More than a dozen long COVID symptoms overlapped between school-age kids and adolescents, yet differences did emerge in a large longitudinal observational study of U.S. children.
In models adjusted for sex, race, and ethnicity, 14 prolonged symptoms in kids ages 6-11 years and adolescents ages 12-17 years were more common in those with a history of COVID-19 compared with those without a history, with four distinct symptom phenotypes in school-age children and three in adolescents, reported Rachel Gross, MD, of NYU Grossman School of Medicine in New York City, and colleagues in .
Researchers identified 18 prolonged symptoms that were more common in school-age children, including headache (57%), trouble with memory or focusing (44%), trouble sleeping (44%), and stomach pain (43%). In adolescents, 17 symptoms were more common, including daytime tiredness/sleepiness or low energy (80%); body, muscle, or joint pain (60%); headaches (55%); and trouble with memory or focusing (47%).
Among school-age children, four clusters included a group comprising multiple body system involvement; headache, musculoskeletal pain, and low energy/sleepiness; trouble sleeping and trouble with memory/focusing; and gastrointestinal manifestations. For adolescents, three clusters included multiple body symptoms, musculoskeletal pain and low energy/sleepiness, and change or loss of smell or taste.
Combinations of symptoms most associated with infection history were identified to form a long COVID research index for each age group, Gross and team noted, adding that these indices correlated with poorer overall health and quality of life.
"At present, the majority of long COVID research has been centered around adults," Gross told . "This lack of focus on the pediatric population has led to major gaps in our understanding of how long COVID affects children -- making this study a critical step forward in pediatric long COVID research."
"In exploring different groupings of symptoms across a wide range of childhood ages, RECOVER [trial] researchers found that while many of the long COVID symptoms were similar, they were also distinguishable from each other," she said. "For example, we found four distinct symptom clusters in school-age children and three in adolescents, indicating there may be several types of long COVID that children experience, and these may vary as children grow and develop."
"This shows us that a one-size-fits-all approach would likely not be effective in diagnosing children with long COVID," she added. "Rather, it is likely that future screening or diagnostic tools -- as well as treatments -- will need to be tailored for specific age groups."
In an , Suchitra Rao, MBBS, MSCS, of the University of Colorado School of Medicine and Children's Hospital Colorado in Aurora, noted that taken with the adult RECOVER study published in 2023, "the publications highlight the importance of evaluating chronic conditions such as [long COVID] across the life spectrum because there were clear differences in presentations among children, adolescents, and adults."
She pointed out that headaches were common in children, but were less prominent in adolescents and adults. In addition, "a gastrointestinal symptom cluster was unique to school-age children, whereas gastrointestinal symptoms were more likely to be present in conjunction with other symptoms in adults," she wrote.
Gross said that this study was "a first step toward a future tool to identify long COVID in children and adolescents and is expected to change as researchers learn more."
"As such, it is not intended for clinical use at this time," she noted. "Instead, we hope this lays the foundation for future pediatric long COVID research. We also hope that these findings will help families, clinicians, and healthcare teams by raising awareness about long COVID, showing that children can develop long COVID and that their symptoms may be different from those in adults."
For this study, participants were recruited from more than 60 healthcare and community settings in the U.S. from March 2022 to December 2023. Their caregivers completed a survey that assessed 89 prolonged symptoms across nine domains. Median time between first infection and survey was 506 days for school-age kids and 556 days for adolescents.
Prolonged symptoms were those lasting more than 4 weeks, and that started or became worse since the beginning of the pandemic, and that were present at the time of survey completion (at least 90 days after infection).
Gross and team included 751 school-age kids with previous SARS-CoV-2 infection and 147 with no previous infection. Mean age was 8.6 years, 49% were girls, 60% were white, 34% were Hispanic/Latino/Spanish, and 11% were Black or African American.
They also included 3,109 adolescents with previous SARS-CoV-2 infection and 1,360 without previous infection. Mean age was 14.8, 48% were girls, 73% were white, 21% were Hispanic/Latino/Spanish, and 13% were Black or African American.
Overall, 45% of infected and 33% of uninfected school-age children, as well as 39% of infected and 27% of uninfected adolescents, reported having at least one prolonged symptom. Additionally, 26 symptoms in infected kids and 18 symptoms in infected adolescents were prolonged in at least 5% of participants.
Of the 751 infected kids, 20% met the long COVID research index threshold, as did 14% of the infected adolescents.
Limitations included that children may have had long COVID without meeting the index threshold. In addition, some participants in the infected and uninfected groups could have been misclassified. Recall bias was also possible, since symptoms were caregiver-reported.
Disclosures
The study was funded by the NIH.
Gross had no disclosures. Co-authors reported relationships with educational institutions, federal agencies, pharmaceutical and other companies, and medical associations or groups. They also reported holding software patents.
Rao reported receiving grants from the National Heart, Lung, and Blood Institute; the CDC; the Patient-Centered Outcomes Research Institute; and the Agency for Healthcare Research and Quality.
Primary Source
JAMA
Gross RS, et al "Characterizing long COVID in children and adolescents" JAMA 2024; DOI: 10.1001/jama.2024.12747.
Secondary Source
JAMA
Rao S "Uncovering long COVID in children" JAMA 2024; DOI: 10.1001/jama.2024.13551.