Associations of serum PFAS with COVID-19 antibody levels among fully vaccinated adults

Per- and polyfluoroalkyl substances (PFAS) including PFOA, PFOS, and PFHxS have been observed to alter immune function. The most sensitive effect is suppressed antibody response following vaccination, particularly for tetanus and diphtheria in children. To assess whether this functional test also works in adults, we investigated associations of COVID-19 antibody levels among vaccinated adults with serum PFAS. This study included 74 participants who were fully vaccinated for COVID-19 within 1 to 6 months prior to the blood draw. We recruited participants from an existing cohort (n = 100) with PFAS-contaminated drinking water (1600 ng/L). Blood samples were collected between June and November 2021 and quantified for PFAS and SARS-CoV-2 IgG Spike antibody (IgG Spike). Associations of serum PFAS and IgG Spike were quantified using multiple linear regression adjusted for age, sex, BMI, vaccine type, and days since vaccination in models with and without seven participants with prior COVID-19. The nine PFAS detected in ≥70% of participant serum samples were summed as Σ9PFAS, which ranged from 0.93 to 311 μg/L and was predominant for PFOA, PFOS, and PFHxS. Concentrations of IgG Spike were significantly negatively associated with serum PFHxS (β = -0.38, p = 0.002), PFOS, PFHpS, and ∑9PFAS. When seven participants with prior COVID-19 were excluded from the analysis, associations were attenuated and non-significantly negative for PFHxS (β = -0.16, p = 0.10) PFOA, PFOS, PFHpS, and ∑9PFAS. In stratified analyses, negative associations were stronger among older, male, and overweight/obese subgroups. Overall, our findings are consistent with growing evidence of PFAS immunotoxicity across the lifespan and emphasize the importance of pathogen naivety when using vaccine antibody response in adults as a functional test of immunotoxicity.