The older group was made up of 4,469 adolescents, of whom 3,109 (70%) were infected, and 1,360 were uninfected. The average age was 14.8 years, 48% were girls, 73% were White, 21% were Hispanic, and 13% were Black.
"Most research characterizing long COVID symptoms is focused on adults, which can lead to the misperception that long COVID in children is rare or that their symptoms are like those of adults," David Goff, MD, PhD, director for the Division of Cardiovascular Sciences at the NIH’s National Heart, Lung, and Blood Institute, said in an NIH news release.
"Because the symptoms can vary from child to child or present in different patterns, without a proper characterization of symptoms across the life span, it's difficult to know how to optimize care for affected children and adolescents," said Goff, who was not a study author.
Symptom clusters tied to poorer health
In total, 45% of infected and 33% of uninfected school-aged children and 39% of infected and 27% of uninfected adolescents reported at least one persistent symptom, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). Twenty-six symptoms in infected younger children and 18 symptoms in infected adolescents lingered in at least 5% of participants.
Symptom clusters most tied to infection formed the basis of the PASC research index for each age-group and correlated with worse overall health and quality of life. In the younger group, pain and neurocognitive and gastrointestinal symptoms dominate the index, while abnormal smell or taste, pain, and fatigue figure more prominently in adolescents.
PASC index thresholds were established at 5.5 in the younger group and 5.0 older participants. A total of 20% of infected and 4% of uninfected school-aged children and 14% of infected and 3% of uninfected adolescents met or exceeded this threshold. This proportion was higher for participants infected before the SARS-CoV-2 Omicron variant emerged than after (21% vs 14% for younger children and 17% vs 7% for older participants).
The most common long-term symptoms among school-aged children with probable PASC that also contributed to the research index were headache (57%); problems with memory, focus, and sleep (44%); and stomach pain (43%). The most common symptoms that weren't included in the index were pain (51%), daytime sleepiness (49%), and anxiety (47%).
'Similar but distinguishable'
The four symptom clusters in younger children were: (1) high rates of many symptoms; (2) headache (95%), pain (60%), and daytime sleepiness (52%); (3) trouble sleeping (64%) and trouble with memory or focus (62%); and (4) stomach pain (100%) and nausea or vomiting (61%).
Among adolescents, three clusters were identified: (1) high rates of many symptoms, (2) daytime sleepiness (89%) and pain (87%), and (3) impaired smell or taste (100%) and relatively low rates of other symptoms.
Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.
The most common index-contributing persistent symptoms among PASC-probable adolescents were daytime sleepiness (80%), pain (60%), headache (55%), and memory and focus problems (47%). Of symptoms that didn't contribute to the index, the most common were trouble sleeping (47%), anxiety (47%), and depression (38%).
"Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups," the investigators wrote.
In an NYU Langone Health news release, lead author Rachel Gross, MD, professor in the system's Departments of Pediatrics and Population Health, said, "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—but it will likely change and expand as we learn more, and is not intended to be used as a clinical tool today."
4 years on, much remains unknown
In a related editorial, Suchitra Rao, MBBS, of the University of Colorado School of Medicine, said the study may have been limited by the inability to tell whether quality-of-life scores reflected participants' chronic conditions rather than PASC symptoms for those enrolled later in the study, because there were no baseline measurements to determine preinfection status.
"Four years after the initial reports of long COVID, much remains to be discovered regarding the trajectory and strategies for prevention and management, especially in children," she wrote.
"The general and scientific communities, in particular those who continue to endure symptoms on a daily basis, eagerly await the subsequent findings from RECOVER-Pediatrics, which will help uncover more about long COVID in children."
