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

项目摘要 目前，全球有超过1400万例COVID-19确诊病例，其中超过3.7 仅在美国就有100万例确诊病例。早期出现的神经系统疾病之一 COVID-19重症患者的症状是精神状态改变或谵妄。 谵妄，定义为一种急性注意力和认知障碍，是一种常见的，危及生命的疾病， 临床综合征谵妄与认知能力的加速下降有关， 揭示潜在的脆弱性，由于预先存在的痴呆症病理在那些谁做 没有痴呆或轻度受损。在本申请中，我们提出i）识别基线 与谵妄相关的临床风险因素和血液生物标志物（具体目标1）， ii）确定临床风险因素、血液生物标志物和住院期间 COVID-19患者的谵妄伴未来认知能力下降（具体目标2）。 对于这个提议，我们将进行一系列认知测试， 出院后6个月通过电话进行测量。认知测试结果将是 由具有认知评估专业知识的研究者进行审查和裁定。临床风险 通过电子健康记录获得的炎症因子和血液生物标志物将被 用于确定基线易感因素与住院期间 谵妄（具体目标1）。然后，临床危险因素、血液炎症 生物标志物、6个月时院内谵妄的发生率和认知结局将 具体目标（1）。 本提案将描述潜在的血液生物标志物，用于医院内发生 谵妄，这可能允许成本效益的干预措施，以防止谵妄的实施。 此外，该提案将允许初步数据收集，以帮助我们进一步了解 受COVID-19影响最大的认知领域。这反过来又将告知我们的设计， 有效的长期随访研究，以减轻患者负担。项目数据将 还允许识别可能需要早期临床干预的高风险患者， 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.