Characterizing Long COVID in Children and Adolescents. 2024, Rachel S. Gross, MD, MS et al

Key Points

Question What prolonged symptoms experienced by youth are most associated with SARS-CoV-2 infection?

Findings Among 5367 participants in the RECOVER-Pediatrics cohort study, 14 symptoms in both school-age children (6-11 years) and adolescents (12-17 years) were more common in those with vs without SARS-CoV-2 infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. Empirically derived indices for PASC research and associated clustering patterns were developed.

Meaning This study developed research indices for characterizing pediatric PASC. Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.

Abstract
Importance Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

Objective To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Design, Setting, and Participants Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

Exposure SARS-CoV-2 infection.

Main Outcomes and Measures PASC and 89 prolonged symptoms across 9 symptom domains.

Results A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise–related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

Conclusions and Relevance This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

LINK

 

This is in JAMA. It should be open-access. Rapid summary —

• The analytic sample included individuals aged 6 to 17 years enrolled between March 16, 2022, and December 16, 2023, with and without known SARS-CoV-2 infection history (infected and uninfected, respectively). Child age was recorded at symptom survey completion.

• the infected group included participants who completed their survey about prolonged symptoms at least 90 days after their first infection,reportedbytheir caregivers

• SARS-CoV-2 antibodies were not required.

• uninfected group was defined by caregiver report and required confirmation of negative nucleocapsid antibodies at enrollment.

• Those thought to be uninfected but found to be antibody-positive (Ab+) within 30 days of survey completion were analyzed separately to understand asymptomatic infection.

• Throughout, uninfected refers strictly to uninfected participants who were confirmed to be nucleocapsid antibody–negative.

• If a symptom lasted for more than 4 weeks but was absent at survey completion, it was not counted as a prolonged symptom.

• This study included 751 infected and 147 uninfected school-age children and 3109 infected and 1369 uninfected adolescents

• Overall, 45% of infected (338/751) and 33% of uninfected (48/147) school-age children and 39% of infected (1219/3109) and 27% of uninfected (372/1369) adolescents reported having at least 1 prolonged symptom.

• In both age groups, higher PASC research indices were correlated with worse PROMIS scores (Figures 2C and 3C). The number of systems affected among infected PASC-probable participants (eFigure 4 in Supplement 3) indicated substantial multisystem burden.

• The most common prolonged symptom among PASC-probable school-age children that also contributed to the PASC research index (Figures 2B and 4) was headache (57%), followed by trouble with memory/focusing and trouble sleeping (44%) and stomach pain (43%). Among symptoms that did not contribute to the index, body/muscle/joint pain (51%), daytime tiredness/

• sleepiness or low energy (49%), and feeling anxious (47%) were the most common (Figure 4). The distribution of symptoms was similar between PASC-unspecified and uninfected school-age children.

• AmongPASC-probable adolescents, the most common prolonged symptoms contributing to the index (Figures 3B and 4) were daytime tiredness/sleepiness or low energy (80%), body/muscle/joint pain (60%), headaches (55%), and trouble

• with memory/focusing (47%). Among symptoms that did not contribute to the index, trouble sleeping (47%), feeling anxious (47%), and feeling sad/depressed (38%) were the most common (Figure 4).

• Among school-age children, 4 symptom clusters

• Cluster 1 had high rates of many symptoms and the highest symptom burden.

• Cluster 2 was characterized by high rates of headache (95%), body/muscle/joint pain (60%), and daytime tiredness/sleepiness or low energy (52%).

• Cluster 3 was characterized by higher rates of trouble sleeping (64%) and trouble with memory/focusing (62%).

• Cluster 4 was characterized predominantly by stomach pain (100%) and nausea/vomiting (61%).

• Among adolescents, 3 clusters were identified

• Cluster 1 had high rates of many symptoms

• Cluster 2 was characterized by high rates of daytime tiredness/ sleepiness or low energy (89%) and body/muscle/joint pain (87%).

• Cluster 3 was characterized by having change/loss in smell or taste (100%), with relatively low rates of all other symptoms.

• Overall, 64 school-age children and 781 adolescents enrolled as uninfected but were Ab+ (ie, asymptomatically infected)

• In this cohort, 20% of infected school-age children exceeded the PASC symptom threshold, while 14% of adolescents exceeded the threshold.

• Most research to understand PASC symptoms has focused on adults, potentially due to the misperception that children were not severely affected by COVID-19, leaving childhood symptoms less understood.

• The current study had the advantage of comprehensively assessing caregiver-reported symptoms across every organ system, examining them in combination, and comparing them directly to an uninfected seronegative control group. The symptoms identified as being related to PASC were associated with infection, not only symptoms that became more common during the pandemic.

• These findings underscore the need for separate assessments in different age groups. This may be one reason that younger children with PASC are being undercounted in studies and/or undiagnosed clinically, although undercounting may also be due to younger children being less able to recognize and report symptoms.

• The pathophysiology behind these age-related differences warrants future study, given substantial changes in growth, development, immunological factors, and pubertal hormones that occur across the life course.

 

I'm baffled by the overarching claim about symptoms being that different. The differences are trivial. And they don't appear to have included the more typical symptoms that are characteristic of LC like PEM, which makes it an undercount. We pretty much see the same rough clusters in adults, again likely mostly noise based on time and respondents, and in those there is usually a lot of fluctuations. FFS the very first Body Politic paper had an absolutely fantastic breakdown of symptoms over time whose quality has yet to be matched by pros with millions in budgets.

I get that medicine wants the whole "anecdotes aren't data" but anecdotes usually relate to one, maybe a handful of examples, not literally millions, and starting with thousands within the first year. This was never anecdotal, it was always rough data. At this point it was like a huge flooding, you don't need hydrographers to confirm that there is a huge flood, eyeballs are more than enough when it's that big.

Good timing with the recent retraction of the minimizing paper.