The COVID-19 pandemic has continued to affect children, with the omicron surge resulting in many children requiring hospitalization, some in the intensive care unit.
Antivirals are one of the limited options for treatment of COVID-19 in the pediatric population. Following is an overview of three antivirals the Food and Drug Administration has granted emergency use authorization (EUA) for treatment in children.
Remdesivir is a prodrug that prevents viral replication of SARS-CoV-2. It inhibits the SARS-CoV-2 RNA-dependent RNA polymerase and acts as a barrier to further viral transcription. The RNA product is unable to proofread appropriately by the viral exonuclease, resulting in premature termination. The final RNA product is unable to continue in the viral replication sequence (Kokic G, et al. Nat Commun. 2021;12:279).
Remdesivir is approved under EUA for children weighing >3.5 kilograms (kg) with confirmed SARS-CoV-2 infection. It can be used within seven days of symptom onset in hospitalized children or those who are not hospitalized with COVID-19 and are deemed at high risk of progression to severe COVID-19 (https://www.fda.gov/media/137566/download).
Nirmatrelvir-ritonavir is a combination of two antivirals that are co-packaged for oral use. Nirmatrelvir inhibits replication of SARS-COV-2 by inhibiting the viral enzymes and processing of protein precursors. Ritonavir has no pharmacologic activity against SARS-CoV-2. Instead, it decreases the breakdown of nirmatrelvir and acts as a pharmaceutical enhancer, allowing nirmatrelvir to remain in the body for a longer period and at a higher plasma concentration.
Nirmatrelvir-ritonavir is approved under EUA for use within five days of symptom onset in children ages 12 years and older weighing >40 kg with confirmed SARS-CoV-2 infection and deemed at high risk of progression to severe COVID-19 (https://www.fda.gov/media/155050/download).
Although baricitinib is an immunomodulator, it is thought to have antiviral effects through interference with viral entry of SARS-CoV-2. Baricitinib inhibits the Janus kinase pathway, which reduces serum immunoglobulin G, M and A and C-reactive protein. Baricitinib specifically inhibits intracellular membrane proteins that are thought to play a role in receptor-mediated endocytosis of many viruses, including SARS-CoV-2. Baricitinib is approved under EUA for children 2 years and older who are hospitalized with severe COVID-19.
With continued implementation of quality research in the pediatric population, the status of these medications may change.
Dr. Stark is a member of the AAP Section on Pediatric Trainees. Dr. Greenberg is a member of the Section on Clinical Pharmacology and Therapeutics Executive Committee.
- AAP COVID-19 interim guidance: Management Strategies in Children and Adolescents with Mild to Moderate COVID-19
- FDA fact sheets for health care providers on emergency use authorization of Veklury, Paxlovid, and baricitinib