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

项目概要/摘要 感染SARS-CoV-2及其相关疾病COVID-19已导致超过374，000人死亡， 美国至今。预防COVID-19的疫苗最近获得了FDA的紧急使用 授权，并正在管理高风险的个人，更广泛的传播，以遵循。暴露于 全氟或多氟烷基物质（PFAS）与接种疫苗后免疫应答降低有关 抗其他感染，但其对COVID-19疫苗有效性的影响尚不清楚。我们有一个时间敏感的 有机会确定血清PFAS对COVID-19疫苗接种反应的影响， 在亚利桑那州约2，000名医疗保健工作者，第一反应者和其他基本工作人员中进行的研究，这些工作人员没有先前的COVID- 19例感染，其中许多人最近接种了疫苗或将在未来几个月接种疫苗， 由来自亚利桑那州和佛罗里达的类似研究的约700名额外参与者补充。我们的目标是 本申请旨在确定PFAS暴露水平对COVID-19疫苗有效性的影响。我们 中心假设是，增加PFAS血清浓度将：1）降低初始SARS-CoV-2抗体 COVID-19疫苗接种后的滴度; 2）增加抗体滴度的纵向下降率;以及3） 在接种疫苗后的9个月内增加COVID-19的发病频率。这样做的理由 这项研究的成功完成有望为PFAS的免疫效果提供新的数据 exposure.我们将通过两个常规和一个探索性的具体目标来测试这些假设：1）评估 血清PFAS与COVID-19疫苗接种后初始SARS-CoV-2抗体滴度的相关性; 2）评估 血清PFAS与COVID-19后SARS-CoV-2抗体滴度纵向下降的相关性 疫苗接种;以及3）评估血清PFAS浓度与COVID-19频率的相关性 接种疫苗后。对于目标1和2，我们将选择600名亚利桑那州的研究参与者， 接种COVID-19疫苗后血清PFAS。作为研究的一部分，这些参与者还将提供血清 每三个月测量一次SARS-CoV-2抗体，持续至少九个月，并提供呼吸道 每周抽取样本进行PCR检测，以确定是否感染SARS-CoV-2。为了探索性的目的，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COVID-19病例，以及每例病例 选择5名接受COVID-19疫苗接种但未感染SARS-CoV-2的匹配对照。血清 将比较病例和对照组的PFAS水平。研究完成时，我们将记录 PFAS暴露对COVID-19疫苗接种后SARS-CoV-2抗体的影响以及 接种疫苗后的COVID-19病例。鉴于PFAS的潜力，拟议的研究具有重要意义 暴露，以降低COVID-19疫苗的有效性。这项研究是创新的，因为它是 据我们所知，这是第一次确定血清PFAS水平与COVID-19指标之间的关联 疫苗有效性。

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.