Associations of age, comorbidities, and inflammatory markers with disease severity in pediatric human metapneumovirus infection

To examine factors associated with severe respiratory disease at initial presentation in pediatric hMPV-associated LRTIs. We analyzed patients aged 1 month to 18 years with PCR-confirmed hMPV-associated LRTI (January 2018-January 2024). Clinical severity was stratified via the Modified Tal Score at admission (mild ≤ 5, moderate 6-10, severe ≥ 11). Each patient contributed one episode. Multivariable binary logistic regression identified risk factors for severe respiratory disease; ROC analysis evaluated biomarker diagnostic accuracy. A total of 676 hMPV-positive patients were identified; after restricting to one episode per patient, 421 unique episodes were analyzed. Of these, 54.9% were mild, 38.5% moderate, and 6.7% (n = 28) severe. Comorbidities were present in 67.9% of severe versus 35.5% of mild cases (p = .004). Viral co-detections occurred in 41.3% but were unrelated to severity (p = .235). Median CRP was 4.0, 10.0, and 32.0 mg/L in mild, moderate, and severe groups, respectively (p < .001). In multivariable regression, comorbidity was the strongest risk factor (OR 2.96, 95% CI 1.17-7.49, p = 0.022), followed by CRP (OR 1.55 per 1 SD [≈32 mg/L], p = 0.018). No age group retained significance after adjustment (model AUC 0.733). CONCLUSIONS: Severe respiratory disease was infrequent (6.7%) and associated primarily with underlying comorbidities, which increased the odds approximately threefold. Age was not independently associated with severity. CRP showed modest diagnostic accuracy (AUC 0.678, negative likelihood ratio 0.59); low levels alone could not reliably exclude severe respiratory disease. WHAT IS KNOWN: • hMPV is an established cause of lower respiratory tract infections in children, Ranging from mild illness to severe pneumonia requiring hospitalization and respiratory support. • Infants younger than 12 months and children with comorbidities such as prematurity, chronic lung disease, congenital heart disease, or neurological disorders carry increased risk for severe hMPV infection. WHAT IS NEW: • Multivariable logistic regression identifies underlying comorbidity as the dominant independent risk factor for severe hMPV respiratory disease (OR 2.96, p = 0.022). No age group retains significance after adjustment, indicating that the apparent severity signal in children older than 5 years reflects a comorbidity-driven population shift rather than older age acting as an independent risk factor. • Elevated CRP, decreased lymphocyte counts, and decreased monocyte counts at admission are associated with severe respiratory disease. CRP retained independent association in multivariable analysis, though diagnostic accuracy for all three biomarkers was modest.