Long COVID in Children and Adolescents

Source: Gross RS, Thaweethai T, Kleinman LC, et al. Characterizing long COVID in children and adolescents. JAMA. Published online ahead of print August 21, 2024; doi: 10.1001/jama.2024.12747.Investigators from multiple institutions conducted a study to describe post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as long COVID, in children. The main aims were to identify common prolonged symptoms in children 6–17 years old after SARS-CoV-2 infection, including in school-age children (6–11 years old) and adolescents (12–17 years old), develop an empirically derived index to identify youths who likely have PASC, and group symptoms into clusters to describe different PASC phenotypes. Participants were enrolled at >60 health care and community settings in the US between March 2022 and December 2023 and included those with a history of prolonged symptoms (>90 days) after their first infection and those who were uninfected (confirmed to be antibody-negative). In addition to providing demographic information, caregivers completed a comprehensive symptom survey about their child that included the presence of 75 symptoms across 9 domains (eg, general, musculoskeletal, behavioral). Multiple statistical techniques were used to identify symptoms that were more common in infected children than in those in the uninfected group. A logistic model was used to develop a score to identify youths likely to have PASC based on reported symptoms. Participants meeting a threshold score were classified as PASC-probable; both infected and uninfected children were included. Finally, regression analyses were used to identify different cluster phenotypes among those in the PASC-probable group.Data were analyzed on 751 infected and 147 uninfected school-age children and 3,109 infected and 1,369 uninfected adolescents. At least 1 prolonged symptom was reported in 45% of infected and 33% of uninfected school-age children, and 39% and 27% of infected and uninfected adolescents, respectively. There were 14 symptoms that were more common in infected than uninfected participants, regardless of age group. In the logistic model, 10 symptoms in school-age children and 8 in adolescents were most associated with infection history. These symptoms were used to develop a threshold score for defining PASC status. Overall, 20% of infected and 4% of uninfected school-age children and 14% and 3%, respectively, of adolescent participants met the threshold score for PASC-probable status. The most common symptoms among PASC-probable school-age children were headache (57%), trouble with memory/focusing (44%), trouble sleeping (44%), and stomach pain (43%). Among PASC-probable adolescents, common symptoms were daytime sleepiness/tiredness (80%), body/muscle/joint pain (60%), headache (55%), and trouble with memory/focusing (47%). Four distinct cluster phenotypes for PASC-probable school-age children and 3 cluster phenotypes among PASC-probable adolescents were identified. One cluster in adolescent participants was distinguished by change/loss in smell or taste.The investigators conclude that specific symptoms can be used to identify youths likely to have PASC.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The estimated prevalence of long COVID, or PASC, in children has varied considerably between studies, from 4% to 66%.1-3 There also is large variation in the reported frequency of persistent symptoms.3 Utilizing analyses like those in the adult National Institutes of Health-funded Researching COVID to Enhance Recovery (RECOVER) Consortium,4 the authors characterized pediatric PASC symptoms. Symptom patterns were similar but distinguishable between school-age children and adolescents. Like adults, adolescents, as compared to school-age children, were more likely to report loss of or change in smell or taste. These identified phenotypic PASC presentations can be used in subsequent research to assess clinically useful markers of PASC.5Currently, there is no set of clinical symptoms, signs, or laboratory values to diagnose PASC.6 A multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of PASC in children and adolescents is available.3 It is difficult to sort out the contribution of the impact of the pandemic on symptoms such as fatigue and depression, because these symptoms also have been reported among uninfected children, adolescents, and adults.1,2While research is ongoing to better understand the pathogenesis behind PASC and optimal treatment approaches, there is a prevention option that can be more strongly encouraged. A recent study among cohorts of vaccinated and unvaccinated patients <18 years old showed that vaccination against COVID-19 was associated with a reduced risk of long COVID for at least 12 months.7 Vaccine effectiveness was higher in adolescents, who have a higher risk of long COVID, compared to younger children.Specific symptom patterns can be used to identify and distinguish between PASC in children and adolescents. Vaccination against COVID-19 reduces the risk of PASC.Although the RECOVER-Pediatrics cohort is large and geographically diverse, study limitations ought to be recognized when assessing its findings. Recruitment strategies may have resulted in a higher proportion of children with neuro-behavioral symptoms than previously reported.5 Caregivers provided evaluations, which can contribute to symptom underreporting and recall bias.