Phenotyping Pediatric Long COVID: Symptom Clusters from a Longitudinal Multicenter Italian Cohort

Highlights: What are the main findings? In a longitudinal cohort of 850 children, cluster analysis identified three age-related trajectories. Young children (0–5 years) mainly had respiratory symptoms and higher hospitalization risk, with sequelae often persisting; older children (6–11 years) experienced mild disease and good recovery; adolescents (12–17 years), particularly females, showed more severe acute symptoms and were most affected by long-term neuropsychological sequelae like fatigue and insomnia. What are the implications of the main findings? Pediatric PASC management should be age-tailored: vaccination and respiratory follow-up should be reinforced in young children, and neuropsychological support should be prioritized for adolescent girls. Future research should confirm these patterns in larger groups of people, observe how they change over time, and combine biological and psychosocial information, as well as potential biomarkers and objective measures (e.g., neurocognitive testing and pulmonary function), to help design prevention and intervention strategies. Background: The aim of this study was to identify patient clusters based on acute symptom profiles and individual characteristics most likely to develop pediatric post-acute sequelae of SARS-CoV-2 infection (PASC), as well as clusters among patients with PASC based on post-acute sequelae and associated characteristics. Methods: This multicenter cohort study in 12 Italian pediatric units enrolled patients aged 0–17 years within three months of a laboratory-confirmed SARS-CoV-2 infection. Participants who completed at least two surveys developed by the ISARIC over one year were analyzed. PASC was defined per WHO criteria. Multiple Correspondence Analysis and Hierarchical Clustering were performed. Results: Of 1137 children enrolled, 850 (76%) completed at least two surveys. The most prevalent age group was older children (6–11 years) (46%); adolescents (12–17) and young children (0–5) were numerically similar. Males were more represented (51.9%), except for the adolescent group (45.1%). PASC occurred in 32.8% of participants, with the distribution of sequelae types varying by age. Clustering in COVID-19 cases identified three clusters: young children mainly presented with respiratory symptoms and with a higher risk of hospitalization, while older children were spared in both acute and post-acute phases. Adolescents, particularly females, reported more pronounced acute symptoms and developed PASC more frequently. Clustering analysis of cases with PASC identified three clusters, confirming these age-related patterns. Young children still exhibited respiratory sequelae, and older children confirmed good recovery with minimal complications, while adolescents, especially females, remained the most affected subgroup, reporting persistent neuropsychological sequelae such as fatigue and insomnia. Conclusions: Findings support age-tailored follow-up, emphasizing respiratory monitoring for young children and targeted neuropsychological care for adolescents, particularly girls.