Distinguishing active pediatric respiratory infection from upper respiratory tract colonization and interpreting etiology from routine host laboratory markers remains a significant clinical challenge. This study evaluated the detection spectrum of pediatric respiratory pathogens and examined exploratory associations with routine inflammatory and hematological biomarkers. A retrospective surveillance of 784 PCR-positive pediatric cases (aged 0–18 years) was conducted between October 2024 and June 2025. Pathogen profiles, temporal dynamics, codetection patterns, and associations with C-reactive protein (CRP), albumin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were evaluated. Multiplex PCR revealed a polymorphic landscape with a 51.7% codetection rate. Viruses predominated (60.5%), led by rhinovirus/enterovirus (32.1%), influenza viruses (26.1%), RSV (16.6%), and adenovirus (14.8%). S. pneumoniae (38.9%) and H. influenzae (31.6%) were the most prevalent bacterial targets among expanded panel tests. Influenza detections were associated with significantly lower median ANC ( p < 0.001), whereas adenovirus showed elevated CRP and ANC ( p < 0.001). Mycoplasma pneumoniae exhibited elevated CRP and relative lymphopenia ( p < 0.001). S. pneumoniae detection showed no significant correlation with CRP elevation ( p = 0.181), whereas H. influenzae was associated with higher median CRP levels ( p < 0.001). Routine host biomarkers demonstrate distinct observational associations across viral and bacterial PCR detection groups. However, molecular detection of commensal bacteria on nasopharyngeal specimens must be interpreted cautiously alongside systemic inflammatory markers to avoid overattributing active disease to simple colonization.
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