Per- and Polyfluoroalkyl Substances (PFAS) Exposures and COVID-19 Vaccine Effectiveness

项目摘要/摘要 年感染SARS-CoV-2及其相关疾病新冠肺炎已导致超过374,000人死亡 到目前为止，美国。预防新冠肺炎的疫苗最近得到了食品和药物管理局的紧急使用 并正在向高风险个人进行管理，随后将进行更广泛的传播。暴露于 每种或多种氟烷基物质(PFAS)与疫苗接种后免疫反应降低有关 抗其他感染，但其对新冠肺炎疫苗效力的影响尚不清楚。我们有一个时间敏感的 有机会确定血清全氟辛烷磺酸对新冠肺炎疫苗接种反应的影响，建立在独特的 对亚利桑那州约2,000名医护人员、急救人员和其他基本工作人员进行的研究-之前没有COVID- 19人感染，其中许多人最近接种了疫苗，或将在未来几个月接种疫苗， 亚利桑那州和佛罗里达州的一项类似研究增加了约700名参与者。我们的目标是 本应用旨在确定全氟辛烷磺酸暴露水平对新冠肺炎疫苗效力的影响。我们的 中心假设是，增加PFAS血清浓度将：1)降低最初的SARS-CoV-2抗体 新冠肺炎接种后的滴度；2)增加抗体滴度的纵向下降率；和3) 在接种疫苗后的九个月内增加新冠肺炎的使用频率。这样做的理由是 研究表明，成功的完成有望为全氟辛烷磺酸的免疫效果提供新的数据。 曝光。我们将通过两个常规的和一个探索性的具体目标来检验这些假设：1)评估 新冠肺炎接种后血清PFAS与SARS-CoV-2初始抗体滴度的相关性2)评价 新冠肺炎后血清卵泡刺激素与SARS-CoV-2抗体滴度纵向下降的关系 以及3)评估血清PFAS浓度与新冠肺炎发病频率的关系 在接种疫苗后。对于目标1和目标2，我们将从亚利桑那州的研究参与者中选择600人进行测量 新冠肺炎接种后的血清PFAS。作为研究的一部分，这些参与者还将为 每三个月检测一次SARS-CoV-2抗体，至少九个月，并为呼吸道提供 每周采集样本进行聚合酶链式反应检测，以确定SARS-CoV-2感染情况。出于探索的目的，我们将确定所有 亚利桑那州和佛罗里达州研究人群接种疫苗后的新冠肺炎病例，以及每个病例 选择接种新冠肺炎疫苗但未感染SARS-CoV-2的5名匹配对照。血清 将对病例和对照的全氟辛烷磺酸水平进行比较。在研究完成时，我们将记录 接触PFAS对新冠肺炎疫苗接种后SARS-CoV-2抗体及感染频率的影响 接种疫苗后出现新冠肺炎病例。考虑到PFAS的潜力，拟议的研究具有重要意义 暴露会降低新冠肺炎疫苗的有效性。这项拟议的研究具有创新性，因为它是 据我们所知，首先确定血清PFAS水平与新冠肺炎指标之间的关系 疫苗的有效性。

PROJECT SUMMARY/ABSTRACT Infection with SARS-CoV-2 and its associated disease state, COVID-19, has resulted in over 374,000 deaths in the United States to date. Vaccines protecting against COVID-19 have recently received FDA emergency use authorization and are being administered to high-risk individuals with wider dissemination to follow. Exposure to per- or polyfluoroalkyl substances (PFAS) is associated with reduced immune response following vaccination against other infections, but its effect on COVID-19 vaccine effectiveness is not known. We have a time-sensitive opportunity to determine the effect of serum PFAS on response to COVID-19 vaccination, building on a unique study in ~2,000 healthcare workers, first responders and other essential workers in Arizona without prior COVID- 19 infection, many of whom have either recently been vaccinated or will be vaccinated in the coming months, supplemented by ~700 additional participants from a similar study in both Arizona and Florida. Our objective in this application is to determine the effects of PFAS exposure levels on COVID-19 vaccine effectiveness. Our central hypotheses are that increased PFAS serum concentrations will: 1) reduce initial SARS-CoV-2 antibody titers following COVID-19 vaccination; 2) increase the rate of longitudinal decline in antibody titers; and 3) increase the frequency of COVID-19 during a nine-month period following vaccination. The rationale for this research is that successful completion can be expected to provide new data about the immune effects of PFAS exposure. We will test these hypotheses through two regular and one exploratory specific aims: 1) Evaluate the association of serum PFAS with initial SARS-CoV-2 antibody titers following COVID-19 vaccination; 2) Evaluate the association of serum PFAS with longitudinal decline in SARS-CoV-2 antibody titers following COVID-19 vaccination; and 3) Evaluate the association of serum PFAS concentrations with frequency of COVID-19 following vaccination. For aims 1 and 2, we will select 600 of our Arizona study participants for measurement of serum PFAS following COVID-19 vaccination. As part of the study, these participants will also provide serum for measurement of SARS-CoV-2 antibodies every three months for at least nine months, and provide respiratory samples weekly for PCR testing to identify SARS-CoV-2 infection. For the exploratory aim, we will identify all COVID-19 cases following vaccination in both the Arizona and Florida study populations, and for each case select five matched controls who received COVID-19 vaccination but were not infected with SARS-CoV-2. Serum PFAS levels will be compared across the cases and controls. At study completion, we will have documented the effects of PFAS exposure on SARS-CoV-2 antibodies following COVID-19 vaccination and the frequency of COVID-19 cases following vaccination. The proposed research is significant given the potential for PFAS exposure to reduce the effectiveness of COVID-19 vaccines. The proposed research is innovative as it is the first to our knowledge to determine the association between serum PFAS levels and measures of COVID-19 vaccine effectiveness.