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.

项目总结