Key Clinical Summary: Therapeutic Decision-Making for Children with COVID

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 approaches to managing high‑risk children and adolescents with COVID‑19, outlining principles of risk assessment, indications for antiviral and immunomodulatory therapy, and practical considerations for outpatient and inpatient treatment relevant to optimizing outcomes in vulnerable pediatric populations.

Clinical Context and Risk Assessment

• Although the acute phase of the pandemic has passed, COVID‑19 remains a clinically significant respiratory pathogen for many children, particularly those with underlying medical conditions. Effective management requires early identification of patients at elevated risk for complications.
• A case example illustrates this approach:
• A 14‑year‑old with type 1 diabetes and autism presents to the emergency room with fever, cough, and increased work of breathing. Fever has been present for 4 days and symptoms are worsening.
• Oxygen saturations are 93% on room air and the respiratory rate is 25.
• She is placed on nasal cannula O2 (2L) and admitted for observation.
• Now consider:
• Is she at high risk?
• Does she need antivirals?
• Does she need immunomodulation?
• Both type 1 diabetes and neurologic conditions such as autism are associated with increased risk of severe respiratory disease.
• Diabetes confers approximately a 3‑fold increase in the risk of severe COVID‑19, while neurologic disorders elevate risk more than 3-fold.
• These factors collectively support classifying such a patient as high risk for complications.

Therapeutic Options: Antiviral Agents

Nirmatrelvir–Ritonavir

• Indicated for patients ≥12 years old and ≥40 kg.
• Administered orally for 5 days.
• Most effective when initiated within 5 days of symptom onset, typically using fever onset as a reference point.
• Weight criteria are particularly relevant for children with chronic gastrointestinal disease or failure to thrive.

Remdesivir

• Administered intravenously for 3 days.
• May be initiated within 7 days of symptom onset, reflecting its utility during the early inflammatory phase when viral replication still contributes to disease progression.

Immunomodulatory Therapies

Dexamethasone

• Widely used and readily available.
• Dosed on a mg/kg basis for 5–10 days.
• May be substituted with prednisone when necessary.

Baricitinib

• A Janus kinase (JAK) inhibitor targeting upstream inflammatory pathways.
• Used primarily in severe disease or when corticosteroids are contraindicated.

Tocilizumab

• An IL‑6 inhibitor targeting a key pro‑inflammatory cytokine.
• Reserved for severe disease or cases where corticosteroids cannot be safely administered.

Outpatient Treatment Framework

• Outpatient antiviral or immunomodulatory therapy is limited to specific high‑risk groups. Treatment should be considered when:
• The child has moderate or severe immunocompromise, including cancer, untreated HIV, or chronic steroid use.

OR

• There is an underlying condition that increases risk, and the child is not up to date on vaccination and has not had COVID‑19 infection within the previous 4 months.

AND

• The child is <1 or ≥12 years old, and/or
• The child has ≥2 underlying medical conditions, and /or
• The child has ≥1 severe or poorly controlled condition(s).
• These criteria emphasize the importance of early identification and timely initiation of therapy in the outpatient setting.

Inpatient Treatment Framework

• If there is a new/increased oxygen demand, recommendations are based on route of supplemental O2 delivery
• Nasal cannula: Start remdesivir; if no improvement in 24–48 hours, add dexamethasone
• High-flow nasal cannula or greater: Start dexamethasone and remdesivir
• Mechanical ventilation/Extracorporeal Membrane Oxygenation(ECMO): Start dexamethasone; if no improvement add baricitinib or tocilizumab
• This tiered approach reflects the evolving balance between viral replication and host‑driven inflammation across the disease course.

Key Principles: Know, Test, Treat

1. Know who is at highest risk: Infants <1 month; children with ≥2 comorbidities; children with ≥1 poorly controlled or unstable chronic conditions; immunocompromised patients
2. Test appropriately: SARS‑CoV‑2 testing should be performed in the presence of appropriate symptoms, including fever, respiratory symptoms, or sore throat.
3. Treat based on risk and severity: Use antivirals, immunomodulators, or both depending on disease stage and clinical status.

Conclusions

Management of high‑risk pediatric COVID‑19 requires careful risk stratification, timely diagnostic testing, and judicious use of antiviral and immunomodulatory therapies. A structured, severity‑based approach ensures that children most vulnerable to complications receive appropriate and timely treatment, improving clinical outcomes in this important population.

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