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

项目摘要 本R21探索/发展研究助学金是根据PAR-20-177的要求编写的： 紧急奖：对严重急性呼吸系统综合症冠状病毒2的快速调查 (SARS-CoV-2)和冠状病毒病2019(新冠肺炎)。SARS-CoV2是一种 引起新冠肺炎，并已知与血管紧张素转换具有高亲和力结合 酶2(ACE-2)受体。这种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。 大脑。SARS-CoV2病毒被证明是神经侵袭性的，但无论它是导致持续性还是 残留的神经炎症或神经元损伤尚不清楚。我们将使用多参数核磁共振 新冠肺炎患者神经炎症和神经完整性标志物的评估方法 以及全面的NIH工具箱®和PROMIS®电池来评估认知表现， 康复期患者的情绪困扰、疲劳、疼痛、运动功能和全球健康结局 新冠肺炎患者。我们还将测定血清和脑脊液(CSF)水平 神经炎性标志物，即细胞因子和趋化因子，可以预测神经成像 和行为测量。我们提出了三个具体目标：目标1：结构磁共振、质子 波谱(1H-MRS)和弥散张量成像(DTI)将用于评估区域 新冠肺炎恢复期患者和健康对照组的神经炎症或神经元损伤 新冠肺炎检测呈阴性。目标2：认知和运动功能将使用 NIH Toolbox®，同时将使用以下工具评估情绪困扰、疲劳、疼痛和整体健康 Promis®。这些行为的神经相关性也将通过血液氧合进行评估。 水平依赖功能磁共振成像(BOLD-fMRI)。目标3：脑脊液和血液将在 应用多重酶联免疫吸附试验对早期恢复期炎症的可溶性物进行量化 细胞因子面板。D-二聚体和C-反应蛋白水平也将被重复，以比较 在患者急性住院期间获得的。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 新冠肺炎患者。我们还将调查这种大脑异常是否可能与 可能影响他们整体健康的认知或行为结果。此外，我们还将 确定可溶性炎性标志物夜间是否可预测大脑或神经行为 结果。这些研究的发现可能会导致一项更大规模的研究，这可能会指导未来 新冠肺炎患者改善神经元损伤或神经炎症的治疗。

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.