There is a wide variety of symptoms of long COVID, but they also appear to be different in adults than in children and adolescents, as revealed by a new study published in the journal JAMA Network, in which researchers decided to characterize long COVID in childhood and adolescence, examining the most common symptoms of this disease in children aged 6 to 11 years and adolescents aged 12 to 17 years.
A team of researchers led by the National Institutes of Health’s RECOVER Initiative and supported by its Clinical Sciences Center (CSC) at NYU Langone Health has created a new way to identify children and adolescents most likely to develop long COVID.
Long COVID is a condition characterized by COVID-19 symptoms that persist, relapse, or develop two or more months after recovery from the initial SARS-CoV-2 infection. An estimated 65 million people worldwide are living with long COVID, and its global health effects are expected to last for decades.
The researchers classified long-COVID symptoms in the pediatric population into distinct phenotypes using a cluster analysis. They also used the results of these investigations to develop an empirical index, which will allow future researchers greater clarity when diagnosing and treating this condition.
The findings revealed that the pathology of long COVID in childhood is different compared to adults, and also varies between children and adolescents. Symptoms were observed to take 10% longer to manifest in adolescents than in children (556 days vs. 506 days).
Distinct symptom clusters in school-aged children and adolescents
The NIH RECOVER Initiative aims to fill gaps in knowledge by conducting a comprehensive study of this condition. The current study included 751 SARS-CoV-2-infected and 147 uninfected school-aged children, along with 3,109 infected and 1,369 uninfected adolescents, across more than 60 healthcare facilities in the United States. The study index used distinct symptom combinations for each age group (10 symptoms in school-aged children and 8 in adolescents) to indicate the likely presence of long COVID.
Children and adolescents were found to experience prolonged symptoms following SARS-CoV-2 infection across nearly all organ systems, with the majority having symptoms affecting more than one system. A clear pattern of symptom differences was observed between school-aged children (6–11 years) and adolescents (12–17 years), underscoring the need for RECOVER and other studies that track long COVID over time as children develop.
“Our research index is a first step toward creating a tool that could be used in the future to identify long COVID in children and adolescents, a group that has been vastly understudied. However, this index is likely to change and expand as we learn more, and it is not intended to be used as a clinical tool at present,” said senior study author Dr. Rachel S. Gross, an associate professor in the Departments of Pediatrics and Population Health at NYU Langone.
“We also found an association between the study index and overall health, physical health, and quality of life, underscoring the significant impact long COVID has on children and adolescents,” added study co-senior author Dr. Melissa Stockwell, chief of the Division of Child and Adolescent Health and the Felice K. Shea Professor of Pediatrics at Columbia University Irving Medical Center, who is also chair of the RECOVER Pediatric Coordinating Committee.
The original list of symptoms was narrowed down to include only those present in at least 5% of children or adolescents with a history of COVID-19 infection. The study authors then used a series of statistical techniques to determine the odds of a person having each persistent symptom, comparing those who had been previously infected to those who had never been infected.
“Our research index is a first step towards creating a tool that could be used in the future to identify long COVID in children and adolescents”
Among the 5,376 study participants, researchers found that 18 symptoms in school-aged children and 17 in adolescents were more common in those with a history of COVID infection compared with those without, with 14 symptoms shared between the two age groups.
The researchers then employed a statistical technique called LASSO to determine the most predictive long-term COVID-19 symptoms and included these in their ‘PASC research index’ – PASC refers to the technical name for long COVID, post-acute sequelae of SARS-CoV-2 infection.
Symptoms included in the index for children were memory or concentration problems, back or neck pain, abdominal pain, headache, phobias, refusing to go to school, itchy skin or rash, trouble sleeping, nausea or vomiting, and feeling dizzy or lightheaded. In adolescents, the most predictive symptoms were change or loss of smell or taste; body, muscle, or joint pain; daytime tiredness; tiredness when walking; back or neck pain; memory or concentration problems; headache; and feeling dizzy or lightheaded.
Interestingly, the research team found that the proportion of children who reported at least one symptom was not that different between those with and without a previous COVID infection. The research index (which measured a cluster of symptoms) was more effective at distinguishing between those with and without a history of infection.
Ultimately, the researchers found four distinct symptom clusters in school-aged children and three in adolescents, suggesting that there may be different types of long COVID in children. Moving forward, the research team will seek to determine whether these pediatric clusters are associated with different disease mechanisms, which would be crucial for identifying treatment targets in future pediatric clinical trials.
