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.

项目概要 此 R21 探索性/发展性研究补助金是为了响应 PAR-20-177 而编写的： 紧急奖项：严重急性呼吸系统综合症冠状病毒 2 型快速调查 (SARS-CoV-2) 和 2019 年冠状病毒 (COVID-19) 是病毒。 引起 COVID-19，并且已知与血管紧张素覆盖物具有高亲和力结合 酶 2 (ACE-2) 受体 该受体在内皮衬里表达，具有先天免疫功能。 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 SARS-CoV2 病毒被证明具有神经侵袭性，但它是否会导致持续性或 残余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 患者神经炎症和神经完整性标志物的方法， 以及用于评估认知表现的综合 NIH Toolbox® 和 PROMIS® 电池， 康复者的情绪困扰、疲劳、疼痛、运动功能和全球健康结果 我们还将确定 COVID-19 患者的血清和脑脊液 (CSF) 水平。 神经炎症标记物，即细胞因子和趋化因子，可以预测神经影像学 我们提出了三个具体目标： 目标 1：结构 MRI、质子。 光谱（1H-MRS）和扩散张量成像（DTI），将用于评估区域 恢复期 COVID-19 患者和健康对照者的神经炎症或神经元损伤 COVID-19 测试呈阴性 目标 2：将使用以下指标评估认知和运动功能。 NIH Toolbox®，而情绪困扰、疲劳、疼痛和整体健康状况将使用以下方法进行评估 PROMIS® 还将通过血氧评估评估这些行为的神经相关性。 水平依赖性功能 MRI (BOLD-fMRI) 目标 3：期间收集脑脊液和血液。 使用多重 ELISA 量化早期康复期炎症的可溶性标志物 D-二聚体和 C-反应蛋白的水平也将重复进行比较。 该项目将产生新的数据。 关于恢复期可能残留或持续的神经炎症或脑损伤 我们还将调查这种大脑异常是否与 COVID-19 患者有关。 此外，我们还将关注可能影响他们整体健康的认知或行为结果。 确定可溶性炎症标记物是否可以预测大脑或神经行为 这些研究的结果可能会导致更大规模的研究，从而指导未来的结果。 改善 COVID-19 患者神经元损伤或神经炎症的治疗。

项目成果

Neuronal and Glial Metabolite Abnormalities in Participants With Persistent Neuropsychiatric Symptoms After COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study.

COVID-19 后患有持续性神经精神症状的参与者的神经元和神经胶质代谢异常：一项脑质子磁共振波谱研究。

• 发表时间: 2023-11-28
• 作者: Ernst, Thomas;Ryan, Meghann C;Liang, Hua;Wang, Justin P;Cunningham, Eric;Saleh, Muhammad G;Kottilil, Shyamasundaran;Chang, Linda
• 通讯作者: Chang, Linda

Changes in Brain Activation Patterns During Working Memory Tasks in People With Post-COVID Condition and Persistent Neuropsychiatric Symptoms.

患有新冠肺炎后状况和持续神经精神症状的人在工作记忆任务期间大脑激活模式的变化。

• 发表时间: 2023-06-06
• 影响因子: 9.9
• 作者: Chang, Linda;Ryan, Meghann C;Liang, Huajun;Zhang, Xin;Cunningham, Eric;Wang, Justin;Wilson, Eleanor;Herskovits, Edward H;Kottilil, Shyamasundaran;Ernst, Thomas M
• 通讯作者: Ernst, Thomas M

Quantifying the Neuropsychiatric Symptoms in Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox® and PROMIS.

使用 NIH Toolbox® 和 PROMIS 量化 COVID-19 急性后遗症 (PASC) 的神经精神症状。

• 发表时间: 2023-06-20
• 作者: Ryan, Meghann C;Liang, Huajun;Wilson, Eleanor;Levine, Andrea;Kottilil, Shyamasundaran;Ernst, Thomas;Chang, Linda
• 通讯作者: Chang, Linda