Serum Metabolic Profiling of Patients With Acute Herpes Zoster

Herpes zoster (HZ), caused by varicella-zoster virus reactivation, is characterized by painful dermatomal eruptions. Systemic metabolic alterations during acute infection remain incompletely defined. In this exploratory case-control study, serum samples from 47 acute HZ patients and 30 healthy controls were analyzed using untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Differential metabolic features were identified using models adjusted for age and analytical batch (p < 0.05; FC ≥ 1.2 or ≤ 0.83). Pathway enrichment was explored by over-representation analysis. A nested cross-validated LASSO-logistic regression model incorporating selected metabolites, age, and batch was constructed to assess exploratory internal discrimination. Thirty-eight differential metabolic features were identified, involving nucleoside, amino acid, lipid, and energy metabolism. Pyrimidine-related and amino acid-related pathways appeared among the leading nominal pathways. A four-metabolite panel (Uridine/Pseudouridine, Uracil, 2-Pyrrolidinone, and _L-Methionine), combined with age and batch, yielded an internal cross-validated AUC of 0.91 (95% CI: 0.8369-0.9688). These four core metabolic features retained the same directions of change in the age-overlap sensitivity cohort, with nucleoside-related features elevated and _L-Methionine decreased in HZ patients. Acute HZ is associated with alterations in serum metabolic features, particularly involving nucleoside-related and amino acid-related signals. These exploratory findings provide a metabolic overview of acute HZ and require validation in independent, age-matched cohorts.