Post-acute symptom persistence following SARS-CoV-2, RSV, and influenza in children: A retrospective cohort study

Persistent symptoms following acute viral respiratory infections are increasingly recognized in children. While post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; long COVID) have been extensively studied, whether comparable post-acute morbidity occurs after other major respiratory viruses and whether clinical patterns differ across pathogens remains incompletely characterized. This retrospective cohort study included children aged 0 to 18 years with reverse transcription polymerase chain reaction-confirmed SARS-CoV-2 (n = 1540), respiratory syncytial virus (RSV; n = 2150), or influenza (n = 2050) infections evaluated between January 2020 and December 2024 at a tertiary university hospital system in Istanbul, Turkey. Persistent symptoms were assessed at clinician-documented follow-up visits 4 to 6 weeks after virological diagnosis. Multivariable logistic regression identified independent predictors for each pathogen. Bonferroni correction was applied for multiple comparisons. Model calibration was assessed using the Hosmer-Lemeshow test, and discriminative ability by the area under the receiver operating characteristic curve. Among 5740 children, persistent symptoms at 4 to 6 weeks were documented in 24.0% (95% confidence interval [CI] = 22.2-25.8) with RSV, 22.0% (95% CI = 19.9-24.1) with SARS-CoV-2, and 21.2% (95% CI = 19.4-23.0) with influenza (P = .086). While overall post-acute prevalence was comparable across the 3 viruses, symptom profiles differed markedly: RSV-related post-acute morbidity was dominated by respiratory and feeding difficulties in young infants; SARS-CoV-2 predominantly produced neurocognitive and systemic complaints in school-aged children; and influenza was characterized by sustained systemic symptoms. Hypoxemia was the strongest predictor for RSV (adjusted odds ratio [aOR] = 2.4, 95% CI = 1.7-3.3), while age >6 years (aOR = 2.1, 95% CI = 1.5-2.9) and hospitalization (aOR = 1.9, 95% CI = 1.4-2.6) were leading predictors for SARS-CoV-2. Age-stratified analyses demonstrated a significant virus × age interaction (P < .001), with the highest prevalence observed after RSV among infants and after SARS-CoV-2 among school-aged children. Hosmer-Lemeshow testing confirmed adequate calibration for all models (all P > .05). Inverse probability weighting sensitivity analysis yielded consistent results. Post-acute symptom persistence following pediatric viral respiratory infections is common and follows virus-specific patterns. Overall post-acute symptom prevalence was comparable across the 3 viruses, but symptom profiles were strikingly virus-specific and age-dependent. This direct comparison of 3 major respiratory viruses demonstrates that post-acute morbidity extends beyond SARS-CoV-2 and varies by pathogen and age. These findings support the development of pathogen-informed follow-up considerations.