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

摘要 导致COVID-19感染的SARS-CoV-2病毒是美国最严重的公共卫生挑战之一， 上个世纪。然而，夏威夷社区的COVID-19感染的真实流行率尚不清楚--我们 不知道未确诊的感染有多普遍，真实的发病率水平，真实的病死率，也不知道 群体免疫是否存在于某些人群中这些信息可能有助于缓解社会 在其他重要的流行病学问题中采取距离措施。数据来自约翰霍普金斯大学 表明夏威夷是美国COVID-19感染率最低的地区之一只有36 每10万人的冠状病毒确诊病例数（截至2020年4月中旬）。这远远低于美国。 全国感染率为每10万人177例-这两种情况都被假设为 这主要是由于大量未确诊的感染。一种帮助解决这些问题的方法 挑战是测试人群的COVID-19抗体（Ab）。美国此类研究的早期结果显示， 大陆、德国和荷兰发现，2%到30%的人口以前曾被感染过 这种冠状病毒。 我们建议通过对代表性不足的亚洲老年人进行抽样调查来帮助解决这些问题- 在夏威夷的美国人已经被很好地研究了其他感兴趣的结果（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）和 最高的灵敏度和特异性。 我们提出以下具体目标： 主要目的：检验中年人既往COVID-19感染的患病率 在夏威夷的日裔美国人社区， 流行率。由于迄今为止夏威夷接受COVID-19感染检测的大多数人都是 有症状的人，我们假设，在这一范围内， 社区远远高于官方报告从夏威夷卫生部（夏威夷部 健康测试2020年4月中旬每10万人36例）。我们的研究样本将从分层的 随机抽取2,000多名以前招募的Kuakini檀香山心脏计划后代研究（Kuakini HHP后代研究）参与者（n= 1，200;年龄范围= 50-90岁）。 探索性目标#1：检验SARS-CoV-2 Ab+（阳性）检测的假设， 拥有长寿相关的FOXO 3和ACE-2（抗炎）基因型， 经历了不太严重的COVID-19相关疾病（例如，总体症状较少， 肺/心血管症状，住院次数减少，病程缩短等）比 那些有共同基因型的人这些研究受试者将从Kuakini HHP后代中抽取 检测Ab阳性的研究队列（est.样本的2%-30%，即32-480人）。AB+参与者将 要求完成一份问卷，详细说明症状的严重程度，并按FOXO 3基因型分层。 探索性目标#2：检验长寿相关的FOXO 3基因型和保护性基因型的假设。 ACE-2基因型将与COVID-19感染风险降低相关，即FOXO 3/ACE-2保护性更低 等位基因携带者的SARS-CoV-2抗体检测呈阳性。我们假设那些FOXO 3/ACE-2 长寿相关基因型将受到保护，免受COVID-19感染。

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.