). The COVID BRain Advanced Imaging Network (COVID-BRAIN) was formed to elucidate the long-term CNS pathophysiology of COVID-19 systematically and prospectively. We use highly sensitive, harmonized, advanced MR technology at 3 tesla to interrogate neuroinflammation, neurodegeneration and cerebrovascular disease in individuals with persistent neurological sequalae following SARS-CoV-2 infection. Five sites that also partner in other multi-site neuroimaging initiatives (University of Minnesota, Mayo Clinic Rochester, Harvard University/Massachusetts General Hospital, Johns Hopkins University, Houston Methodist Research Institute) collect longitudinal multi-modal MRI (T1, FLAIR, diffusion MRI, susceptibility-weighted MRI, single- and multi-voxel MR spectroscopy and pseudo-continuous arterial spin labeling), clinical, neurocognitive and inflammatory blood biomarker data from laboratory confirmed post-COVID cases with neurological symptoms and matched controls. The pathophysiologic components of CNS injury associated with COVID-19 can potentially lead to increased risk for Alzheimer’s disease and its related dementias (AD/ADRD) as emphasized in the 2022 ADRD Summit recommendations. Therefore, in Aim 1, we will assess AD/ADRD risk in patients with long-COVID using blood-based biomarkers (Abeta 1-40, Abeta 1-42, pTau181, NfL and GFAP) and determine whether APOE ε4 status, age, sex, race, ethnicity, and social determinants of health modify this risk. In Aim 2, we will investigate the associations of these blood-based biomarkers with MRI/MRS markers of neuroimflammation, neurodegeneration and cerebrovascular disease in patients with long-COVID and whether APOE ε4 status, age, sex, race, ethnicity, and social determinants of health modify these associations. The insights provided by this study will be critical for developing disease-modifying therapies targeting the underlying pathologic mechanisms associated with the long-term CNS consequences of COVID-19, including increased risk for AD/ADRD.