Clinical and Biological Predictors of Delirium and Long-term Cognitive Outcomes in COVID19 Patients

项目摘要 目前，全球有1400多万例新冠肺炎确诊病例，其中370多例 仅在美国就有100万确诊病例。最早出现的神经病学之一 新冠肺炎危重患者的症状是精神状态改变，或称精神错乱。 精神错乱，定义为注意力和认知的急性障碍，是一种频繁的、危及生命的疾病。 临床综合征。精神错乱与认知衰退的加速有关，也可能 揭开那些患有痴呆症的人因既往痴呆病理而导致的潜在脆弱性 没有患上痴呆症或轻度受损。在本申请中，我们建议i)确定基线 与精神错乱相关的临床危险因素和血液生物标记物(具体目标1)和 二)确定临床危险因素、血液生物标记物和住院患者之间的联系 新冠肺炎患者的精神错乱和未来的认知能力下降(特定目标2)。 对于这项提案，我们将进行一系列认知测试和自我报告 出院后6个月通过电话进行测量。认知测试结果将会是 由具有认知评估专业知识的调查人员进行审查和裁决。临床风险 通过电子健康记录可以获得的炎症因子和血液生物标志物将是 用于确定基线易感因素与住院之间的关联 精神错乱(特定目标1)。然后，临床危险因素与血液炎症之间的关系 生物标志物、院内精神错乱的发生和6个月后的认知结果将是 确定(具体目标1)。 这项提案将表征潜在的血液生物标记物，用于医院内发生 精神错乱，这可能允许以成本效益的方式实施干预措施，以防止精神错乱。 此外，这项建议将允许初步收集数据，以帮助加深我们的理解 受新冠肺炎影响最大的认知领域。反过来，这将为我们的设计提供一个 有效的长期随访研究，减轻患者负担。来自拟议项目的数据将 还允许识别可能需要早期临床干预的高危患者 认知问题。

Project Summary Currently, there are over 14 million confirmed cases of COVID-19 globally with over 3.7 million confirmed cases in the United States alone. One of the early presenting neurological symptoms of individuals who are critically ill from COVID-19 is altered mental status, or delirium. Delirium, defined as an acute disorder of attention and cognition, is a frequent, life-threatening clinical syndrome. Delirium has been linked to acceleration of cognitive decline, and may also be unmasking underlying vulnerability due to pre-existing dementia pathology in those who do not have dementia or are mildly impaired. In this application, we propose i) to identify baseline clinical risk factors and blood biomarkers that are associated with delirium (Specific Aim 1) and ii) to determine the association between clinical risk factors, blood biomarkers, and in-hospital delirium with future cognitive decline in patients with COVID-19 (Specific Aim 2). For this proposal, we will administer a battery of cognitive tests and self-reported measures by phone at 6 months following hospital discharge. Cognitive test results will be reviewed and adjudicated by investigators with expertise in cognitive assessments. Clinical risk factors and blood biomarkers of inflammation available through electronic health records will be used to determine the association between baseline predisposing factors and in-hospital delirium (Specific Aim 1). Then, the association between clinical risk factors, blood inflammatory biomarkers, occurrence of in-hospital delirium and cognitive outcome at 6 months will be determined (Specific Aim 1). This proposal will characterize potential blood biomarkers for in-hospital occurrence of delirium, which may allow cost-effective implementation of interventions to prevent delirium. Additionally, this proposal will allow preliminary data collection to help further our understanding of the cognitive domains most impacted by COVID-19. This, in turn, will inform our design of an efficient long-term follow-up study to reduce patient burden. Data from the proposed project will also allow identification of high-risk patients who may need earlier clinical intervention for cognitive problems.