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 这项R21探索性/发展研究赠款是根据Par-20-177的响应而写的： 紧急奖项：严重急性呼吸综合征冠状病毒2的快速调查2 （SARS-COV-2）和冠状病毒疾病2019（COVID-19）。 SARS-COV2是病毒 导致COVID-19，并且已知与血管紧张素覆盖具有高亲和力结合 酶2（ACE-2）受体。该受体在内皮衬里，先天免疫中表达 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 脑。 SARS-COV2病毒被证明具有神经侵染，但无论是导致持久性还是 残留的神经炎症或神经元损伤尚不清楚。我们将使用多参数MRI 评估Covid-19患者中神经炎症和神经整合性标记的方法， 以及全面的NIHToolbox®和Promis®电池，以评估认知性能， 情绪困扰，疲劳，疼痛，运动功能和康复中全球健康结果 Covid-19患者。我们还将确定血清和脑脊液（CSF）水平是否 神经炎症标志物（即细胞因子和趋化因子）的神经影像学预测 和行为测量。我们提出了三个具体目标：目标1：结构MRI，质子 光谱（1H-MR）和扩散张量成像（DTI）将用于评估区域 康复期COVID-19患者和健康对照中的神经炎症或神经元损伤 进行阴性COVID-19测试。 AIM 2：将使用认知和运动功能进行评估 NIHToolbox®虽然情绪困扰，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通过血液充 依赖性功能的MRI（BOLD-FMRI）。 AIM 3：CSF和血液将在 早期康复以使用多重ELISA量化炎症的固体标记 细胞因子面板。还将重复进行D二二聚体和C反应蛋白的水平 那些在患者急性住院期间获得的。该项目将生成新的数据 关于康复中可能的残留或持续神经炎症或脑损伤 Covid-19患者。我们还将调查这种大脑异常是否可能相关 可能会影响其整体健康状况的认知或行为结果。此外，我们会的 确定固体炎症标志物是否预测大脑还是神经行为 结果。这些研究的发现可能会导致更大的研究，以指导未来 改善COVID-19患者的神经元损伤或神经炎症的治疗方法。