COVID-19 Administrative Supplement for FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III

针对 FOXO3 基因型、炎症老化、心血管疾病和痴呆的 COVID-19 行政补充。

• 批准号: 10170094
• 负责人: BRADLEY JOHN WILLCOX
• 金额: $ 46.07万
• 依托单位: KUAKINI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170094
• 关键词: 2019-nCoV; Address; Administrative Supplement; Age; Anti-Inflammatory Agents; Antibodies; Asian Americans; Authorization documentation; COVID-19; Cardiovascular Diseases; Cardiovascular system; Case Fatality Rates; Cohort Studies; Communities; Coronavirus; Data; Dementia; Elderly; Emergency Situation; Epidemiology; FOXO3A gene; Female; Genetic; Genotype; Germany; Goals; Habits; Hawaii; Health; Heart; Herd Immunity; Hospitalization; Infection; Inflammaging; Japanese American; Japanese Population; Letters; Longevity; Lung; Measures; Medical Device; Medical History; Morbidity - disease rate; Older Population; Outcome; Participant; Persons; Population; Prevalence; Prevalence Study; Public Health; Questionnaires; Recording of previous events; Reporting; Risk; Risk stratification; Sampling; Sampling Studies; Sensitivity and Specificity; Severities; Severity of illness; Social Distance; Specificity; Symptoms; Testing; Underrepresented Populations; United States; Universities; Virus; Virus Diseases; aged; base; comorbidity; experience; infection rate; insight; interest; male; mental state; middle age; minority communities; offspring; programs; protective allele; recruit

Abstract The SARS-CoV-2 virus that causes COVID-19 infection is among the most serious public health challenges in the last century. However, the true prevalence of COVID-19 infection in the Hawaii community is unknown-- we do not know how widespread undiagnosed infections are, true morbidity levels, true case-fatality rates, nor whether herd immunity exists in some populations. This information may help facilitate easing of social distancing measures among other important epidemiological issues. Data from Johns Hopkins University suggest that Hawaii has one of the lowest COVID-19 infection rates in the United States (U.S.) with only 36 confirmed coronavirus cases per 100,000 persons (as of mid-April 2020). This was much lower than the U.S. national rate of 177 infections per 100,000 persons – both of which are hypothesized to be vastly underestimated, primarily due to high numbers of undiagnosed infections. One approach to help resolve these challenges is to test populations for COVID-19 antibodies (Ab). Early results from such studies in the U.S. mainland, Germany, and Holland, have found that 2% to 30% of populations have previously been infected with this coronavirus. We propose to help address these issues by sampling an underrepresented population of older Asian- Americans in Hawaii that have been well studied for other outcomes of interest (e.g. health habits, comorbidities, genetics, etc.) using a reliable Ab test that has FDA emergency use authorization (EUA) and the highest sensitivity and specificity. We propose the following Specific Aims: Primary Aim: Test the hypothesis that the prevalence rate of prior COVID-19 infection in middle-aged and elderly persons in the Japanese-American community in Hawaii will be higher than reported prevalence rates. Since the majority of persons in Hawaii tested for COVID-19 infections thus far have been symptomatic persons, we hypothesize that the actual prevalence rates of prior virus infection within this community are much higher than official reports from the Hawaii Department of Health (Hawaii Department of Health est. 36 cases per 100,000 persons in mid-April 2020). Our study sample will be drawn from a stratified random sample of over 2,000 previously recruited Kuakini Honolulu Heart Program Offspring Study (Kuakini HHP Offspring Study) participants (n=1,200; age range = 50-90 years). Exploratory Aim #1: Test the hypothesis that those with SARS-CoV-2 Ab+ (positive) tests, and who possess the longevity-associated FOXO3 and ACE-2 (anti-inflammatory) genotypes, will have experienced less severe COVID-19 related-illness (e.g. fewer overall symptoms, fewer pulmonary/cardiovascular symptoms, fewer hospitalizations, shorter duration of illness, etc.) than those with the common genotype. These study participants will be drawn from the Kuakini HHP Offspring Study cohort who test Ab positive (est. at 2%-30% of sample, i.e. 32-480 persons). Ab+ participants will be asked to complete a questionnaire detailing severity of symptoms and stratified by FOXO3 genotype. Exploratory Aim #2: Test the hypothesis that the longevity associated FOXO3 genotype and protective ACE-2 genotype will correlate with lower risk for COVID-19 infection i.e. fewer FOXO3/ACE-2 protective allele carriers will test positive for SARS-CoV-2 Ab. We hypothesize that those with the FOXO3/ACE-2 longevity-associated genotypes will be protected from COVID-19 infection.

抽象的 引起Covid-19感染的SARS-COV-2病毒是最严重的公共卫生挑战之一 上个世纪。但是，夏威夷社区中共vid-19感染的真正流行尚不清楚 - 我们 不知道未经诊断的未诊断感染是多么普遍，真实的发病率水平，真实病例率率，也不 某些人群中是否存在畜群的免疫力。这些信息可能有助于促进社会的放松 疏远措施以及其他重要的流行病学问题。约翰·霍普金斯大学的数据 建议夏威夷是美国（美国）的Covid-19感染率最低的，只有36 确认每10万人（截至2020年中期）确认冠状病毒病例。这比美国低得多 全国率为每10万人的177种感染 - 两个人都被认为是巨大的 被低估的主要是由于未诊断未诊断的感染数量高。一种帮助解决这些的方法 挑战是测试与19个抗体（AB）的种群。美国此类研究的早期结果 大陆，德国和荷兰发现，以前有2％至30％的人口被感染 与此冠状病毒。 我们建议通过抽样代表性不足的亚洲年龄较大的人口来帮助解决这些问题。 夏威夷的美国人已经为其他感兴趣的结果进行了很好的研究（例如，健康习惯， 合并症，遗传学等）使用具有FDA紧急使用授权（EUA）的可靠AB测试和 最高灵敏度和特异性。 我们提出以下具体目标： 主要目的：检验以下假设： 夏威夷日裔美国人社区的老年人将高于报道 患病率。由于夏威夷的大多数人迄今已测试了COVID-19的感染 有症状的人，我们假设此处先前病毒感染的实际患病率 社区要比夏威夷卫生部（夏威夷夏威夷部门的官方报告都要高得多 卫生估计36例，每10万人2020年中期）。我们的研究样本将从分层 2,000多个先前招募的Kuakini檀香山心脏计划后代研究（Kuakini）的随机样本 HHP后代研究）参与者（n = 1,200；年龄范围= 50-90岁）。 探索性目的＃1：检验以下假设：SARS-COV-2 AB+（阳性）测试以及谁 拥有寿命相关的FOXO3和ACE-2（抗炎）基因型，将具有 经历了不太严重的Covid-19相关性（例如，总体症状较少，较少 肺/心血管符号，住院率较少，病情较短等） 具有共同基因型的人。这些研究参与者将从kuakini HHP后代中汲取灵感 研究队列的研究队员阳性测试（占样本的2％-30％，即32-480人）。 AB+参与者将 被要求填写一份调查表，详细介绍了符号的严重性，并由FOXO3基因型分层。 探索目的＃2：检验寿命相关的FOXO3基因型和受保护的假设 ACE-2基因型将与COVID-19感染的风险较低，即受保护的FOXO3/ACE-2更少 等位基因载体将测试SARS-COV-2 AB的阳性。我们假设那些具有FOXO3/ACE-2的人 寿命相关的基因型将受到远免受COVID-19的感染的保护。