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.