Albumin-to-alkaline phosphatase ratio as an immuno-metabolic marker of bacterial co-infection phenotype in pediatric RSV infection: insights from protein–protein interaction networks

Respiratory syncytial virus (RSV) infection in children is frequently complicated by bacterial co-infection, which significantly aggravates clinical outcomes. The Albumin-to-Alkaline Phosphatase Ratio (AAPR) has recently emerged as a novel immuno-metabolic marker. This study aimed to investigate the association between AAPR and Gram-positive (G + ) versus Gram-negative (G-) bacterial co-infection phenotypes among RSV-infected children, evaluate its discriminative performance, and explore potentially relevant biological pathways. We retrospectively analyzed 153 pediatric patients with laboratory-confirmed RSV and bacterial co-infection. Multivariable logistic regression and restricted cubic spline (RCS) analyses were employed to determine the independent association and dose-response relationship between AAPR and infection phenotypes. Diagnostic performance was quantified using the area under the receiver operating characteristic curve (AUC). Additionally, an exploratory systems biology analysis was performed to identify candidate genes and signaling pathways potentially relevant to the observed association. Multivariable logistic regression demonstrated that elevated AAPR was independently and inversely associated with the likelihood of G+ infection (OR = 0.37; 95% CI: 0.15–0.89 for the highest vs. lowest tertile). RCS analysis showed no evidence of a nonlinear association ( P for non-linearity = 0.456). The association remained similar after nonlinear adjustment for age and was directionally consistent across age strata; however, it was attenuated after normalization using age-specific pediatric ALP reference limits. AAPR alone showed modest discriminative performance (AUC = 0.599). Addition of AAPR to CRP, WBC, and NEU increased the AUC from 0.455 to 0.613; however, the difference did not reach the conventional threshold for statistical significance ( P = 0.051). Exploratory systems biology analysis identified IL-17-, TNF-, and other inflammation-related pathways as candidates for further investigation. Not applicable.