Antibody response to SARS-CoV-2 mRNA vaccination in Danish adults exposed to perfluoroalkyl substances (PFASs): The ENFORCE study.

Introduction: Per- and polyfluoroalkyl substances (PFASs) have immunotoxic effects in children while studies in adults, including recent studies on the SARS-CoV-2 vaccine response have been less consistent. In a cohort of 50-69-year-olds repeatedly vaccinated against COVID-19 in Denmark from early 2021, we aimed to assess the association between serum-PFAS concentrations and SARS-CoV-2 antibody responses.

Methods: We assessed serum-PFAS concentrations among 371 middle-aged adults from the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE) who had received their first vaccination against COVID-19. Following the second dose and the booster (third) Pfizer-BioNTech mRNA vaccination, we measured the specific spike IgG antibody response. Associations between serum-PFAS concentrations at inclusion and spike IgG antibody concentrations after vaccination were assessed using median regression, and analyses were adjusted for age, sex, presence of diabetes, number of vaccines received, and time since vaccination. We further examined the associations between serum-PFAS concentrations at inclusion and changes in spike IgG antibody concentration between the second dose and booster (third) vaccination.

Results: Serum-PFAS concentrations were not associated with spike IgG antibody concentrations after the SARS-CoV-2 vaccinations, but the increase in response after the booster (third) vaccination compared to after the second vaccination was consistently lower at higher serum-PFAS concentrations. Each doubling in the concentration of seven serum-PFASs was associated with a 802 BAU/mL lower median increase in spike IgG antibody response after the booster (third) vaccination (95% CI: -1812; 208) adjusted for confounders.

Discussion: As many adults were probably not immunological naïve prior to vaccination, our results were likely affected by individual variability in immune response to the vaccination. Despite this uncertainty, the diminished increase in SARS-CoV-2 spike antibody response after the booster (third) vaccination at higher PFAS exposure may potentially reflect an immunotoxic impact of the PFASs.