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

项目摘要/摘要 与其他患者相比，新冠肺炎患者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过急性中风的病例， 等等。建议。SARS-CoV-2感染对大脑的未知影响可能会影响目前的大脑功能和 预示着未来的神经变性和明显的神经功能障碍。然而，在没有已知基线的情况下 但是，由于病例和对照之间的正常差异会使亚临床效应的检测变得混乱。 因此，我们将利用大流行前详细的神经认知和成像评估来表征 一大批年轻患者的脑结构和功能的亚临床效应 轻微或无症状的SARS-CoV-2感染。我们将利用详细的血清学分析和 新的高度特异的SARS-CoV-2 T细胞检测可以确认以前感染过SARS-CoV-2，即使在 接种新冠肺炎的地点：(1)MILD新冠肺炎：35例实验室确诊的新冠肺炎患者， 未住院；(2)无症状：35人有SARS-CoV-2感染的实验室证据，但没有 新冠肺炎症状；(3)对照组：70名没有实验室或临床证据的匹配个体 SARS-CoV-2感染。所有参与者在新冠肺炎之前都很健康，没有合并危险因素或大脑 影像异常和神经认知功能正常。根据这一稳健的量化基线，我们将 通过重复包括大脑在内的一系列神经学评估来评估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 大流行。除了大流行前的基线外，我们还将评估参与者(1)在进入本计划时的情况 研究，(2)入职后6个月，(3)入职后18个月和(3)入职后3年，以解决以下问题： 目的1脑组织效应：表征脑缺血后宏观/微观结构和功能连接的变化。 在感染了SARS-CoV-2的患者和未感染的对照中，疫情持续了三年。 目的2功能效应：评估SARS-CoV-2大流行前神经认知功能的变化 患者，以及未感染的对照组，超过三年，同时考虑到情绪、压力和社会孤立。 目标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，修改SARS-CoV-2感染与MRI和神经认知变化的关联。 确认轻度SARS-CoV-2患者的神经系统疾病将对筛查、护理和随访具有关键意义。 在高危人群中出现大脑功能障碍。否则，这些问题将不会被发现，尽管存在潜在的 对于长期的、尚未被认识到的发病率。我们现有的样本以前是健康的，年轻的，种族多样的 来自高发和高发地区的女性和男性，在新冠肺炎之前有很好的特征 SARS-CoV-2大流行使我们能够确定SARS-CoV-2引起的亚临床脑损伤和功能障碍的特征。

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.