Age-related Imaging, Inflammatory, and Immune Phenotypes of Varicella Pneumonia Enabled by AI-derived CT Quantification

Background Varicella pneumonia is one of the major complications of varicella-zoster virus infection; however, age-related differences in imaging burden and inflammatory–immune responses remain insufficiently characterized. Artificial intelligence (AI) – driven Computed tomography (CT) quantification offers an objective approach for evaluating lesion burden and disease heterogeneity. Objectives This study aimed to characterize the age-specific imaging, inflammatory, and peripheral immune profiles of varicella pneumonia using AI-derived CT quantitative biomarkers—the Nodular Load Index (NLI) and whole-lung infection ratio—and to explore their potential roles in risk stratification and clinical management. Methods In this dual-center retrospective study, 104 patients with varicella pneumonia were categorized into children (< 10 years, n = 28), adolescents (10–19 years, n = 41), and adults (> 19 years, n = 35). An AI-CT pipeline automatically extracted nodule counts, total nodule volume, and mean nodule attenuation; these were standardized and summed to construct the NLI. Whole-lung infection ratio was quantified simultaneously. Clinical variables, laboratory parameters, and CT-derived metrics were compared across age groups. Spearman correlation assessed associations between imaging biomarkers and systemic inflammatory and peripheral T-cell immune indicators. Results Adults exhibited significantly higher NLI and C-reactive protein (CRP) levels than children and adolescents (all P < 0.05), indicating greater nodular inflammatory burden and systemic inflammation. Children showed higher white blood cell counts (WBC) and absolute CD4⁺ T-cell numbers compared with adults (P < 0.05), reflecting more active peripheral immune responses. NLI was negatively correlated with neutrophil percentage, procalcitonin, and CD4⁺/CD8⁺ T-cell ratio, but positively correlated with lymphocyte percentage and the proportion of CD8⁺ T cells among CD3⁺ T cells (all P < 0.05). No significant associations were observed between whole-lung infection ratio and inflammatory or immune parameters. Conclusions Varicella pneumonia demonstrates marked age-related heterogeneity in imaging, systemic inflammation, and peripheral immune responses. Adults present with higher NLI and CRP, whereas children show more active peripheral immune responses. AI-derived NLI accurately quantifies hematogenously disseminated “nodule-plus-halo” lesions and correlates with peripheral immune status, providing a promising biomarker for disease stratification and clinical management. Prospective studies are warranted to validate its robustness and prognostic value.