Key Clinical Summary: Preventing severe disease and sequelae of COVID-19

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 reviews current strategies to reduce the risk of severe disease and post‑acute sequelae in high‑risk children, outlining the role of vaccination, passive prophylaxis with monoclonal antibodies, and early therapeutic intervention. It examines key complications associated with pediatric COVID‑19 and highlights clinical considerations for antiviral and immunomodulatory treatment across outpatient and inpatient settings.

Prevention Strategies: Vaccination and Passive Prophylaxis

• Preventing severe COVID‑19 and its long‑term consequences remains a central goal in pediatric care.
• Vaccination is the primary preventive tool and is authorized for individuals 6 months of age and older.
• Vaccines remain most effective at preventing severe illness, hospitalization, and death, and have been administered globally in billions of doses with a strong safety profile.
• Current recommendations emphasize prioritizing vaccination for high‑risk groups and using shared decision‑making to weigh benefits and risks.
• For children who are moderately or severely immunocompromised and therefore unlikely to mount an adequate immune response to vaccination, pre‑exposure prophylaxis with monoclonal antibodies remains an important adjunct.
• Pemivibart is authorized for adults and children ≥12 years and ≥40 kg who meet immunocompromise criteria.
• It may be used alongside vaccination, with administration delayed at least 14 days after a COVID‑19 vaccine dose.
• Pemivibart is given as a 1‑hour intravenous infusion and may be repeated every 3 months if the patient remains at elevated risk.
• Data from the CANOPY study suggest that in significantly immunocompromised adults, pemivibart may reduce the risk of PCR‑confirmed symptomatic COVID‑19.
• Importantly, it retains activity against currently circulating variants, making it a valuable option for patients unable to rely on vaccine‑induced immunity.

Complications of COVID‑19 in Children

• COVID‑19 complications in children can be divided into acute severe disease and longer‑term sequelae.
• Severe disease is typically characterized by respiratory compromise, which can be mitigated through vaccination, pre‑exposure prophylaxis, and early initiation of antiviral or immunomodulatory therapy.
• Several complications warrant particular attention:
• Myopericarditis: Myopericarditis is a recognized complication of COVID‑19, especially in young adults. The risk is highest in the year following infection, with an estimated incidence of 1 in 5,000. Importantly, myocarditis after COVID‑19 infection occurs at least five times more frequently than after vaccination.
• Neurologic complications: COVID‑19 has been associated with febrile seizures in children. Some of these may overlap with or contribute to long COVID.
• Multisystem inflammatory syndrome (MIS‑C): MIS-C in children was a prominent early‑pandemic complication but is now rarely encountered. Broad population immunity and repeated exposures have dramatically reduced its incidence. Whether some current Kawasaki‑like presentations represent attenuated forms of MIS‑C remains under investigation.
• Long COVID: This remains the most common post‑acute complication. At least 25% of children may experience persistent symptoms such as chronic fatigue, deconditioning, cognitive difficulties (‘brain fog’), word‑finding challenges, or mood disturbances. These sequelae can significantly affect school performance, physical activity, and quality of life. Preventing infection and reducing disease severity through vaccination and early treatment may help reduce the risk of long COVID.

Treatment Considerations

• Most pediatric COVID‑19 cases are mild, and supportive care is sufficient for the majority. Fewer than 5% of pediatric infections progress to severe disease.
• However, early antiviral therapy is recommended for high‑risk outpatients, including those with diabetes, neurologic conditions, cardiac comorbidities, or significant pulmonary disease.
• Oral antiviral options are available for eligible adolescents, while intravenous therapy may be used in younger children or those requiring hospitalization.
• For hospitalized patients, treatment decisions depend on oxygen requirements:
• Low‑flow oxygen (nasal cannula): prioritize antiviral therapy
• Escalating oxygen needs: add dexamethasone or other immunomodulators
• Severe respiratory failure: consider additional agents such as IL‑6 inhibitors or JAK inhibitors

Conclusions

Preventing severe pediatric COVID‑19 and its sequelae requires a multifaceted strategy that includes vaccination, passive prophylaxis, early testing, and timely initiation of antiviral or immunomodulatory therapy. Vaccination remains the most effective tool for reducing severe disease and long‑term complications, and prophylaxis with monoclonal antibodies provides an important option for children unable to mount adequate vaccine responses. Identifying high‑risk children, particularly infants, those with multiple comorbidities, and those with immunocompromise, is essential for targeted prevention and management.

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