Neuroimaging and Behavioral Studies to Assess For Neuroinflammation in COVID-19 During Convalescence

用于评估 COVID-19 康复期间神经炎症的神经影像学和行为研究

• 批准号: 10193009
• 负责人: LINDA CHANG
• 金额: $ 42.49万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10193009
• 关键词: 2019-nCoV; ACE2; Acute; Affect; Affinity; Age; Angiotensins; Anxiety; Attention; Award; Back; Basal Ganglia; Behavior; Behavioral; Binding; Blood; Brain; Brain Injuries; Brain imaging; Brain region; C-reactive protein; CCL2 gene; COVID-19; COVID-19 patient; COVID-19 test; Cells; Cerebrospinal Fluid; Choline; Cognitive; Cognitive deficits; Convalescence; Creatine; Data; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Emergency Situation; Emotions; Encephalitis; Endothelium; Enzyme-Linked Immunosorbent Assay; Enzymes; Fatigue; Fibrin fragment D; Functional Magnetic Resonance Imaging; Future; Globus Pallidus; Glutamates; Health; Hospitalization; Human; IL7 gene; IL8 gene; Immune; Inflammation; Inflammatory; Information Systems; Interferon Type II; Interleukin-1 beta; Interleukin-10; Interleukin-13; Interleukin-2; Interleukin-4; Interleukin-6; Investigation; Lead; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Mental Depression; Mental Health; Microglia; Motor; N-acetylaspartate; Neurocognitive; Neurological outcome; Neuronal Injury; Neurons; Outcome; Pain; Patient Outcomes Assessments; Patients; Performance; Phase; Proteins; Protons; Radial; Research Project Grants; Residual state; Resources; SARS-CoV-2 negative; Serum; Short-Term Memory; Socioeconomic Status; Spectrum Analysis; Structure; Symptoms; TNF gene; Techniques; Testing; Thalamic structure; United States National Institutes of Health; Viral; Virus; acute infection; behavior measurement; behavioral outcome; behavioral study; blood oxygen level dependent; brain abnormalities; brain volume; chemokine; circulating biomarkers; cognitive performance; cytokine; emotional distress; glial activation; global health; gray matter; inflammatory marker; information processing; macrophage; monocyte; myoinositol; neural correlate; neurobehavioral; neuroimaging; neuroinflammation; neuron loss; novel; pain symptom; physical conditioning; putamen; receptor; relating to nervous system; response; severe COVID-19; sex; standard of care; white matter

Project Summary This R21 Exploratory/Developmental Research Grant is written in response to PAR-20-177: Emergency Awards: Rapid Investigation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19). SARS-CoV2 is the virus that causes COVID-19, and is known to have high affinity binding to the angiotensin-coverting enzyme 2 (ACE-2) receptors. This receptor is expressed on endothelial lining, innate immune cells, including monocytes and macrophages, as well as astroglial and microglial cells in the brain. SARS-CoV2 virus was shown to be neuroinvasive, but whether it causes persistent or residual neuroinflammation or neuronal injury is unknown. We will use a multi-parametric MRI approach to evaluate markers of neuroinflammation and neural integrity in COVID-19 patients, and a comprehensive NIH Toolbox® and PROMIS® battery to assess cognitive performance, emotional distress, fatigue, pain, motor function and global health outcomes in convalescent COVID-19 patients. We will also determine whether serum and cerebrospinal fluid (CSF) levels of neuroinflammatory markers, i.e. cytokines and chemokines, would predict the neuroimaging and behavioral measures. We propose three specific Aims: Aim 1: Structural MRI, proton spectroscopy (1H-MRS) and diffusion tensor imaging (DTI), will be used to evaluate regional neuroinflammation or neuronal injury in convalescent COVID-19 patients and in healthy controls with negative COVID-19 tests. Aim 2: Cognitive and motor function will be evaluated using the NIH Toolbox®, while emotional distress, fatigue, pain and overall health will be assessed using PROMIS®. Neural correlates of these behaviors will also be assessed with blood oxygenation level dependent-functional MRI (BOLD-fMRI). Aim 3: CSF and blood will be collected during early convalescence to quantify soluble markers of inflammation using a multiplex ELISA cytokine panel. Levels of D-dimer and C-reactive protein will also be repeated to compare with those obtained during the patients’ acute hospitalization. This project will generate novel data regarding possible residual or ongoing neuroinflammation or brain injury in convalescent COVID-19 patients. We will also investigate whether such brain abnormalities might be related to cognitive or behavioral outcomes that might affect their overall health. Furthermore, we will determine whether the soluble inflammatory markers night predict brain or neurobehavioral outcomes. Findings from these studies can lead to a larger study that may guide future treatments to ameliorate neuronal injury or neuroinflammation in COVID-19 patients.

项目摘要 这个R21探索/发展研究补助金是为了回应PAR-20-177而写的： 紧急奖：严重急性呼吸系统综合征冠状病毒2的快速调查 （SARS-CoV-2）和2019冠状病毒病（COVID-19）。SARS-CoV 2是一种病毒， 引起COVID-19，并且已知与血管紧张素转化酶具有高亲和力结合， 酶2（ACE-2）受体。该受体表达于内皮细胞衬里，先天免疫 细胞，包括单核细胞和巨噬细胞，以及星形胶质细胞和小胶质细胞， 个脑袋SARS-CoV 2病毒被证明是神经侵袭性的，但它是否会导致持续性或 残留的神经炎症或神经元损伤是未知的。我们会用多参数核磁共振成像 评估COVID-19患者神经炎症和神经完整性标志物的方法， 以及一个全面的美国国立卫生研究院（NIH）和PROMIS电池来评估认知能力， 康复期患者的情绪困扰、疲劳、疼痛、运动功能和总体健康结果 新冠肺炎患者。我们还将确定血清和脑脊液（CSF）水平是否 神经炎性标志物，即细胞因子和趋化因子，可以预测神经影像学 和行为测量。我们提出了三个具体目标：目标1：结构MRI，质子 磁共振波谱（1H-MRS）和弥散张量成像（DTI）将用于评估区域 恢复期COVID-19患者和健康对照的神经炎症或神经元损伤 COVID-19检测呈阴性目标2：将使用以下方法评价认知和运动功能： 而情绪困扰，疲劳，疼痛和整体健康将使用 PROMIS®.这些行为的神经相关性也将与血氧进行评估 水平依赖功能磁共振成像（BOLD-fMRI）。目的3：在研究期间采集CSF和血液 使用多重ELISA对早期恢复期的可溶性炎症标志物进行定量 细胞因子组。还将重复检测D-二聚体和C-反应蛋白水平， 在患者急性住院期间获得的那些。这个项目将产生新的数据 关于恢复期患者可能残留或正在进行的神经炎症或脑损伤， 新冠肺炎患者。我们还将研究这种大脑异常是否与 认知或行为结果可能会影响他们的整体健康。此外，我们将 确定可溶性炎症标记物是否能预测大脑或神经行为 结果。这些研究的发现可以导致一个更大的研究，可能会指导未来的研究。 治疗以改善COVID-19患者的神经元损伤或神经炎症。