Per- and Polyfluoroalkyl substances (PFAS) Exposures and COVID-19 in Firefighters

项目总结/摘要 SARS-CoV-2感染及其相关疾病COVID-19的传播导致了全球大流行。 暴露于全氟或多氟烷基物质（PFAS）与免疫反应降低有关，但其 对COVID-19的影响尚不清楚。我们有一个时间敏感的机会来确定血清PFAS的效果 在全州范围内开展了一项独特的SARS-CoV-2抗体消防员测试计划。我们长久以来- 长期目标是确定PFAS混合物的健康风险。我们在此应用中的目的是评估 消防员的PFAS暴露水平与COVID-19感染的严重程度和免疫反应有关。 我们的假设是，PFAS血清浓度增加将增加COVID-19感染的严重程度 并降低恢复后的血清学滴度，从而增加以后再次感染的风险。我们将测试 这些假设通过两个特定的目的：1）确定血清PFAS浓度与 感染严重程度; 2）确定血清PFAS与SARS-CoV-2抗体滴度的相关性。为宗旨 1，从我们的州登记处招募，我们将招募100名图森和凤凰城消防员与积极的SARS-CoV- 2 IgM和/或IgG抗体，并收集和分析其血清用于PFAS。使用在线调查工具 在生物样本采集时完成，我们将获得关于受试者是否 经诊断检测确诊的COVID-19感染，症状程度（如有）与COVID-19一致 感染，以及是否住院。我们将评估血清PFAS与以下因素之间的关系：1） 症状严重程度; 2）有症状与无症状COVID-19感染; 3）住院治疗。对于目标2， 我们将在5个月和10个月后对所有参加研究的消防员重复SARS-CoV-2 IgG检测 以测量免疫应答的变化，并测试PFAS水平与纵向变化的相关性， 在IgG中使用广义线性回归模型解释重复测量。研究完成时，我们 将记录PFAS暴露对有症状的COVID-19感染可能性的影响， 高度暴露人群的症状严重程度，以及PFAS暴露对随后的 免疫反应持久性。考虑到PFAS暴露于 增加COVID-19已经严重的健康后果的风险，并减少长期免疫 反应拟议的研究是创新的，因为它是第一次我们的知识，以确定协会 血清PFAS水平和COVID-19之间的联系

PROJECT SUMMARY/ABSTRACT The spread of SARS-CoV-2 infection and its associated disease state, COVID-19, has led to a global pandemic. Exposure to per- or polyfluoroalkyl substances (PFAS) is associated with reduced immune response, but its effect on COVID-19 is not known. We have a time-sensitive opportunity to determine the effect of serum PFAS on COVID-19, building on a unique statewide firefighter testing program for SARS-CoV-2 antibodies. Our long- term goal is to identify health risks of PFAS mixtures. Our objective in this application is to evaluate the effects of PFAS exposure levels in firefighters in regards to the severity of and immune response to COVID-19 infection. Our hypotheses are that increased PFAS serum concentrations will increase the severity of COVID-19 infection and reduce post-recovery serologic titers, which could thereby increase risk of later re-infection. We will test these hypotheses through two specific aims: 1) Determine the association of serum PFAS concentrations with infection severity; and 2) Determine the association of serum PFAS with SARS-CoV-2 antibody titers. For aim 1, recruiting from our state registry, we will enroll 100 Tucson and Phoenix firefighters with positive SARS-CoV- 2 IgM and/or IgG antibodies, and collect and analyze their serum for PFAS. Using an online survey instrument completed at the time of biological sample collection, we will obtain information on whether the subjects had COVID-19 infection(s) confirmed by diagnostic testing, extent of symptoms (if any) consistent with COVID-19 infection, and whether they were hospitalized. We will evaluate the association between serum PFAS and: 1) severity of symptoms; 2) symptomatic vs. asymptomatic COVID-19 infection; and 3) hospitalization. For aim 2, we will repeat SARS-CoV-2 IgG testing after five months and ten months in all firefighters enrolled in the study to measure changes in immune response and to test the association of PFAS levels and longitudinal changes in IgG using generalized linear regression models that account for repeated measures. At study completion, we will have documented the effects of PFAS exposure on the likelihood of a symptomatic COVID-19 infection and symptom severity in a highly exposed population, as well as effects of PFAS exposure on the subsequent immune response persistence. The proposed research is significant given the potential for PFAS exposure to increase the risk of already severe health consequences of COVID-19 and to reduce long-term immune response. The proposed research is innovative as it is the first to our knowledge to determine the association between serum PFAS levels and COVID-19.