Mechanisms underlying COVID-19 induced Neurocognitive Dysfunction

COVID-19 诱发神经认知功能障碍的机制

• 批准号: 10736414
• 负责人: PAUL E SCHULZ
• 金额: $ 63.96万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736414
• 关键词: 2019-nCoV; Address; Age; Anatomy; Anti-Inflammatory Agents; Anxiety; Attention; Basic Science; Biological Markers; Blood; COVID-19; COVID-19 impact; COVID-19 mortality; Cerebrospinal Fluid; Characteristics; Cognitive; Data; Development; Disease; Distress; Elderly; Ethnic Origin; Exhibits; Female; Functional disorder; Goals; Hospitalization; Hospitals; Image; Immunoglobulin Therapy; Immunosuppressive Agents; Impaired cognition; Infection; Inflammation; Inflammatory; Infrastructure; Institution; Intervention; Intravenous Immunoglobulins; Lead; Learning; Link; Medical; Medical Records; Memory; Mental Depression; Mood Disorders; Neurocognitive; Neurocognitive Deficit; Neurologic; Neurologic Symptoms; Neurons; Neuropsychological Tests; Participant; Pathway interactions; Patients; Peripheral; Persons; Plasma Exchange; Positron-Emission Tomography; Probability; Quality of life; Race; Reporting; Research Personnel; Risk; Risk Factors; Role; SARS-CoV-2 infection; Screening procedure; Serum; Stress; Stroke; Survivors; Testing; Thick; Time; Translational Research; Underrepresented Populations; Work; biobank; brain size; cognitive change; cognitive testing; cohort; comorbidity; comparison control; coronavirus disease; digital; executive function; functional disability; global health; gray matter; infection rate; inflammatory marker; innovation; neuroinflammation; neuropsychiatric disorder; neuropsychiatry; older patient; pandemic disease; participant enrollment; post-COVID-19; processing speed; prospective; screening; severe COVID-19; sex; tau-1; therapy design; verbal

PROJECT SUMMARY/ABSTRACT Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, which causes Coronavirus Disease 2019 (COVID-19), has become a global health crisis. To date, more than 6.5 million deaths from COVID-19 have been reported worldwide. Amongst survivors, neurocognitive dysfunction and neuropsychiatric disorders, such as anxiety and depression, are increasingly recognized and can persist for months, or even years. This enduring neurocognitive and neuropsychiatric distress obligates us to address critical questions about their duration, risk factors, and underlying mechanisms. The goal of this project is to test the hypothesis that SARS-CoV-2 promotes cognitive decline in subjects who were previously normal via stimulating inflammatory pathways, with the greatest risk being in older adults, females, and those from underrepresented groups. We propose to utilize patients in our biorepository, who were hospitalized with SARS-CoV-2 infection, to achieve three Specific Aims: (1) to determine the type and duration of neurocognitive dysfunction present; (2) to ascertain risk factors for ongoing cognitive decline, including sex, age, race/ethnicity and comorbidities; and, (3) to verify that persistent neuroinflammation underlies cognitive decline. To achieve these Aims, our team has established a well-curated, highly diverse biorepository of more than 650 patients hospitalized with COVID-19. About 15% have succumbed to COVID-related illnesses; however, 37% have continued to return for testing at 3-6 and 12-months post hospitalization. Preliminary data demonstrates that 30% of subjects returning at one year show progressive cognitive decline, which is associated with elevated markers of inflammation and neuronal stress. Here we propose to follow these patients and perform detailed cognitive testing and assess biomarkers from their blood- serum, spinal fluid, and imaging to explicate the type and time course of cognitive changes present, the risk factors associated with cognitive dysfunction, and whether inflammation-induced neuronal distress underlies progressive neurocognitive impairment. This proposal is innovative because we are evaluating the long-term neurocognitive consequences of severe COVID-19 from a cohort that we have followed since the onset of the pandemic, which has provided preliminary data supporting our Aims. Moreover, we have brought together investigators with expertise in cognitive assessment and treatment, and basic and translational research, all in the setting of a strong institutional infrastructure. Our work is significant because understanding the role of persistent neuroinflammation in COVID-19-induced cognitive dysfunction will greatly enhance our ability to rationally test immunosuppressants for this very debilitating disorder.

项目摘要/摘要 严重的急性呼吸道综合征冠状病毒2（SARS-COV-2）感染，引起冠状病毒病 2019年（Covid-19）已成为全球健康危机。迄今为止，Covid-19的650万人死亡已有 据报道全球。在幸存者中，神经认知功能障碍和神经精神疾病，此类 随着焦虑和抑郁症的认可，可以持续数月甚至数年。这个持久 神经认知和神经精神障碍有义务解决有关其持续时间，风险的关键问题 因素和基本机制。该项目的目的是检验SARS-COV-2促进的假设 以前通过刺激炎症途径正常的受试者的认知能力下降， 在老年人，女性以及来自代表性不足的群体中的最大风险。我们建议利用 我们的生物疗法患者患有SARS-COV-2感染，以实现三个特定的目标： （1）确定存在神经认知功能障碍的类型和持续时间； （2）确定风险因素 持续的认知能力下降，包括性别，年龄，种族/种族和合并症；和（3）验证该持久性 神经炎症是认知能力下降的基础。为了实现这些目标，我们的团队已经建立了一个经过精心策划的 高度多样化的生物措施，有650多名Covid-19的住院患者。大约15％屈服了 与共同相关的疾病；但是，有37％的人继续在3-6和12个月的时间内返回测试 住院。初步数据表明，一年返回的受试者中有30％显示出渐进式 认知能力下降，这与炎症和神经元压力的标记升高有关。我们在这里 建议跟随这些患者并进行详细的认知测试，并从其血液中评估生物标志物 血清，脊髓液和成像以解释存在认知变化的类型和时间过程，风险 与认知功能障碍相关的因素，以及炎症引起的神经元障碍是否构成 进行性神经认知障碍。该提议具有创新性，因为我们正在评估长期 自从我们遵循以来，我们已经遵循的同类群体对神经认知的后果 大流行，提供了支持我们目标的初步数据。而且，我们已经团结在一起 具有认知评估和治疗方面的专业知识以及基础和转化研究的研究者 强大的机构基础设施的设置。我们的工作很重要，因为了解 COVID-19引起的认知功能障碍中持续的神经炎症将大大增强我们的能力 合理地测试这种非常衰弱的疾病的免疫抑制剂。