Distinct Clinical Phenotypes of Severe Pediatric Influenza in the Post-COVID-19 Era: Insights from a Multicenter PICU Study in Türkiye

Background: Severe pediatric influenza remains a major clinical burden, yet its phenotype in the post-COVID-19 period has not been fully characterized. The pandemic’s infection-control measures created an “immunity gap” among children, altering viral epidemiology and severity. This multicenter study from Türkiye defines the clinical spectrum and outcomes of influenza cases requiring intensive care, providing one of the first regional datasets after the pandemic. Methods: We retrospectively analyzed 85 children with influenza admitted to five tertiary PICUs in İstanbul between 2024 and 2025. Demographics, clinical features and outcomes were compared across groups. Predictors of sepsis, pediatric ARDS, and mechanical ventilation were identified through multivariate logistic regression. Results: Influenza A + RSV co-infection occurred in 14% and affected significantly younger infants, presenting with more severe respiratory distress, hypoxemia, and bronchiolitis. Influenza B was associated with distinct neurotropic features—encephalopathy and seizures in 48%—and a higher risk of sepsis (OR 3.27, 95% CI 1.02–10.53). Hypoxemia, elevated vasoactive–inotropic score, and high PaCO2 independently predicted mechanical ventilation and poor outcomes. Only 2–4% of children had received influenza vaccination. Conclusions: This multicenter analysis reveals a post-pandemic surge of severe pediatric influenza characterized by dual respiratory and neurological phenotypes. RSV co-infection drives early respiratory failure in infants, whereas Influenza B carries a disproportionate risk of neuroinflammation and sepsis. The study provides evidence from Türkiye that the post-COVID “immunity gap” and critically low vaccination coverage contribute to increased PICU admissions. Strengthening pediatric influenza immunization and RSV prevention policies is urgently warranted to mitigate these outcomes.