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

通过先进的 MR 成像和光谱学了解 COVID-19 对大脑的长期影响

• 批准号: 10712212
• 负责人: KEJAL KANTARCI
• 金额: $ 44.98万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712212
• 关键词: Acute; Address; Administrative Supplement; Affect; Age; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid beta-Protein; Anxiety; Attention; Behavioral; Biological Assay; Biological Markers; Biometry; Black race; Blood; Blood specimen; Brain; Budgets; COVID-19; COVID-19 impact; Central Nervous System; Cerebrovascular Disorders; Clinic; Clinical; Clinical Data; Collaborations; Communities; Data; Dementia; Diffusion Magnetic Resonance Imaging; Disease; Economic Factors; Enrollment; Ethnic Origin; Fatigue; Functional disorder; Funding; General Hospitals; Genetic Status; Geographic Factor; Glial Fibrillary Acidic Protein; Goals; Hispanic; Image; Imaging technology; Individual; Inflammatory; Institution; Interleukin-1; Interleukin-6; Laboratories; Latino; Long COVID; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Massachusetts; Measures; Medical History; Memory; Mental Depression; Methodist Church; Minnesota; Minority Enrollment; Minority Groups; Nerve Degeneration; Neurocognitive; Neurologic; Neurologic Symptoms; Neuropsychology; Nucleocapsid Proteins; Organ; Outcome; Participant; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Physical assessment; Predisposition; Procedures; Protocols documentation; Race; Recommendation; Recording of previous events; Research Institute; Research Personnel; Research Project Grants; Risk; Risk Assessment; SARS-CoV-2 infection; Sampling; Site; Sleep; Symptoms; TNF gene; Technology; Testing; Time; Underrepresented Minority; Universities; Vaccines; World Health Organization; antibody test; arterial spin labeling; bilingualism; blood-based biomarker; central nervous system injury; cohort; community engagement; comorbidity Index; coronavirus disease; dementia risk; demographics; executive function; follow-up; glial activation; inflammatory marker; insight; interest; long term consequences of COVID-19; longitudinal, prospective study; multimodality; neuroimaging; neuroinflammation; neuropathology; outreach; pandemic disease; parent grant; post SARS-CoV-2 infection; post-COVID-19; prospective; quantitative imaging; recruit; response; sex; social health determinants; specific biomarkers; stroke risk; symposium; targeted treatment

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.

项目总结/摘要 自世界卫生组织于二零二零年三月宣布COVID-19为大流行以来， 有证据表明，该疾病影响多个器官，包括中枢神经系统（CNS）。的 COVID BRAIN高级成像网络（COVID-BRAIN）的成立是为了阐明长期的CNS COVID-19的病理生理学。我们使用高度敏感，和谐， 先进的MR技术在3特斯拉询问神经炎症，神经变性和脑血管 SARS-CoV-2感染后持续性神经系统后遗症患者的疾病。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，马约诊所罗切斯特， 哈佛大学/马萨诸塞州总医院、约翰霍普金斯大学、休斯顿卫理公会研究所 研究所）收集纵向多模态MRI（T1、FLAIR、弥散MRI、磁共振加权MRI、单模态MRI）， 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 来自实验室确认的具有神经症状的COVID后病例的炎症性血液生物标志物数据 和匹配的对照。 与COVID-19相关的CNS损伤的病理生理成分可能导致 阿尔茨海默病及其相关痴呆症（AD/ADRD）的风险增加，如2022年ADRD中所强调的 首脑会议的建议。因此，在目标1中，我们将评估长期COVID患者的AD/ADRD风险 使用基于血液的生物标志物（Abeta 1-40、Abeta 1-42、pTau 181、NfL和GFAP），并确定是否 APOE ε4状态、年龄、性别、人种、种族和健康的社会决定因素改变了这种风险。在目标2中，我们将 研究这些基于血液的生物标志物与神经炎症的MRI/MRS标志物的相关性， 神经退行性疾病和脑血管病患者是否长期COVID和APOE ε4状态， 年龄、性别、种族、民族和健康的社会决定因素改变了这些关联。 这项研究提供的见解对于开发靶向的疾病修饰疗法至关重要。 与COVID-19的长期CNS后果相关的潜在病理机制， 包括AD/ADRD风险增加。