A new study may have shed light on the complex presentation of long COVID, or postacute sequelae of SARS-CoV-2 infection, in children aged 6 to 17 years.

In the comprehensive, multicenter, longitudinal, observational cohort study, published in JAMA, investigators aimed to characterize the most common prolonged symptoms, their differences between school-age children (6 to 11 years) and adolescents (12 to 17 years), symptom clustering into distinct phenotypes, and the development of an empirically derived symptom index for Postacute sequelae of SARS-CoV-2 infection (PASC) research.

Conducted by the RECOVER-Pediatrics Consortium, the study included 898 school-age children (751 infected, 147 uninfected) and 4,469 adolescents (3,109 infected, 1,360 uninfected) recruited from over 60 U.S. health care and community settings between March 2022 and December 2023. PASC was defined as having any of 89 prolonged symptoms across 9 domains lasting more than 4 weeks postinfection.

Among the key findings were:

• In adjusted models, 14 symptoms were more common in both age groups with prior infection, with four additional symptoms specific to school-age children (poor appetite, palpitations during exercise, lightheadedness/dizziness, and nausea/vomiting) and three to adolescents (change/loss in smell/taste, lightheadedness/dizziness, and panic attacks).
• Using LASSO regression, PASC research indices were developed: 10 symptoms for school-age children (trouble with memory/focusing, pain, stomach issues, headache, and anxiety) and eight for adolescents (fatigue, pain, headache, memory/focus issues, and smell/taste changes). Higher scores correlated with poorer health and quality of life.
• Index thresholds were set at 5.5 for school-age children and 5.0 for adolescents. About 20% of infected school-age children and 14% of adolescents met these thresholds compared with 4% and 3% of uninfected peers, respectively. Rates were higher pre-Omicron: 21% vs 14% in school-age school-age children and 17% vs 7% in adolescents.
• Four PASC phenotype clusters were identified in school-age children: high symptom burden, fatigue/pain predominant, neuropsychological/sleep, and gastrointestinal. Adolescents had three: high symptom burden, fatigue/pain, and smell/taste predominant.
• Among PASC-probable children, the high symptom burden clusters had the most affected organ systems (mean 6.7 in school-age children vs 7.4 in adolescents).

The investigators concluded that the study provided vital insights into pediatric PASC characterization, underscoring differences between school-age children and adolescents. The developed PASC research indices offer a framework for future studies on risk factors, pathophysiology, recovery, and relapse. However, the indices are not yet intended for clinical diagnosis, which should incorporate individual clinical judgment.

Conflict of interest disclosures can be found in the study.