A large-scale study of postacute sequelae of SARS-CoV-2 infection, or long COVID, in children and adolescents identified distinct symptom patterns between school-age children (6-11 years) and adolescents (12-17 years).
The report, published in JAMA, developed research indices to characterize pediatric postacute sequelae of SARS-CoV-2 infection (PASC) and identified multiple symptom clusters. The RECOVER-Pediatrics cohort study analyzed data from 898 school-age children (751 with previous SARS-CoV-2 infection and 147 without) and 4,469 adolescents (3,109 infected and 1,360 uninfected). The median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents.
Key Findings
Fourteen symptoms were more common in both age groups with a SARS-CoV-2 infection history compared to those without, with 4 additional symptoms in school-age children only and 3 in adolescents only.
Twenty percent of infected school-age children and 14% of infected adolescents exceeded the PASC symptom threshold developed by the researchers.
Four distinct symptom clusters were identified in school-age children and three in adolescents.
Higher PASC research indices correlated with worse overall health and quality of life scores.
Methods and Further Research Highlights
The study used a comprehensive symptom survey assessing 89 prolonged symptoms across 9 domains. Symptoms were considered prolonged if they lasted more than 4 weeks, started or worsened since the beginning of the pandemic, and were present at the time of survey completion (at least 90 days after infection).
To identify combinations of symptoms most associated with infection history, the researchers used a penalized logistic regression approach (least absolute shrinkage and selection operator [LASSO]). This resulted in PASC research indices for each age group, with optimal thresholds of 5.5 for school-age children and 5.0 for adolescents.
For school-age children, the 10 symptoms contributing to the PASC research index were: trouble with memory or focusing, back or neck pain, stomach pain, headache, fear about specific things, refusing to go to school, itchy skin or skin rash, trouble sleeping, nausea or vomiting, and feeling lightheaded or dizzy. For adolescents, the eight symptoms were: change or loss in smell or taste, body/muscle/joint pain, daytime tiredness/sleepiness or low energy, feeling tired after walking, back or neck pain, trouble with memory or focusing, headache, and feeling lightheaded or dizzy.
The most common prolonged symptoms among PASC-probable school-age children were headache (55%), trouble with memory/focusing (45%), trouble sleeping (44%), and stomach pain (43%). Among PASC-probable adolescents, the most common symptoms were daytime tiredness/sleepiness or low energy (80%), body/muscle/joint pain (61%), headaches (56%), and trouble with memory/focusing (47%).
Using K-means consensus clustering, the researchers identified four symptom clusters in school-age children and three in adolescents. The clusters with the highest symptom burden in both age groups were correlated with poorer overall health and quality of life.
The study also found that the percentage of participants meeting the PASC threshold was higher for those infected before vs after the emergence of the Omicron variant (21% vs 14% for school-age children; 17% vs 7% for adolescents).
Additional demographic data showed that the mean age was 8.6 years for school-age children (49% female) and 14.8 years for adolescents (48% female). Race and ethnicity breakdown for school-age children was 11% Black or African American; 34% Hispanic, Latino, or Spanish; and 60% White. For adolescents, it was 13% Black or African American; 21% Hispanic, Latino, or Spanish; and 73% White.
Vaccination status at the time of first infection (for infected) or enrollment (for uninfected) participants varied between groups. Among school-age children, 26% of infected and 67% of uninfected participants were fully vaccinated. For adolescents, 43% of infected and 77% of uninfected participants were fully vaccinated.
The study also examined asymptomatic infections, finding that 64 school-age children and 781 adolescents enrolled as uninfected but were antibody-positive (Ab+). Among Ab+ school-age children, 9% met the index threshold and 28% reported at least one prolonged symptom; for Ab+ adolescents, 4% met the index threshold and 22% reported at least one prolonged symptom.
Statistical methods included linear, logistic, and Poisson regression to estimate risk difference, odds ratio, and relative risk for infected vs uninfected participants. LASSO was used to identify symptoms best at differentiating participants with or without infection history, while K-means consensus clustering identified distinct PASC symptom profiles.
The researchers noted that symptom frequency did not change meaningfully when comparing different times between infection and survey completion. They also observed that the strongest differentiators of infection history in adults and adolescents overlapped considerably, but there was less overlap between adults and school-age children.
Limitations of the study included potential selection bias, reliance on caregiver-reported symptoms, and the possibility of misclassification in the infected and uninfected groups. The study design did not allow for determination of population prevalence of pediatric PASC.
Conflict of interest disclosures can be found in the study.
