Post-Acute Sequelae of SARS-CoV-2 Infection and Subsequent Disease Progression in Individuals with AD/ADRD: Influence of the Social and Environmental Determinants of Health

AD/ADRD 患者 SARS-CoV-2 感染的急性后遗症和随后的疾病进展：健康的社会和环境决定因素的影响

• 批准号: 10751275
• 负责人: Jiang Bian
• 金额: $ 256.15万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751275
• 关键词: 2019-nCoV; Acute; Adoption; Advanced Development; Air Pollution; Alabama; Alzheimer' s Disease; Alzheimer' s disease related dementia; Antigens; COVID-19; COVID-19 diagnosis; COVID-19 impact; Clinical; Clinical Data; Cognition Disorders; Cognitive; Complex; Connecticut; Data; Data Sources; Dementia; Disease Progression; Electronic Health Record; Environment; Epidemiology; Exposure to; Florida; Future; General Population; Health; Heterogeneity; Impaired cognition; Incidence; Individual; Knowledge; Laboratories; Link; Massachusetts; Measures; Medical History; Medicine; Memory Disorders; Methods; Modeling; Nature; Neighborhoods; Neurologic; Neurological outcome; New Hampshire; New Jersey; New York; Pathway interactions; Patients; Pattern; Phenotype; Play; Polymerase Chain Reaction; Positioning Attribute; Post-Acute Sequelae of SARS-CoV-2 Infection; Pragmatic clinical trial; Predisposition; Prevention strategy; Publishing; Research; Risk; Risk Factors; Role; SARS-CoV-2 positive; Selection Bias; Severities; Social Environment; Syndrome; Testing; Vital Statistics; Work; body system; causal model; cohort; coronavirus disease; data registry; deep learning; deprivation; electronic health record system; health determinants; mild cognitive impairment; mortality; neurologic sequelae of COVID-19; novel; pandemic disease; repository; routine care; social; social influence; success; treatment strategy; walkability

PROJECT SUMMARY The global pandemic of the 2019 novel coronavirus disease (COVID-19) has severe consequences. Recent studies showed that individuals with COVID-19 had increased risk of an array of postacute incident neurologic sequelae, including cognition and memory disorders, in 12 months after COVID-19 diagnosis. Despite elevated risks of postacute neurologic outcomes of COVID-19 observed in the general population, little is known about Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) in cognitively impaired individuals (e.g., those with mild cognitive impairment [MCI] and Alzheimer’s disease [AD]/AD-related dementias [ADRD]) and how it may impact their subsequent disease progression. The rapid adoption of electronic health record (EHR) systems has made longitudinal clinical data available for research, especially for individuals with MCI or AD/ADRD who engage in frequent routine care. However, existing large EHR-based COVID-19 cohorts do not specifically focus on cognitively impaired individuals have several key limitations, including (1) missing or inaccurate information on cognitive impairment, (2) challenges to characterize disease progression in individuals with MCI or AD/ADRD, and (3) robust causal modeling approaches that can account for the complex confounding and selection biases in observational RWD. More importantly, little is known about factors contributing to PASC and subsequent disease progression in cognitively impaired individuals with COVID-19. It has long been recognized that social and environmental determinants of health (SEDH) play important roles in cognitive health. Exposures to multiple SEDH have been associated with MCI and AD/ADRD. Our recent studies (R21ES032762 and the RECOVER Initiative) also found that SEDH are associated with COVID-19 incidence, severity, mortality, and PASC in the general population. Individuals are exposed to multiple SEDH simultaneously, and the exposome is an ideal framework to rigorously examine how SEDH impacts cognitively impaired individuals’ susceptibility to PASC and subsequent disease progression. Building upon our prior and ongoing work on COVID-19 and PASC in the general population with the RECOVER Initiative, sub-phenotyping and disease progression modeling, and multiple SEDH, we will (1) understand the epidemiology of PASC in individuals with MCI or AD/ADRD with high-throughput causal inference approaches, (2) examine the impacts of COVID-19 and PASC on subsequent disease progression in individuals with MCI or AD/ADRD with a novel dynamic topic modeling approach, and (3) assess how SEDH contribute to PASC and subsequent disease progression in individuals with MCI or AD/ADRD with the exposome conceptual framework. This project will fill important knowledge gaps on our understanding of, especially SEDH’s contributions to, risks of PASC and subsequent disease progression in individuals with cognitive impairment.

项目概要 2019 年新型冠状病毒病（COVID-19）的全球大流行造成了严重后果。 研究表明，患有 COVID-19 的个体发生一系列急性事件后神经系统疾病的风险增加 尽管在确诊 COVID-19 后 12 个月内出现了后遗症，包括认知和记忆障碍。 在普通人群中观察到的 COVID-19 急性后神经系统结果风险升高，但很少有研究表明 已知认知障碍个体（例如， 患有轻度认知障碍 [MCI] 和阿尔茨海默病 [AD]/AD 相关痴呆 [ADRD] 的患者）以及 它如何影响他们随后的疾病进展。电子健康记录 (EHR) 的快速采用。 系统已为研究提供了纵向临床数据，特别是对于患有 MCI 或 经常进行常规护理的 AD/ADRD 然而，现有的基于 EHR 的大型 COVID-19 队列却没有。 专门关注认知障碍人士有几个关键局限性，包括（1）缺失或 关于认知障碍的不准确信息，(2) 描述疾病进展特征的挑战 患有 MCI 或 AD/ADRD 的个体，以及 (3) 稳健的因果建模方法，可以解释 更重要的是，我们对观察性 RWD 中复杂的混杂因素和选择偏差知之甚少。 导致认知障碍患者 PASC 和随后疾病进展的因素 人们早已认识到，COVID-19 的社会和环境健康决定因素 (SEDH) 发挥着重要作用。 暴露于多种 SEDH 与 MCI 和认知健康有关。 AD/ADRD。我们最近的研究（R21ES032762 和 RECOVER Initiative）还发现 SEDH 与一般人群中的 COVID-19 发病率、严重程度、死亡率和 PASC 相关。 同时暴露于多个 SEDH，暴露组是严格检查如何 SEDH 影响认知障碍个体对 PASC 的易感性以及随后的疾病进展。 基于我们之前和正在进行的针对普通人群的 COVID-19 和 PASC 工作 RECOVER 计划、亚表型分析和疾病进展建模以及多个 SEDH，我们将 (1) 了解具有高通量因果关系的 MCI 或 AD/ADRD 个体中 PASC 的流行病学 推理方法，(2) 检查 COVID-19 和 PASC 对后续疾病进展的影响 患有 MCI 或 AD/ADRD 的个体采用新颖的动态主题建模方法，以及 (3) 评估 SEDH 如何 有助于 MCI 或 AD/ADRD 个体的 PASC 和随后的疾病进展 该项目将填补我们理解的重要知识空白， 特别是 SEDH 对患有 PASC 的风险和随后疾病进展的个体的贡献 损害。