A landmark 2024 study in JAMA introduces two novel research indices for identifying children and adolescents mostly likely to have long COVID. The study, led by the NIH’s RECOVER Initiative and supported by its Clinical Science Core (CSC) at NYU Langone Health, is the first to apply a data-driven approach to characterize long COVID symptom patterns in children and teens, revealing distinct differences from those observed in adults—a population that has been the primary focus of most long COVID research.
Long COVID remains challenging to diagnose as its clinical manifestations are diverse and symptom patterns often vary widely from patient to patient. Although the research indices are not intended for clinical diagnoses, they mark an important first step toward the development of a clinically useful tool for identifying long COVID in kids.
Here, we highlight the study’s approach, key findings, and what’s next for the research.
What was the study design?
The observational study included two cohorts: 898 school-age children (6 to 11 years) and 4,469 adolescents (12 to 17 years). Roughly three-quarters of the participants in each cohort had experienced a SARS-CoV-2 infection, while one-quarter were uninfected. Patients were enrolled at more than 60 healthcare institutions across the United States.
The researchers looked for long-term symptoms that were more common among the participants with a history of SARS-CoV-2 infection compared to those with no history of infection.
What symptoms were identified in children?
In school-age children, 10 symptoms were identified as the most predictive of long COVID: trouble with memory or focusing, back or neck pain, stomach pain, headache, phobias, refusing to go to school, itchy skin or rash, trouble sleeping, nausea or vomiting, and feeling lightheaded or dizzy.
What symptoms were identified in adolescents?
In adolescents, 8 symptoms were most predictive of long COVID: change or loss of smell and/or taste, body, muscle or joint pain, daytime tiredness, tiredness after walking, back or neck pain, trouble with memory or focusing, headache, and feeling lightheaded or dizzy.
These symptoms in school-age children and adolescents were used to develop the two respective research indices.
Are these lists of symptoms exhaustive? Does a patient need to have more than one symptom to be considered as having long COVID?
The answer to both is no, says principal investigator Rachel S. Gross, MD, the corresponding study author and director of pediatric research for the RECOVER CSC at NYU Langone. “We recognize that any one symptom, including those not in the index, may be sufficient to indicate the presence of long COVID in any given child,” says Dr. Gross, who is also an associate professor of pediatrics and population health at NYU Langone.
What were the other key findings from the study?
The researchers found that children and teens with prolonged COVID symptoms experienced them in almost every organ system, with most patients having multisystem involvement. They also found four distinct symptom clusters in school-age children and three in adolescents. The existence of the groups suggests that there may be different types of long COVID that children experience.
Moving forward, the research team will seek to determine whether these pediatric clusters are associated with different disease mechanisms, which would be critical in identifying treatment targets for future pediatric clinical trials.
What’s next for this work?
The study authors hope the indices will support further data-driven research into long COVID in pediatric patients. Researchers interested in applying the indices in their research can access datasets for both the RECOVER pediatrics and adult cohorts here.
“Our research index is a first step toward a tool that could someday be used to identify long COVID in children and adolescents—a widely understudied group,” says Dr. Gross. “But it will likely change and expand as we learn more, and is not intended to be used as a clinical tool today.”
