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

项目总结 2019年新型冠状病毒病(新冠肺炎)的全球大流行后果严重。近期 研究表明，新冠肺炎携带者患一系列急性事件后神经系统疾病的风险增加 后遗症，包括认知和记忆障碍，在新冠肺炎确诊后12个月内。尽管 在普通人群中观察到新冠肺炎急性后神经后果的风险增加，几乎没有 已知认知受损个体感染SARS-CoV-2(PASC)的急性后遗症(例如， 有轻度认知障碍[MCI]和阿尔茨海默病[AD]/AD相关痴呆[ADRD]的人)和 它可能会如何影响他们随后的疾病进展。电子健康档案(EHR)的迅速采用 系统已经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，现有的基于电子病历的大型新冠肺炎队列并不 特别关注认知受损的人有几个关键限制，包括(1)失踪或 关于认知障碍的不准确信息，(2)表征疾病进展的挑战 MCI或AD/ADRD患者，以及(3)稳健的因果建模方法，可以解释 观察性RWD中的复杂混杂和选择偏差。更重要的是，人们对此知之甚少 认知受损患者的PASC和随后的疾病进展的因素 新冠肺炎。长期以来，人们已经认识到，社会和环境决定因素在健康中发挥着重要作用 在认知健康中的重要作用。暴露于多种SEDH与MCI和 AD/ADRD。我们最近的研究(R21ES032762和Recover Initiative)也发现SEDH是 与新冠肺炎在普通人群中的发病率、严重性、死亡率和PASC相关。个人是 同时暴露在多个SEDH中，曝光组是严格研究如何 SEDH影响认知受损的个体对PASC和随后的疾病进展的易感性。 在我们先前和正在进行的关于新冠肺炎和PASC的普通民众工作的基础上， 恢复倡议、亚表型和疾病进展建模，以及多SEDH，我们将(1) 了解MCI或AD/ADRD高通量病因患者中PASC的流行病学 推理方法，(2)检查新冠肺炎和PASC对随后的疾病进展的影响 MCI或AD/ADRD患者使用新的动态主题建模方法，以及(3)评估SEDH MCI或AD/ADRD患者的PASC和随后的疾病进展 揭示概念框架。这个项目将填补我们在理解、 尤其是SEDH对PASC和随后疾病进展的风险的贡献 认知障碍。

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.