Key Clinical Summary: Who should be considered high risk for COVID-19 disease severity?

This is a micro-learning module summary of the session by Prof. Buddy Creech which you can find here. Before participating, please read our CME and disclosure information which can be found here.

Acknowledgment: This program is supported by an independent education grant from Pfizer Global Medical Grants. This online education program has been designed solely for U.S. healthcare professionals only. The content is not available for healthcare professionals in any other countries.

Introduction

This summary explores current evidence defining high‑risk groups among children and adolescents, outlining the risk factors and key comorbidities associated with increased morbidity, including population‑level data on the relative contribution of underlying medical conditions,and practical recommendations for prevention, testing, and early antiviral intervention.

Overview of COVID-19 Disease Severity in Children

• Most pediatric COVID‑19 infections are mild, a point that remains important for clinicians to communicate to families.
• However, a subset of children and adolescents face substantially higher risk for severe or critical disease, including complications such as myocarditis, thrombotic events, and post‑acute sequelae (long COVID).
• Identifying these high‑risk patients enables targeted prevention strategies – particularly vaccination – and timely initiation of antiviral therapy when indicated.
• A large systematic review and meta‑analysis (Aparicio C, et al. J Pediatric Infect Dis Soc. 2024) including nearly 200,000 pediatric patients provides foundational insight into risk distribution.
• Among previously healthy children without comorbidities, the absolute risk of severe or critical COVID‑19 is approximately 4%.
• While this percentage appears low, it becomes clinically meaningful during periods of high community transmission or localized outbreaks.
• More importantly, the analysis highlights specific demographic and clinical factors that markedly increase the likelihood of hospitalization, need for critical care, or development of complications.

Demographic Risk Factors

• Age is a significant determinant of disease severity. Infants younger than 1 year demonstrate an increased likelihood of severe outcomes, although the risk elevation is modest and not statistically significant for most infants.
• In contrast, neonates younger than 1 month show a substantially higher risk, with an odds ratio (OR) of 2.4 compared with older children.

Impact of Comorbidities

• Underlying medical conditions are the strongest predictors of severe pediatric COVID‑19. The meta‑analysis demonstrates that:
• One comorbidity increases the risk of severe disease approximately 4‑fold.
• Two or more comorbidities increase the risk nearly 10‑fold.
• Several categories of comorbidities are associated with particularly high risk of severe COVID-19:
• Cardiovascular disease, e.g. congenital heart disease, hypertension: OR 3.5 compared with patients without this comorbidity
• Neurologic disorders, e.g. seizure disorders, developmental disabilities, trisomy 21 (Down syndrome): OR 3.4
• Chronic gastrointestinal or kidney disease: OR 3.2 and 2.9, respectively
• Diabetes (type 1 and type 2) or obesity: OR 2.9 and 2.3, respectively
• Pulmonary conditions (excluding asthma): OR 2.9
• Interestingly, asthma alone does not appear to significantly increase the risk of severe COVID‑19 (OR 1.2), although vaccination of these patients should not be discouraged.
• Immunocompromised states, e.g. oncologic diagnosis: OR 2.2
• Collectively, these findings highlight a mismatch between disease burden and vaccination uptake. More than 45% of children in the USA aged 3–17 years have at least one chronic medical condition, yet only 15–20% have received updated COVID‑19 boosters in many regions. Closing this gap is a critical public health priority.

Risk Stratification Framework

• A practical approach to identifying high‑risk pediatric patients includes three major categories:

1. Conditions that increase risk for most respiratory viruses.

• Congenital heart disease
• Chronic lung disease
• Neurologic disorders
• Immunocompromised states

These children benefit from a holistic prevention strategy that includes both COVID‑19 and influenza vaccination.

1. Conditions that disproportionately increase risk for COVID‑19 severity.

• Obesity
• Type 1 diabetes

In particular, obesity is closely linked to inflammatory pathways central to COVID‑19 pathogenesis.

1. Miscellaneous risk factors

• Substance use disorders
• Smoking

These factors increase susceptibility to bacterial and respiratory infections broadly, including COVID‑19.

Practice Recommendations

• Three actionable practice recommendations emerge from current evidence:

1. Prioritize COVID-19 vaccination for children with medical comorbidities

• Shared decision‑making and anticipatory guidance are essential to support families in understanding the benefits of vaccination, particularly for high‑risk children.

1. Encourage respiratory viral testing in patients with comorbidities

• Early identification of COVID‑19 or influenza enables pathogen‑directed therapy. Although families may prefer to avoid clinical visits when children are ill, timely testing is crucial for guiding management.

1. Initiate antiviral therapy when indicated

• Early treatment reduces the likelihood of complications from COVID-19 in high‑risk pediatric patients.

Conclusions

Pediatric COVID‑19 remains a clinically significant respiratory infection for children with underlying medical conditions. Robust risk stratification, proactive vaccination efforts, timely diagnostic testing, and early antiviral intervention are essential components of care. As the landscape of COVID‑19 continues to evolve, ongoing attention to vulnerable pediatric populations will remain critical for reducing morbidity and improving outcomes.

Content is accurate as of the date of release on 6 January 2026.