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Clinical Management of Children Summary

Last Updated: August 22, 2023

Data from the Centers for Disease Control and Prevention demonstrate that SARS-CoV-2 infection and severe disease and death due to COVID-19 occur less often in children than in adults.1-4 Although only a small percentage of children with COVID-19 will require medical attention, the percentage of intensive care unit admissions among hospitalized children is comparable to that for hospitalized adults with COVID-19.5-16

Observational studies and meta-analyses have found that children with certain comorbidities have a higher risk of severe COVID-19. These comorbidities include cardiac disease, neurologic disorders, prematurity (in young infants), diabetes, obesity (particularly severe obesity), chronic lung disease, feeding tube dependence, and immunocompromised status.17-20 Demographic factors, such as age (<1 year and 10–14 years)21 and non-White race/ethnicity,12,22-24 have also been associated with severe disease. However, many studies did not assess the relative severity of underlying medical conditions in children with severe COVID-19.

In general, COVID-19 has similar clinical manifestations and disease stages in children and adults, including an early phase driven by viral replication and a late phase that appears to be driven by a dysregulated immune/inflammatory response to SARS-CoV-2 that leads to tissue damage. Respiratory complications in young children that can occur during the early clinical phase include croup and bronchiolitis. In addition, a small number of children who have recovered from acute SARS-CoV-2 infection develop multisystem inflammatory syndrome in children (MIS-C) 2 to 6 weeks after infection. MIS-C is a postinfectious inflammatory condition that can lead to severe organ dysfunction.

The published guidance on treating COVID-19 in children has been mostly extrapolated from recommendations for adults with COVID-19, recommendations for children with other viral infections, and expert opinion.25-27 Applying adult data from COVID-19 trials to children is a unique challenge because most children experience a mild course of illness with COVID-19. Relative to adults, children with COVID-19 have substantially lower mortality and less need for hospitalization. Because of these differences in epidemiology and disease severity, the effect sizes for children are likely to be smaller than those observed in adults; therefore, to produce a beneficial outcome, the number needed to treat is higher. Collectively, these factors influence the risk versus benefit balance for pharmacologic therapies in children.

In the absence of sufficient clinical trial data on the treatment of children with COVID-19, the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for the therapeutic management of children are based largely on safety and efficacy data from clinical trials in adults, the child’s risk of disease progression, and expert opinion. In general, the data from clinical trials in adults are most applicable when treating older children with severe COVID-19 and predominantly lower respiratory tract disease. It is challenging to develop recommendations for children with SARS-CoV-2 infection who present with clinical syndromes that are also associated with other respiratory viruses (e.g., bronchiolitis, croup, asthma) using data from clinical trials in adults. There is no evidence to suggest that these syndromes should be managed differently when caused by SARS-CoV-2 infection. Clinical judgment is needed when applying recommendations for treating adults with these clinical syndromes to children, particularly young children.

The Panel’s recommendations for the management of children with COVID-19 or MIS-C are summarized in the tables below. Table 3a provides recommendations for the therapeutic management of nonhospitalized children with COVID-19. The Panel’s recommendations are stratified by age (per the Food and Drug Administration Emergency Use Authorizations) and risk level. See Therapeutic Management of Nonhospitalized Children With COVID-19 for more information. Table 3b includes a framework to help clinicians evaluate the risk for severe COVID-19 based on patient conditions and COVID-19 vaccination status.

The recommendations for hospitalized children in Table 3c are stratified by disease severity. See Therapeutic Management of Hospitalized Children With COVID-19 for more information. Table 3d summarizes the recommendations for the therapeutic management of MIS-C. For the rationale behind these recommendations and supporting data, see Therapeutic Management of Hospitalized Children With MIS-C, Plus a Discussion on MIS-A.

Table 3a. Therapeutic Management of Nonhospitalized Children With COVID-19

Symptomatic, Regardless of Risk Factors

OPEN  
Aged 12–17 Years
  • Provide supportive care (AIII).
Aged <12 Years
  • Provide supportive care (AIII).

High Riska,b

OPEN  
Aged 12–17 Years
  • Use 1 of the following options (listed in order of preference):c
    • Ritonavir-boosted nirmatrelvir (Paxlovid) within 5 days of symptom onset (BIII)
    • Remdesivir within 7 days of symptom onset (CIII)
Aged <12 Years
  • Ritonavir-boosted nirmatrelvir is not authorized by the FDA for use in children aged <12 years.
  • There is insufficient evidence to recommend either for or against the routine use of remdesivir. Consider treatment based on age and other risk factors.
  1. Molnupiravir is not authorized by the FDA for use in children aged <18 years and should not be used.
  2. See Table 3b for the Panel’s framework for assessing the risk of progression to severe COVID-19 based on patient conditions and COVID-19 vaccination status.
  3. Initiate treatment as soon as possible after symptom onset.

Intermediate Riskb,d

OPEN  
Aged 12–17 Years
  • There is insufficient evidence to recommend either for or against the use of any antiviral therapy. Consider treatment based on age and other risk factors.
Aged <12 Years
  • There is insufficient evidence to recommend either for or against the routine use of remdesivir.
  1. See Table 3b for the Panel’s framework for assessing the risk of progression to severe COVID-19 based on patient conditions and COVID-19 vaccination status.
  1. The relative risk of severe COVID-19 for intermediate-risk patients is lower than the risk for high-risk patients but higher than the risk for low-risk patients.

Low Riskb,e

OPEN  
Aged 12–17 Years
  • Manage with supportive care alone (BIII).
Aged <12 Years
  • Manage with supportive care alone (BIII).
  1. See Table 3b for the Panel’s framework for assessing the risk of progression to severe COVID-19 based on patient conditions and COVID-19 vaccination status.
  1. Low-risk patients include those with comorbid conditions that have a weak or unknown association with severe COVID-19. Patients with no comorbidities are included in this group.

Each recommendation in the Guidelines receives a rating for the strength of the recommendation (A, B, or C) and a rating for the evidence that supports it (I, IIa, IIb, or III). See Guidelines Development for more information.

Key: FDA = Food and Drug Administration; the Panel = the COVID-19 Treatment Guidelines Panel

Table 3b. The Panel’s Framework for Assessing the Risk of Progression to Severe COVID-19 Based on Patient Conditions and COVID-19 Vaccination Status
Table 3b. The Panel’s Framework for Assessing the Risk of Progression to Severe COVID-19 Based on Patient Conditions and COVID-19 Vaccination Status
Click here to view this table.

Table 3c. Therapeutic Management of Hospitalized Children With COVID-19

Hospitalized for COVID-19

OPEN  

For children aged ≥12 years admitted for COVID-19, use prophylactic anticoagulation unless contraindicated (BIII).a

  1. Weighing the risk factors for thrombosis and bleeding, some Panel members would use prophylactic anticoagulation for children aged <12 years who are hospitalized for COVID-19.

Does Not Require Supplemental Oxygen

OPEN  

For children admitted for COVID-19 who are at the highest risk of progression to severe COVID-19,b consider using remdesivirc for children aged 12–17 years (CIII). There is insufficient evidence for using remdesivir in children aged 28 days to <12 years.

For children admitted for reasons other than COVID-19 who have mild to moderate COVID-19 and are at the highest risk of progression,b refer to Therapeutic Management of Nonhospitalized Children With COVID-19.

  1. For example, for children who are severely immunocompromised regardless of COVID-19 vaccination status and those who are unvaccinated and have additional risk factors for progression (see Therapeutic Management of Nonhospitalized Children With COVID-19).
  2. The clinical benefit of remdesivir is greatest if it is initiated within 10 days of symptom onset. Remdesivir should be given for 5 days or until hospital discharge, whichever comes first.

Requires Conventional Oxygend

OPEN  
Use 1 of the following options:
  • Remdesivirc (BIII)
  • Dexamethasone plus remdesivirc for children with increasing oxygen needs, particularly adolescents (BIII)
  1. The clinical benefit of remdesivir is greatest if it is initiated within 10 days of symptom onset. Remdesivir should be given for 5 days or until hospital discharge, whichever comes first.
  2. Conventional oxygen refers to oxygen supplementation that is not high-flow oxygen, NIV, MV, or ECMO.

Requires Oxygen Through High-Flow Device or NIVe

OPEN  
Use 1 of the following options:
  • Dexamethasone (BIII)
  • Dexamethasone plus remdesivirc (BIII)

For children who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone, baricitinibf or tocilizumab can be considered for children aged 12–17 years (BIII) and for children aged 2–11 years (CIII).

  1. The clinical benefit of remdesivir is greatest if it is initiated within 10 days of symptom onset. Remdesivir should be given for 5 days or until hospital discharge, whichever comes first.
  1. Patients who are receiving NIV or MV at baseline and require a substantial increase in baseline support should be treated per the recommendations for patients requiring new NIV or MV.
  2. Tofacitinib is an alternative if baricitinib is not available (BIII).

Requires MV or ECMOg

OPEN  

Dexamethasoneg (AIII)

For children who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone, baricitinibf or tocilizumab may be considered for children aged 12–17 years (BIII) and for children aged 2–11 years (CIII).

  1. Tofacitinib is an alternative if baricitinib is not available (BIII).
  2. For children who started receiving remdesivir before admission to the ICU, the remdesivir should be continued to complete the treatment course.

Each recommendation in the Guidelines receives a rating for the strength of the recommendation (A, B, or C) and a rating for the evidence that supports it (I, IIa, IIb, or III). See Guidelines Development for more information.

Key: ECMO = extracorporeal membrane oxygenation; ICU = intensive care unit; MV = mechanical ventilation; NIV = noninvasive ventilation; the Panel = the COVID-19 Treatment Guidelines Panel 

Table 3d. Therapeutic Management of Hospitalized Pediatric Patients With MIS-C

MIS-C

OPEN  

Initial treatment for MIS-C includes both immunomodulatory and antithrombotic therapy.

Initial Immunomodulatory Therapy

  • IVIG 2 g/kg IBW (up to a maximum total dose of 100 g) IV plus low to moderate dose methylprednisolone (1–2 mg/kg/day) IVa or another glucocorticoid at an equivalent dosea (AIIb).
  • Glucocorticoid monotherapy, only if IVIG is unavailable or contraindicated (BIIa).
  • IVIG monotherapy, only if glucocorticoids are contraindicated (BIIb).

Intensification Immunomodulatory Therapy

  • Intensification therapy is recommended for children with refractory MIS-C who do not improve within 24 hours of receiving initial immunomodulatory therapy (AIII). One of the following can be used (listed in alphabetical order):
    • High-dose anakinra 5–10 mg/kg IV or SUBQ once daily (BIIb)
    • Higher-dose glucocorticoid (e.g., methylprednisolone 10–30 mg/kg/day IV or equivalent glucocorticoid) (BIIb)b
    • Infliximabc 5–10 mg/kg IV for 1 dose (BIIb)

Antithrombotic Therapy

  • Low-dose aspirin (3–5 mg/kg/day, up to maximum dose of 81 mg/day) PO for all patients without risk factors for bleeding (AIII), AND
  • Anticoagulation for patients who fall under 1 of the following clinical scenarios:
    • Therapeutic anticoagulation for patients with large CAAs according to the American Heart Association guidelines for Kawasaki disease (AIII).
    • Therapeutic anticoagulation for patients with moderate to severe LV dysfunction who have no risk factors for bleeding (AIII).
    • For patients with MIS-C who do not have large CAAs or moderate to severe LV dysfunction, consider prophylactic or therapeutic anticoagulation on an individual basis, taking into consideration risk factors for thrombosis and bleeding. See Table 3e for additional information.
  1. Duration of therapy may vary. For more information, see Therapeutic Management of Hospitalized Children With MIS-C, Plus a Discussion on MIS-A.
  2. In certain patients with severe illness, intensification therapy may include dual therapy with higher-dose glucocorticoids and infliximab or anakinra. Anakinra and infliximab should not be given in combination.
  3. Infliximab should not be used in patients with macrophage activation syndrome.

Each recommendation in the Guidelines receives a rating for the strength of the recommendation (A, B, or C) and a rating for the evidence that supports it (I, IIa, IIb, or III). See Guidelines Development for more information.

Key: CAA = coronary artery aneurysm; IBW = ideal body weight; IV = intravenous; IVIG = intravenous immunoglobulin; LV = left ventricular; MIS-C = multisystem inflammatory syndrome in children; PO = oral; SUBQ = subcutaneously

References

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  2. Centers for Disease Control and Prevention. Provisional COVID-19 deaths: focus on ages 0–18 years. 2023. Available at: https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-Focus-on-Ages-0-18-Yea/nr4s-juj3. Accessed June 23, 2023.
  3. Centers for Disease Control and Prevention. Demographic trends of COVID-19 cases and deaths in the US reported to CDC. 2023. Available at: https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed June 23, 2023.
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