CORALE-SeroNet Project 1

CORALE-SeroNet 项目 1

• 批准号: 10222436
• 负责人: Jane C. Figueiredo
• 金额: $ 54.44万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222436
• 关键词: 2019-nCoV; Acute-Phase Proteins; Age; Antibodies; Antibody Response; Antigen-Antibody Complex; Asians; Autoimmune Diseases; Behavioral; Biological Response Modifiers; Blood Circulation; COVID-19; California; Cancer Patient; Catchment Area; Clinical; Complement; Conflict (Psychology); Data; Diabetes Mellitus; Diet; Eicosanoids; Elderly; Enrollment; Environment; Ethnic Origin; Exhibits; Exposure to; Geographic Locations; Health Personnel; Health system; Healthcare Systems; Heterogeneity; Hispanics; Household; Hypertension; Immune; Immunity; Immunoglobulin G; Immunoglobulin M; Individual; Individual Differences; Infection; Inflammation Mediators; Inflammatory; Inflammatory Response; Influenza; Infrastructure; Knowledge; Life Style; Lipids; Longitudinal cohort; Longitudinal cohort study; Maps; Measures; Mediator of activation protein; Metabolic; Methods; Minority; Molecular; Molecular Profiling; Morbidity - disease rate; Natural History; Nature; Obesity; Outcome; Participant; Patients; Pattern; Peripheral; Persons; Population; Population Heterogeneity; Populations at Risk; Predisposition; Race; Recovery; Recovery of Function; Reporting; Resistance; Resistance to infection; Resolution; Resources; Risk; Serological; Signal Transduction; Smoking; Socioeconomic Status; Symptoms; Testing; Therapeutic immunosuppression; Time; Variant; Viral; Woman; Work; aged; base; cancer therapy; clinical predictors; co-infection; cohort; comorbidity; cytokine; disorder risk; experience; high risk; immune reconstitution; infection risk; men; metropolitan; predictive signature; prospective; racial and ethnic; racial minority; response; sex; trait

ABSTRACT Pressing questions pertain to the consistently observed paradoxes regarding the variable nature of host susceptibility and response to SARS-CoV-2. We and others have reported on more active spread and greater morbidity among older persons and ethnic/racial minorities, especially with certain comorbidities and metabolic. To date the evidence to date suggests that while some individuals exhibit a particular vulnerability to SARS-CoV- 2 (i.e. susceptibility), many others have an intrinsic or acquired relative immunity (i.e. resistance) to infection or disease risk or both for unknown reasons. Further compounding the enigmatic nature of SARS-CoV-2 risk is the conflicting data on measures of immunity. We and others have found that the extent to which individuals exhibit a post-infectious IgG antibody response to SARS-CoV-2 is highly variable – many persons have no antibodies detected in the peripheral circulation within weeks to months following resolution of symptoms. We hypothesize that: (H1) the natural history of response to SARS-CoV-2 exposure is marked by discernible patterns of susceptibility vs resistance that vary by demographic, clinical, and host-environment factors; and, (H2) divergent clinical trajectories are driven by underlying inter-individual differences in the complex immune- inflammatory response to SARS-CoV-2 exposure. Based on early observations and emerging data, we anticipate four potential clinical trajectories among exposed individuals: (i) those with exposure, but apparently no infection; (ii) infection with minimal to no symptoms, then persistent immunity; (ii) infection with symptoms, recovery, persistent immunity; and, (iv) infection, recovery, re-infection. To test these hypotheses, we propose to leverage our existing CORALE study (n=10,370), a prospective longitudinal cohort study at a major metropolitan healthcare system in Southern California. Our catchment area includes large numbers of Hispanic/LatinX, Black, and Asian individuals across the age range, representing high-risk and understudied populations; in turn, our health system is one of the nation’s highest volume centers for treating COVID-19 patients. Our specific aims are to: (1) identify distinct trajectories and determinants of susceptibility and immunity to SARS-CoV-2; and (2) identify distinct immune-inflammatory profiles (including bioactive lipid eicosanoids, acute phase proteins, cytokines, and their derivatives) associated with susceptibility and immunity to SARS-CoV-2. We will use both baseline measures and perform serial SARS-CoV-2 serologic measures (IgG + IgM) to longitudinally map serologic response with clinical and functional measures and define specific trajectories of susceptibility vs resistance (i.e. variations in degree of vulnerability to infection and illness, rate of recovery, and ability to maintain durable clinical immunity to re-infection or co-infection by other viral illnesses such as influenza). Lastly, we will examine heterogeneity in trajectories by sex, age, race/ethnicity, socioeconomic status, and host-environment modifiers (e.g. smoking, diet, and other lifestyle/behavioral factors). This CORALE-SeroNet Project 1 will identify the clinical and molecular profiles that signal robust immune reconstitution and functional recovery following SARS-CoV-2 exposure in multiple diverse populations including understudied minorities.

抽象的 施加问题与始终观察到的有关主机可变性质的悖论有关 敏感性和对SARS-COV-2的反应。我们和其他人报告了更积极的差异和更大的 老年人和种族/种族少数群体的发病率，尤其是某些合并症和代谢。 迄今为止，迄今为止的证据表明，尽管有些人表现出特殊的脆弱性 2（即敏感性），许多其他人具有对感染的内在或获得的相对免疫力（即抗性） 或疾病风险或出于未知原因。进一步加剧了SARS-COV-2风险的神秘性是 关于免疫措施的矛盾数据。我们和其他人发现个人的程度 展示感染后的IgG抗体对SARS-COV-2的反应是高度可变的 - 许多人没有 症状解决后的数周到几个月内，在周围循环中检测到的抗体。我们 假设：（H1）对SARS-COV-2暴露的反应自然历史标志着可辨认的模式 易感性与抗药性因人口，临床和宿主环境因素而异；和（H2） 分歧的临床轨迹是由复杂免疫中的个体间差异驱动的 对SARS-COV-2暴露的炎症反应。根据早期观察和新兴数据，我们预计 暴露的个体中的四个潜在临床轨迹：（i）暴露的人，但显然没有感染； （ii）感染最少至没有症状的感染，然后是持续的免疫组织化学； （ii）感染症状，恢复， 持续的免疫学；以及（iv）感染，恢复，重新感染。为了检验这些假设，我们建议利用 我们现有的珊瑚研究（n = 10,370），这是一项主要大都市的前瞻性纵向队列研究 南加州的医疗保健系统。我们的集水区包括大量西班牙裔/拉丁裔，黑色， 以及整个年龄范围内的亚洲人，代表高风险和知识的人群；反过来，我们的 卫生系统是全美治疗COVID-19患者的最高体积中心之一。我们的具体目标 为：（1）确定不同的轨迹并确定对SARS-COV-2的敏感性和免疫力； （2） 鉴定不同的免疫炎性特征（包括生物活性脂质类类，急性相蛋白， 细胞因子及其衍生物）与SARS-COV-2的敏感性和免疫力相关。我们将两者都使用 基线测量并执行串行SARS-COV-2血清学测量（IgG + IgM） 使用临床和功能措施的血清学反应，并定义了敏感性的特定轨迹 抗药性（即感染和疾病的脆弱程度，康复率和维持能力的变化 持久的临床免疫力可通过其他病毒疾病（例如影响力）再感染或共同感染）。最后，我们会的 通过性别，年龄，种族/种族，社会经济地位和宿主环境检查轨迹中的异质性 修饰符（例如吸烟，饮食和其他生活方式/行为因素）。这个Corale-Seronet项目1将确定 临床和分子特征，以稳健的免疫重建和功能恢复为信号 SARS-COV-2在包括知识少数群体在内的多个潜水员人群中的暴露。