High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy
PFAS (Per- and Polyfluoroalkyl Substances), often called “forever chemicals,” are industrial chemicals widely used due to their durability. Their extensive use and tendency to bioaccumulate have raised significant public health concerns. In particular, PFAS exposure has been associated with weakened immune responses after vaccination, including reduced immunosuppression biomarkers such as immunoglobulin production. Studies have highlighted the connection between PFAS exposure during pregnancy and immune response in both mothers and children. For example, the Norwegian Mother and Child Cohort Study reported significant inverse associations between the concentrations of maternal blood perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) measured at delivery, and the levels of anti-rubella antibodies in the children’s sera at age three years. Given PFAS’s known influence on immune function, recent studies have begun exploring how PFAS exposure may impact immune responses to specific infections, including SARS-CoV-2. Indeed, communities exposed to higher levels of PFAS exhibited higher odds of COVID-19 mortality (Catelan et al., 2021). Moreover, elevated plasma levels of perfluorobutanoic acid (PFBA) are associated with more severe SARS-CoV-2 infections, while higher serum levels of PFOS, PFHxS, and PFNA are linked to a weaker antibody response after SARS-CoV-2 infection. Our team previously found that levels of a mixture of PFAS, including linear- (n-)PFOA, PFHxS, perfluoroheptanesulfonic acid (PFHpS), and perfluorohexanoic acid (PFHxA), were inversely associated with maternal SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. However, the underlying biological mechanisms are not yet fully understood.
