Cytomegalovirus Infection in Population Samples: Are Whole-Blood Levels of Cadmium, Mercury, Selenium, and Manganese Associated with CMV Serostatus?

Abstract

Past experimental evidence links heavy metal exposure with immune function, but population-level associations with chronic viral infections remain unclear. We analyzed data on 554 U.S. participants (72% CMV-seropositive) to evaluate whether whole-blood levels of four metal, cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn), were associated with cytomegalovirus (CMV) serostatus. We fit unadjusted logistic regression models for each metal, conducted a Weighted Quantile Sum (WQS) mixture analysis, performed a mediation assessment for systemic inflammation (high-sensitivity C-reactive protein, hs-CRP), and ran sensitivity analyses (trimming outliers, excluding participants with hs-CRP >10 mg/L, and arranging by hs-CRP levels). The four blood metals had minimal inter-correlation (|ρ| ≤ 0.07). In unadjusted models, higher concentrations of Cd, Hg, and Mn were associated with lower odds of CMV seropositivity (odds ratios [ORs] < 1), whereas Se showed a positive but non-significant association (OR > 1). After excluding individuals with hs-CRP >10 mg/L (n=538), the inverse associations strengthened for Cd (OR ~0.63, 95% confidence interval [CI] 0.45–0.90), Hg (~0.68, 95% CI 0.53–0.88), and Mn (~0.49, 95% CI 0.27–0.91), while Se remained null (OR ~1.20, 95% CI 0.24–6.03). WQS mixture analysis identified Se as the top contributor (~77% weight) to the overall metal mixture effect, followed by Mn (~16%). Mediation by hs-CRP was negligible. In this exploratory, unadjusted analysis, higher blood levels of Cd, Hg, and Mn were less likely to be CMV-positive, but this might be due to other factors not accounted for. More research is needed using better-adjusted models before drawing firm conclusions.