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

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.