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

表征 COVID-19 对不同城市人群的持续亚临床神经行为影响

• 批准号: 10580856
• 负责人: Johanna Patricia Daily
• 金额: $ 69.09万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580856
• 关键词: 2019-nCoV; Address; Anxiety; Area; Attention; Body mass index; Brain; Brain Injuries; Brain imaging; Brain region; COVID-19; COVID-19 impact; COVID-19 pandemic; COVID-19 patient; COVID-19 survivors; COVID-19 vaccination; Caring; Cellular Assay; Characteristics; Clinical; Data; Detection; Disadvantaged minority; Elderly; Enrollment; Ethnic Origin; Exhibits; Functional disorder; Future; Healthcare; High Prevalence; Hypoxia; Iceberg; Image; Impaired cognition; Individual; Infection; Influenza; Injury; Laboratories; Magnetic Resonance Imaging; Measures; Minority Groups; Moods; Morbidity - disease rate; Nature; Nerve Degeneration; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neurologic Dysfunctions; New York City; Participant; Patients; Performance; Persons; Populations at Risk; Positioning Attribute; Race; Recording of previous events; Reporting; Respiratory Tract Infections; Risk; Risk Factors; SARS-CoV-2 infection; Sampling; Serology; Short-Term Memory; Signal Transduction; Social isolation; Stress; Stroke; Structure; Symptoms; T-Lymphocyte; Thick; Urban Population; Variant; Woman; acute stroke; brain dysfunction; brain magnetic resonance imaging; brain tissue; brain volume; cohort; comorbidity; daily functioning; ethnic diversity; executive function; experience; follow-up; longitudinal design; men; neurobehavioral; neurocognitive test; neuroimaging; neuropsychiatry; novel; pandemic disease; post SARS-CoV-2 infection; pre-pandemic; public health relevance; racial diversity; screening; severe COVID-19; sex; study population; systemic inflammatory response; young man; young woman

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.

项目概要/摘要 与其他人相比，COVID-19 老年幸存者存在过度认知功能障碍 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病例、 等建议。 SARS-CoV-2 感染引起的未被识别的大脑影响可能会影响当前的大脑功能和 预示着未来的神经退行性变和明显的神经功能障碍。然而，缺乏已知的基线 功能，亚临床效应的检测将因病例和对照之间的正常差异而混淆。 因此，我们将利用详细的大流行前神经认知和影像评估来表征 对一大群年轻患者的大脑结构和功能产生亚临床影响 轻度或无症状的 SARS-CoV-2 感染。我们将利用详细的血清学分析确定 3 组 新型高度特异性的 SARS-CoV-2 T 细胞检测可以确认先前的 SARS-CoV-2 感染，即使是在 COVID-19 疫苗接种情况： (1) 轻度 COVID-19：35 名实验室确诊的 COVID-19 患者 没有住院； (2) 无症状：35 例，有 SARS-CoV-2 感染实验室证据，但无感染史 2019冠状病毒病症状; (3) 对照：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 COVID-19 之前都很健康，没有合并症危险因素或大脑 影像学异常和正常的神经认知表现。根据这一稳健的定量基线，我们将 通过重复一系列神经学评估（包括大脑评估）来评估 SARS-CoV-2 感染引起的变化 神经认知功能、情绪、焦虑、压力和社会孤立的成像和评估 大流行。除了大流行前的基线之外，我们还将在进入本提议时评估参与者 (1) 研究，(2) 入境后 6 个月，(3) 入境后 18 个月，(3) 入境后三年，以解决以下问题： 目标 1 脑组织效应：表征从前到后的宏观/微观结构和功能连接的变化 三年来，SARS-CoV-2 感染患者和未感染对照人群中出现了大流行。 目标 2 功能影响：评估 SARS-CoV-2 与大流行前相比神经认知功能的变化 研究人员对患者和未感染对照进行了三年多的研究，同时考虑了情绪、压力和社会隔离。 目标 3 个人风险因素 [探索性]：探索个人特征，如性别、BMI、SES 是否存在 和种族/民族，改变 SARS-CoV-2 感染与 MRI 和神经认知变化的关联。 确认轻度 SARS-CoV-2 的神经发病率将对筛查、护理和随访产生重要影响。 为高危人群的大脑功能障碍做好准备。否则这些问题将不会被认识到，尽管有潜力 对于长期的、尚未认识到的发病率。我们现有的健康、年轻、种族多样化的样本 来自高流行率和高发病率地区的女性和男性，在 COVID-19 之前就已明确特征 大流行使我们能够独特地描述 SARS-CoV-2 引起的亚临床脑损伤和功能障碍。