Lead Exposure and Humoral Immunity to Varicella Zoster Virus in the United States: A Nationwide Cross-Sectional Study.

Varicella zoster virus (VZV) infection is typically mild in children but may result in severe complications in some cases. Environmental lead exposure is known to impair immune function; however, its relationship with VZV-specific humoral immunity has not been well characterized. We analyzed data from 7,938 participants aged 6-19 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 to examine the association between blood lead levels (BLL) and VZV IgG concentrations. Multivariable linear regression models were used to evaluate this association, and dose-response relationships were explored to assess potential nonlinearity. After adjustment for potential confounders, higher BLL was significantly associated with lower VZV IgG levels (β = -0.24, 95% CI: -0.43, -0.05, p = 0.013), with no evidence of effect modification by demographic or metabolic factors. A nonlinear dose-response relationship was identified, with a stronger inverse association observed below the inflection point of 1 μg/dL (β = -1.23, 95% CI: -2.22, -0.24) compared with levels above this threshold (β = -0.14, 95% CI: -0.35, 0.08); the log-likelihood ratio test confirmed significant nonlinearity (p = 0.045). These findings suggest that even low-level lead exposure may be associated with reduced VZV IgG concentrations among U.S. children and adolescents, highlighting potential immunological effects of environmental lead exposure.