Evidence Based Strategies: Updates on the Management of COVID-19 Illness

Column Author:  Brianna Hafenstine, MD| Pediatric Resident PGY 3

Column Editor:  Kathleen J. Berg, MD, FAAP | Medical Director, Office of Evidence-Based Practice, Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine

From the onset of the coronavirus 2019 (COVID-19) pandemic through May 2023, nearly 15.6 million children tested positive for SARS-CoV-2.¹ This well-known illness can cause typical viral upper respiratory tract symptoms, including cough, shortness of breath, fevers, chills, sore throat, rhinorrhea and nasal congestion. Adults are more likely than children to have severe COVID-19 disease. However, research has also shown that children with comorbidities are at higher risk of developing severe disease than their healthy counterparts.^2,3 As pediatricians continue to see cases of COVID-19 disease with varying degrees of severity in children with varying comorbidities, Children’s Mercy’s Department of Evidence Based Practice along with content experts created a clinical pathway for management of COVID-19.⁴ This pathway brings together the management guidelines of the Infectious Diseases Society of America (IDSA),⁵ based mainly on adult data, and the limited pediatric COVID-19 research. The clinical pathway is an evidence-based tool for clinicians to use in the management of COVID-19 in both outpatient and inpatient settings.⁴ 

In the outpatient setting, supportive care is generally the mainstay of treatment, as most children are asymptomatic or have mild disease symptoms. However, it is important to identify children at higher risk of progressing to severe disease as they could be candidates for an oral medication consisting of nirmatrelvir and ritonavir, known as Paxlovid.⁵ Nirmatrelvir inhibits viral replication, while ritonavir increases the half-life and concentration of nirmatrelvir in the body. Children with any of the following factors, regardless of immunization status, are placed in the high-risk category, and Paxlovid can be considered.^2,4-6

To qualify for Paxlovid, patients must be at least 12 years old AND >40 kg and able to take the first dose within five days of symptom onset. Paxlovid should be given twice daily for five days. While you can renally dose Paxlovid, it is not recommended in those with eGFR <30 mL/min. Finally, it is important to review drug-drug interactions, including medications involving the CYP3A pathway, before prescribing the drug to patients.⁷ For patients at high risk who do not meet criteria for Paxlovid, evidence on treatment options is very limited. To date, use of remdesivir for children <12 years of age in the outpatient setting has not been researched, and evidence can only be extrapolated from adult and/or inpatient studies.

From an inpatient perspective, the clinical pathway recommends stratifying patients with COVID-19 based on their severity of illness by the level of respiratory support required.⁵ Patients not requiring oxygen (or those not requiring more than their baseline oxygen needs) are categorized as having mild to moderate illness. For these patients, it is again necessary to know if they are at higher risk for progression to severe illness, and if so, Paxlovid should be considered as detailed above. For a patient with severe illness who requires supplemental oxygen via nasal cannula or high-flow nasal cannula but does not require intensive care, it is recommended to give oral or intravenous (IV) dexamethasone for 10 days or until discharge and IV remdesivir for five days or until discharge. Remdesivir is approved for patients >28 days of age and >3 kg and should be started within seven days of symptom onset. A caveat not addressed in the IDSA guideline is that of bronchiolitis due to COVID-19. For an otherwise healthy patient who is <2 years old with presentation consistent with bronchiolitis, it may be appropriate to treat with supportive care alone even if they require supplemental oxygen. Finally, for those with critical illness (requiring intensive care along with high-flow nasal cannula, non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation), dexamethasone is recommended, and tocilizumab should be considered. For patients with severe and critical illness, anticoagulation should be considered if a patient is at high risk for venous thromboembolism.^4,5

As in the outpatient setting, it is important to highlight that evidence on remdesivir for children in the inpatient setting is limited. The IDSA recommends its use for hospitalized patients with severe disease or high risk for progression to severe disease.⁵ However, in pediatric studies evaluating the efficacy and safety of remdesivir, study arms differed significantly by disease severity, comorbidities, number of days of remdesivir treatment, and concurrent treatments.⁸ Without matched controls, neither benefits nor adverse events can be clearly attributed to remdesivir. For hospitalized patients with mild to moderate illness with higher risk for progression to severe disease and hospitalized patients under 2 years old with bronchiolitis, there are no pediatric-specific recommendations for remdesivir treatment. For these cases, IV remdesivir should be considered on a case-by-case basis with shared decision-making to consider feasibility, patient comfort, cost, and values of the patient and family.⁴

Understanding the evidence, and limitations of the evidence, on the management of COVID-19 can help clinicians identify patients who could benefit from medications for SARS-CoV-2 in addition to supportive care. More research must be conducted to further understand COVID-19 treatment in children, but the Children’s Mercy clinical pathway utilizes the current evidence to provide a helpful tool for clinicians. For further details, please visit COVID-19 | Children's Mercy Kansas City.

References:

1. American Academy of Pediatrics. Children and COVID-19: state-level data report. American Academy of Pediatrics. Updated March 2, 2023. Accessed April 18, 2025.
2. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/
3. Graff K, Smith C, Silveira L, et al. Risk factors for severe COVID-19 in Children. Pediatr Infect Dis J. 2021;40(4):e137-e145. doi:10.1097/INF.0000000000003043
4. Woodruff RC, Campbell AP, Taylor CA, et al. Risk factors for severe COVID-19 in children. Pediatrics. 2022;149(1):e2021053418. doi:10.1542/peds.2021-053418
5. Children’s Mercy Kansas City. Department of Evidence Based Practice. COVID-19 Clinical Pathway Committee. COVID-19 Clinical Pathway. Accessed April 18, 2025.
6. https://www.childrensmercy.org/health-care-providers/evidence-based-practice/cpgs-cpms-and-eras-pathways/covid-19/
7. Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 (September 2022). Clin Infect Dis. 2024;78(7):e250-e349. doi:10.1093/cid/ciac724
8. S. Centers for Disease Control & Prevention. COVID-19. Clinical course: progression, management, and treatment. Accessed April, 18, 2025. https://www.cdc.gov/covid/hcp/clinical-care/management-and-treatment.html
9. Lemaitre F, Grégoire M, Monchaud C, et al. Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: guidelines from the French Society of Pharmacology and Therapeutics (SFPT). Therapie. 2022;77(5):509-521. doi:10.1016/j.therap.2022.03.005
10. Children’s Mercy Kansas City. Department of Evidence Based Practice. COVID-19 Clinical Pathway: Evidence for Treatment with Remdesivir in Children with COVID-19. Accessed April 18, 2025. https://www.childrensmercy.org/siteassets/media-documents-for-depts-section/documents-for-health-care-providers/block-clinical-practice-guidelines/mobileview/covid-19-in-children-evidence-for-treatment-with-remdesivir.pdf