Study of 172,136 children and young adults finds elevated BMI linked to increased PASC risk: 25.4% higher for obesity and 42.1% for severe obesity.

In a cohort study published in JAMA Network Open, researchers from the United States of America (US) investigated the relationship between body mass index (BMI) status before coronavirus disease 2019 (COVID-19) and the risk of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) in children.

They found that higher BMI, specifically obesity and severe obesity, was associated with an increased risk of developing PASC, with the risk rising in a dose-dependent manner relative to BMI.

Background

Pediatric PASC is a complex condition involving persistent, relapsing, or new symptoms appearing at least 4 weeks after acute COVID-19. Its impact spans multiple organ systems, with prevalence estimates ranging widely from 1.6% to 70% across studies. The condition represents a significant risk to children, emphasizing an urgent need to understand its causes, as highlighted by the National Institute for Health and Care Excellence.

Although obesity is a well-known chronic condition linked to severe COVID-19 outcomes even in the US, most research on obesity-related PASC risk has centered on adults. While some studies have explored PASC in children with obesity, the specifics of this association, especially its dose-response relationship, remain underexplored, pointing to a critical gap with important implications for pediatric health.

In the present study, researchers examined the potential link between pre-infection BMI and PASC outcomes, with the aim of guiding prevention and care for at-risk pediatric patients.

About the study

In the present retrospective cohort study, researchers used deidentified data from 26 US institutions. They analyzed pediatric COVID-19 outcomes with contributions from hospitals and outpatient settings. Data were obtained from electronic health records (EHR) between March 2020 and May 2023 of children under 21 years of age with documented SARS-CoV-2 infection. Participants were excluded if they were under five years of age at BMI assessment or had genetic or medical conditions affecting weight.

A total of 172,136 participants were included. The mean age of participants was 12.6 years at BMI assessment; 52.4% were female, and 50.7% were non-Hispanic White. BMI categories were based on age-specific growth chart percentiles given by the Centers for Disease Control and Prevention or adult BMI ranges for individuals above 19 years of age.

PASC was identified using codes from the International Classification of Diseases 10^th revision for post-COVID conditions, as well as clusters of 24 symptoms and conditions representing PASC phenotype. Variables such as age, sex, race/ethnicity, COVID-19 variant, healthcare utilization, comorbidity index, COVID-19 severity, vaccination status, and insurance type were also included in the study.

The follow-up period lasted from 28 days to 179 days after the index date, which was either the earliest date of COVID-19 diagnosis or 28 days before the diagnosis of PASC or multisystem inflammatory syndrome. Statistical analysis involved the use of Poisson and modified Poisson regression, orthogonal trend analysis, and several post hoc sensitivity analyses.

Results and discussion

About 49.7% of the participants had obesity or severe obesity. During the follow-up, 0.8% of participants were diagnosed with PASC. About 26.4% of participants experienced at least one PASC symptom, with similar obesity rates. Participants with higher BMI showed an elevated risk of PASC and PASC-related symptoms compared to those with a relatively lower BMI. A dose-response effect was observed. Specifically, participants with obesity and severe obesity showed a higher risk of receiving a PASC diagnosis (relative risks [RRs] were 1.25 and 1.42, respectively) and of experiencing any PASC symptoms or conditions (RR 1.11 and 1.17, respectively).

Subgroup analyses largely supported these findings, but associations with BMI and PASC were significant only among non-Hispanic White participants, not among non-Hispanic Black or Hispanic participants. Sensitivity analyses confirmed the dose-response pattern. A negative control outcome analysis showed no residual bias, suggesting that the findings were robust.

This is the first study to investigate the link between BMI status and PASC among children, further strengthened by its large sample size. However, the study is limited by a potential sample skewness due to high obesity prevalence, absence of modifiable risk factors like diet and activity, possible overclassification of PASC without standardized criteria, symptom overlap with obesity-related conditions, and selection bias from overrepresentation of severe cases, despite efforts to include broader outpatient data.

Conclusion

In conclusion, the study identified a strong link between higher pre-COVID-19 BMI and increased PASC risk in children, emphasizing the need for proactive monitoring and personalized care for those with elevated BMI. The findings call for public health efforts to promote healthy lifestyle choices and manage obesity as a modifiable risk factor to reduce PASC burden and improve pediatric health outcomes in the post-pandemic era. Further research is warranted to explore specific BMI-related PASC symptoms.