Project 1: COVID-19 prevalence, transmission, and protection in extended first responder cohorts

项目1总结 新冠肺炎的迅速传播及其极端的病理范围使人们迫切需要了解 SARS-CoV-2感染后的传播和保护水平。这些问题是最有效的 与接触风险较高的个人以及他们最频繁的接触者进行队列研究。项目1 将在这样一个群体中回答有关新冠肺炎传播和保护的紧迫问题，哥伦布，俄亥俄州 急救人员及其家庭接触者。将进行纵向血清学和病毒检测 项目1团队在未来五年内确定新冠肺炎的流行率、传播和保护 这群人。研究计划的一个固有特征是它的灵活性，也允许我们以血清学/病毒为中心 追踪疫苗何时可用，很可能会在第一阶段部署到这一高风险队列。 我们将采用我们机构开发或验证的一组血清学和遗传分析方法，以 解决有关新冠肺炎的主要知识差距，包括：(1)高危暴露人群中的流行率；(2) 与个人防护措施的因果关系，(3)家庭接触者之间的传播，(3)病毒载量和 PCR阳性结果是否等同于传染性病毒；(Iv)抗体应答的进化和持久性 自然感染和再感染的一系列症状，(V)接种疫苗后的体液免疫反应 (6)预防接种疫苗后再次感染或感染。 重要的是，项目1研究将受益于OSU为我们提议的临床项目提供资金的承诺 测试。该项目还将受益于急诊医学跨学科专家的整合， 免疫学、病毒学、病理学、传染病、流行病学、生物统计学和生物伦理学 与地方/州机构建立伙伴关系。项目1将通过两个目标完成。目标1.增强现有的 基础设施对一批急救人员、工作人员和家庭接触者进行纵向抽样。我们有 为哥伦布地区这一高风险暴露群体的参与建立了高买入率 (预计招聘下限为约2,500人)。目的2.测定抗体的持续期和保护性 STOP-COVID参与者的反应。我们希望征集广泛的参与者，他们在 研究将包括幼稚的、先前接触过的、无症状的和有症状的个体。我们将利用 纵向血清学数据，以跟踪所有类别的暴露个人的规模，持续时间， 中和能力和抗体反应的保护性。当疫苗可用时，参与者将 提供密切跟踪的优先接受者队列，以监测对疫苗的体液免疫反应 幼稚和以前接触过的人再次接触的风险很高。这些研究将与以下方面产生协同作用： 项目2，深入描述免疫反应和病毒株，核心B为基础 抗体和病毒检测，核心C用于项目设计、流行病学和生物统计，并将提供数据 至项目3，用于与不同群体交流测试结果及其影响。

PROJECT 1 SUMMARY The rapid spread COVID-19 and its extreme range of pathologies creates an urgent need to understand transmission and levels of protection following SARS-CoV-2 infection. These issues are most effectively studied in cohorts with individuals at high risk of exposure and, critically, their most frequent contacts. Project 1 will answer pressing questions about COVID-19 transmission and protection in such a group, Columbus, OH first responders and their household contacts. Longitudinal serology and virus testing will be performed over the next five years by the Project 1 team to determine COVID-19 prevalence, transmission, and protection in this cohort. An inherent feature of the research plan is its flexibility, also allowing us to pivot serological/viral tracking when vaccines are available, which, likely, will be deployed in a first stage to this high-risk cohort. We will employ a panel of serological and genetic assays, developed or validated at our institution, to address key knowledge gaps about COVID-19, including: (i) prevalence among a high-risk exposure group, (ii) causal relationships with PPE practices, (iii) transmission among household contacts, (iii) viral load and whether positive PCR results equate with infectious virus, (iv) evolution and durability of Ab responses to natural infection and re-infection over a range of symptoms, (v) humoral immune responses post-vaccination in naïve and previously infected individuals, and (vi) protection from re-infection or infection post-vaccination. Importantly, Project 1 studies will benefit from an OSU commitment to fund our proposed clinical testing. The project also will benefit from integration of transdisciplinary experts from emergency medicine, immunology, virology, pathology, infectious disease, epidemiology, biostatistics, and bioethics, as well as partnerships with local/state agencies. Project 1 will be accomplished in two Aims. AIM 1. Enhance existing infrastructure to longitudinally sample a cohort of first responders, staff, and household contacts. We have established a high buy-in rate for participation of this high-exposure risk group in the Columbus area (anticipated lower limit recruitment of ~2,500). AIM 2. Determine duration and protectiveness of antibody responses in STOP-COVID participants. We expect to enlist a broad spectrum of participants who, during the study, will include naïve, previously exposed, asymptomatic, and symptomatic individuals. We will leverage longitudinal serologic data to track all categories of exposed individuals for the magnitude, duration, neutralizing capacity, and protectiveness of antibody responses. When a vaccine is available, participants will provide a closely tracked cohort of priority recipients to monitor humoral immune responses to the vaccine in naïve and previously exposed individuals at a high risk for re-exposure. These studies will synergize with: Project 2 for an in-depth characterization of the immune responses and virus strains, with Core B for basic antibody and virus testing, with Core C for project design, epidemiology, and biostatistics, and will provide data to Project 3 for communication of test results and their implications with diverse groups.