Characterizing persistent subclinical neurobehavioral effects of COVID-19 in a diverse urban population

项目总结/摘要 与其他人相比，在COVID-19的老年幸存者中发现了过度的认知功能障碍。 呼吸道感染因此，SARS-CoV-2对大脑的不利影响可能超出急性中风的情况， 等结果显示SARS-CoV-2感染对大脑的影响可能会影响当前的大脑功能， 预示着未来的神经退化和明显的神经功能障碍。然而，由于缺乏已知的基线， 在功能方面，亚临床效应的检测将被病例和对照之间的正常变化混淆。 因此，我们将利用大流行前详细的神经认知和成像评估， 在一个大型的年轻患者队列中， 轻度或无症状SARS-CoV-2感染。我们将利用详细的血清学分析确定3组， 新的高度特异性SARS-CoV-2 T细胞检测，即使在 COVID-19疫苗接种背景：（1）儿童COVID-19：35例实验室确诊的COVID-19患者， 未住院;（2）无症状：35例有SARS-CoV-2感染的实验室证据，但无 COVID-19症状;和（3）对照组：70名匹配的个体，无既往实验室或临床证据 SARS-CoV-2感染。所有参与者在COVID-19之前都是健康的，没有共病风险因素或大脑 影像学异常和神经认知功能正常。根据这一稳健的量化基准，我们将 通过重复一系列神经系统评估来评估SARS-CoV-2感染引起的变化， 神经认知功能、情绪、焦虑、压力和社交孤立的成像和评估， 流行病除了他们在大流行前的基线外，我们还将在参与者（1）进入本拟议的 研究，（2）入组后6个月，（3）入组后18个月和（3）入组后3年，以解决以下问题： 目的1脑组织效应：表征脑组织宏观/微观结构和功能连接的变化， 大流行，在SARS-CoV-2感染的患者和未感染的对照组中，超过三年。 目的2功能影响：评估SARS-CoV-2患者神经认知功能较大流行前的变化 患者和未感染的对照组，在三年内，同时考虑情绪，压力和社会孤立。 目的3个体风险因素[探索性]：探索个体特征，如性别、BMI、SES 和种族/民族，改变SARS-CoV-2感染与MRI和神经认知变化的关联。 预测轻度SARS-CoV-2的神经系统发病率将对筛查、护理和随访产生关键影响- 有脑功能障碍风险的人群否则，尽管存在潜在的风险， 长期的，尚未被认识的疾病。我们现有的样本，以前健康，年轻，种族多样 来自高流行率和高发病率地区的女性和男性，在COVID-19之前特征良好 大流行，使我们能够独特地表征SARS-CoV-2引起的亚临床脑损伤和功能障碍。

PROJECT SUMMARY/ABSTRACT Excess cognitive dysfunction has been identified in older adult survivors of COVID-19, compared to other respiratory infections. SARS-CoV-2 may thus adversely impact the brain beyond what the cases of acute stroke, etc. suggest. Unrecognized brain effects of SARS-CoV-2 infection may impact current brain functioning and presage future neurodegeneration and overt neurologic dysfunction. However, absent known baseline functioning, detection of subclinical effects will be confounded by normal variation between cases and controls. We will therefore leverage detailed pre-pandemic neurocognitive and imaging assessments to characterize subclinical effects on brain structure and function among a large cohort of younger patients who experienced mild or asymptomatic SARS-CoV-2 infection. We will identify 3 groups utilizing detailed serologic analysis and novel highly specific SARS-CoV-2 T-cell assays to allow confirmation of prior SARS-CoV-2 infection, even in the setting of COVID-19 vaccination: (1) M ild COVID-19: 35 patients with laboratory confirmed COVID-19 who were NOT hospitalized; (2) Asymptomatic: 35 with laboratory evidence of SARS-CoV-2 infection, but no history of COVID-19 symptoms; and (3) Controls: 70 matched individuals without laboratory or clinical evidence of prior SARS-CoV-2 infection. All participants were healthy prior to COVID-19, with no comorbid risk factors or brain imaging abnormality and normal neurocognitive performance. Against this robust quantitative baseline, we will assess change due to SARS-CoV-2 infection by repeating a suite of neurological assessments, including brain imaging and assessments of neurocognitive function, mood, anxiety, stress and social isolation due to the pandemic. In addition to their pre-pandemic baseline, we will assess participants (1) at entry into this proposed study, (2) 6 months after entry, (3) 18 months after entry and (3) three years after entry, to address the following: Aim 1 Brain Tissue Effects: Characterize change of macro/microstructure and functional connectivity frompre- pandemic, among SARS-CoV-2 infected patients and non-infected controls, over three years. Aim 2 Functional Effects: Assess change in neurocognitive function from pre-pandemic, among SARS-CoV-2 patients, and in non-infected controls, over three years, while accounting for mood, stress and social isolation. Aim 3 Individual Risk Factors [Exploratory]:Explore whether individual characteristics, such as sex, BMI, SES and race/ethnicity, modify the associations of SARS-CoV-2 infection with MRI and neurocognitive changes. Confirming neurological morbidity in mild SARS-CoV-2 will have key implications for screening, care and follow- up for brain dysfunction among those at risk. Theseproblems would otherwise go unrecognized, despite potential for long-term, yet-unrecognized morbidity. Our existing sample of previously healthy, young, ethnically diverse women and men from a high prevalence and high morbidity region, well-characterized prior to the COVID-19 pandemic, uniquely positions us to characterize subclinical brain injury and dysfunction due to SARS-CoV-2.