Last Updated

10/31/2022

General pediatricians, pediatric medical subspecialists and pediatric surgical specialists have a crucial role in providing frontline medical care to children and adolescents during the ongoing COVID-19 pandemic. As of October 13, 2022, over 14.8 million children and adolescents have had laboratory-confirmed SARS-CoV-2 infection, representing 18.4% of all reported COVID-19 cases in the United States.1,2

Changes in SARS-CoV-2 epidemiology, including the emergence of distinct SARS-CoV-2 variants and subvariants, have altered the landscape of options for SARS-CoV-2 directed therapies. These data are important in the management of high-risk patients with COVID-19, since the activity of some SARS-CoV-2 monoclonal antibodies (mAb) will vary depending on the circulating SARS-CoV-2 subvariant.5

The US Food and Drug Administration (FDA) has approved and issued Emergency Use Authorizations (EUAs) for COVID-19 directed therapies in non-hospitalized, high-risk individuals in outpatient settings, including (1) updates on SARS-CoV-2 mAb6 for (a) the treatment of mild to moderate COVID-197,8 and (b) preexposure prophylaxis9 (Table 1) and (2) early use of antiviral therapies.10 Given dominant SARS-CoV-2 variants circulating in the United States, no COVID-19 mAb or antivirals are authorized for use as postexposure prophylaxis.

This interim guidance briefly summarizes currently available recommendations for the outpatient management of mild to moderate COVID-19 in children and adolescents at highest risk for disease progression and is also intended to help navigate management challenges and considerations, while acknowledging the following ongoing major limitations:

  1. These therapies have been authorized for individuals at highest risk for severe COVID-19 and disease progression, including those who may not be eligible for COVID-19 vaccination, have an underlying medical condition or are receiving therapies that are known to result in a poor antibody response to vaccination. Current evidence remains limited but is evolving regarding which underlying medical conditions in children definitively associate with higher risk for severe COVID-19 or disease progression.
  2. There continues to be a paucity of pediatric-specific data regarding the safety, efficacy and pharmacokinetics of mAb products and oral antiviral medications across all pediatric age groups.
  3. Some agents may be in short supply locally, potentially limiting their use.11 Refer to these updates regarding the federal response and allocation of COVID-19 therapeutics.

The National Institutes of Health (NIH) COVID-19 Treatment Guideline Panel provides a framework for assessing risk of progression to severe COVID-19 based on underlying medical conditions, vaccination status, illness severity and age.8 Notably, given lack of pediatric clinical trial data, the recommendations for the therapeutic management of COVID-19 in non-hospitalized children are based primarily on safety and efficacy data from clinical trials in adults, and thus, the quality of the evidence is based on expert opinion. The NIH Panel’s current treatment recommendations for mild to moderate COVID-19 in symptomatic non-hospitalized children at highest risk for progression to severe COVID-19 include12:

  • Preferred therapies: Paxlovid or remdesivir
  • There is insufficient evidence to recommend either for or against the use of alternative therapies including bebtelovimab or molnupiravir (latter in individuals ≥18 years of age). The NIH Panel notes that bebtelovimab or molnupiravir may be used as an alternative therapy when preferred therapies are unavailable, not feasible, or not clinically appropriate in nonhospitalized adults who meet EUA criteria.

Providers will need to continue to evaluate multiple factors when assessing potential risks and benefits of therapy and selecting possible treatment options for an individual patient, including and not limited to the clinical efficacy of agents, availability of the treatment in their geographic area, feasibility of administering the medication, local and regional SARS-CoV-2 epidemiology including variant and subvariant types, host-specific factors including concurrent medical conditions and possibility of drug-drug interactions and available safety data for these medications in children. Providers should refer to the risk assessment framework to identify children at highest risk for severe COVID-19 and who may benefit from receiving COVID-19-directed treatment.8

In the context of SARS-CoV-2 Omicron variant circulation in most communities, which FDA authorized SARS-CoV-2 mAb may be used in children?

New variants of SARS-CoV-2 are expected to continue to emerge. On the basis of currently available data, the choice of mAb in eligible patients to treat mild to moderate COVID-19 or as pre-exposure prophylaxis depends on the local predominant circulating SARS-CoV-2 subvariant.5 Bebtelovimab7,13 and tixagevimab copackaged with cilgavimab (Evusheld)14,15 have retained neutralizing activity against SARS-CoV-2 Omicron subvariants currently circulating.

There is insufficient evidence for the NIH Panel to recommend either for or against mAb products in children with COVID-19; efficacy data in adults suggest that these products may be considered in children who meet EUA criteria.10 At this time, only high-risk children ≥12 years of age and weighing ≥40 kg would be eligible to receive bebtelovimab for the treatment of mild to moderate COVID-19 or tixagevimab and cilgavimab (Evusheld) for preexposure prophylaxis of COVID-19 as outpatients, if they meet the following criteria:

Bebtelovimab for COVID-19 treatment8

  • Nonhospitalized patient ≥12 years of age and weighing ≥40 kg, and
  • Laboratory-confirmed SARS-CoV-2 infection, and
  • Mild to moderate16,17 COVID-19, and
  • Within 7 days of symptom onset, and
  • High risk for progressing to severe COVID-19 and/or hospitalization

mAb therapies are NOT authorized for use in:

  • Patients hospitalized for COVID-19; or
  • Patients who require oxygen therapy for COVID-19; or
  • Patients who require an increase in baseline oxygen flow rate in those already receiving chronic oxygen therapy for other, non–COVID-19 related, underlying conditions

Tixagevimab and cilgavimab (Evusheld) for COVID-19 preexposure prophylaxis15,18

  • Child/adolescent ≥12 years of age and weighing ≥40 kg, and
  • No SARS-CoV-2 infection or exposure: Not known to be currently infected with SARS-CoV-2 or had a known recent exposure to an individual infected with SARS-CoV-2, and
  • Moderate or severe immunocompromise from an underlying condition or medication that does not allow for an adequate serologic immune response to COVID-19 vaccination or in whom vaccination is medically contraindicated. Examples of conditions leading to moderate or severe immunosuppressiona include:
    • Receipt of a hematopoietic cell transplantation in the previous 2 years and lack of immune reconstitution or taking immunosuppressive medications
    • Receipt of chimeric antigen receptor (CAR) T-cell therapies in the previous 2 years
    • Known underlying primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome)
    • Untreated or advanced HIV infection (eg, history of having an AIDS-defining illness without immune reconstitution, CD4+ T-lymphocyte count <200/mm3)
    • Receiving active chemotherapy for underlying hematologic malignancies or solid tumors
    • Receipt of a solid organ transplant within the last 3 months and receiving immunosuppressive medications leading to moderate/severe immunocompromisea
    • Actively receiving treatment with immunosuppressive medications leading to moderate/severe immunocompromisec
  • Refer to Table 4 for tixagevimab and cilgavimab (Evusheld) administration information.
    • On February 24, 2022, the FDA revised the Evusheld EUA to authorize a higher dose, which based on available data may be more effective in preventing COVID-19 caused by circulating SARS-CoV-2 Omicron subvariants.19
      • Patients who have already received Evusheld at the previously authorized dosing (tixagevimab 150 mg and cilgavimab 150 mg) should receive an additional dose of tixagevimab 150 mg and cilgavimab 150 mg as soon as possible.
      • Eligible patients who have not previously received Evusheld should receive an initial authorized dose of tixagevimab 300 mg and cilgavimab 300 mg.
      • The efficacy and duration of mAbsagainst different and emerging SARS-CoV-2 variants and subvariants continues to be monitoredcurrently15,19 Nonclinical and PK modeling data suggest that Evusheld (300 mg/300 mg dosing) retains activity against variants currently circulating in the US (BA.2, BA.2.12.1, BA.4, BA.5) for 6 months. As such, repeat dosing every six months in at risk, eligible individuals is recommended.20
    • In eligible, high-risk children who recently received their COVID-19 mRNA vaccine, Evusheld should be given at least 2 weeks after their last COVID-19 vaccine dose.

Which children and adolescents are considered “high risk” and may qualify for outpatient treatment with SARS-CoV-2 monoclonal antibodies?

Data from randomized studies demonstrate that timely outpatient SARS-CoV-2 mAb therapy reduced the risk for hospitalization and death in at risk adults with COVID-19.21,22 Use of SARS-CoV-2 mAb for all indications remains investigational in children and adolescents. Lack of proven identifiable risk factors and lack of robust safety and efficacy data across all pediatric age groups preclude the routine use of mAb in all children and adolescents with COVID-19. Instead, an individual risk/benefit assessment should be performed when considering mAb for a child/adolescent who is at high risk for COVID-19 progression or disease severity.8,23-30 Changes in SARS-CoV-2 epidemiology and FDA EUA criteria allow mAb use in children ≥12 years of age and weighing ≥40 kg.

Strong or consistent criteria in the FDA EUA for SARS-CoV-2 mAb associated with high risk for severe COVID-19 include8,31:

  • Obesity, body mass index (BMI) ≥95th percentile for age and gender based on CDC growth charts, especially severe obesity (defined as BMI ≥120% of 95th percentile for age); 
  • Immunosuppressive disease or receipt of immunosuppressive therapies resulting in moderate or severe immunocompromisec;
  • Neurodevelopmental disorders (eg, cerebral palsy, trisomy 21) that result in impaired airway clearance; 
  • A medical-related technological dependence that is not related to COVID-19 (eg, tracheostomy, positive pressure ventilation, gastrostomy); 
  • Severe congenital or acquired heart disease; 
  • Severe chronic lung disease (eg, interstitial lung disease); severe asthma or other chronic respiratory disease that requires daily medication for control;
  • Multiple moderate to severe chronic diseases;
  • Pregnancy

Variables in the FDA EUA for SARS-CoV-2 mAb with moderate or inconsistent association with progression to severe COVID-19 in children:

  • Sickle cell disease; 
  • Diabetes (poorly controlled);
  • Chronic kidney disease;
  • Chronic liver disease (eg, cirrhosis, autoimmune hepatitis);
  • Non-severe cardiac, neurologic, or metabolic disease
  • Overweight;
  • Age <1 year
    • The majority of infants have mild, uncomplicated SARS-CoV-2 infection. Published case report data suggest that young infants, particularly those <90 days of age, are hospitalized more frequently; however, the indication for hospitalization may be confounded by need for evaluation of fever in these infants who otherwise have mild COVID-19 symptoms and good outcomes.32-35
    • Data evaluating risk factors for severe COVID-19 in young infants, in whom severity is defined by requiring admission to the intensive care unit or mechanical ventilation, have identified prematurity (gestational age <37 weeks) as a risk factor for severe COVID-19.26,28,36

Routine SARS-CoV-2 mAb therapies are not indicated for children/adolescents with COVID-19 at low risk for progression or hospitalization.

What adverse reactions have been reported after SARS-CoV-2 mAb therapies?

  • Local injection site reactions are the most frequently reported events (4%-12%). Infusion-related reactions, including fever, chills, shortness of breath, dizziness, abdominal pain, nausea, vomiting and flushing and pruritus, have been reported to occur during and up to 24 hours after administration. Serious hypersensitivity reactions, including anaphylaxis, may also occur.37
  • Pediatricians, pediatric medical specialists and pediatric surgical specialists should report all medication errors and serious adverse reactions potentially related to mAb to the FDA MedWatch Adverse Event Reporting program or by calling 1-800-FDA-1088 to request a reporting form.

[H3] What are additional considerations for children receiving SARS-CoV-2 mAb?

  • Despite receiving SARS-CoV-2 mAb therapy, clinical worsening of COVID-19 has been reported and may include fever, hypoxia or increased respiratory distress, dysrhythmias and altered mental status. Pediatricians, pediatric medical subspecialists and pediatric surgical specialists should advise parents/caregivers on how to monitor for clinical worsening, occurring most frequently in the first 7 to 10 days after symptom onset, and provide further instructions on when to seek emergency medical attention.
  • Children/adolescents who receive mAb for treatment or as postexposure prophylaxis should continue to isolate or take precautions (ie, wear a mask for 10 days and test at least 5 days after last exposure) and adhere to public health department policies and local recommendations for discontinuing isolation and precautions. See CDC recommendations on Isolation and Precautions.
  • Receipt of mAb does not preclude the need to continue to follow preventive measures, including wearing an appropriately fitted mask in children and adolescents ≥2 years of age, physical distancing and performing hand hygiene.
  • Neither acute SARS-CoV-2 infection nor treatment with mAb are substitutes for COVID-19 vaccination. Eligible children ≥6 months of age and their household contacts should receive COVID-19 vaccine when available to them. After SARS-CoV-2 infection, COVID-19 vaccination can be provided once symptoms resolve and the recommended isolation period has ended. Individuals who have received COVID-19 mAb for treatment or preexposure prophylaxis can receive their COVID-19 vaccine at any time.38 In individuals who have received COVID-19 vaccines, administration of Evusheld should be deferred for at least 2 weeks after vaccination.39

Are there precautions my practice should take when administering mAb?

  • Pediatricians, pediatric medical subspecialists and pediatric surgical specialists are encouraged to partner with their local pediatric hospitals, pediatric infectious disease specialists and health departments to inquire about the availability of mAb therapies, receive guidance on recommended mAb depending on local SARS-CoV-2 epidemiology and circulating variants and help to establish a reliable process for safe and timely administration of SARS-CoV-2 mAb to eligible patients.
  • In an effort to reduce COVID-19-related health care resource burden on hospitals, some facilities (eg, infusion centers, urgent care centers), medical practices and home health companies may be equipped and able to provide SARS-CoV-2 mAb; these sites are required to follow quality standards and clinically monitor patients for at least 1 hour after therapy, including having a reaction management kit, providing basic life support and activating emergency medical services, if needed.40-42
  • mAb should only be administered in settings in which health care clinicians have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. It may be necessary for pediatricians, pediatric medical subspecialists and pediatric surgical specialists to collaborate and to coordinate with community health care settings to provide mAb therapy. In addition, patients should be clinically monitored during administration and observed for at least 1 hour following administration.
  • Additional resources for health care professions administering mAb can be found here.
  • Information regarding availability and access to SARS-CoV-2 mAb therapies by location are available at: COVID-19 Therapeutics Locator.
  • Information regarding coding and payment for SARS-CoV-2 mAb therapies can be found here.

What are additional non-mAb therapies available to treat or prevent the progression of mild to moderate COVID-19 in children and adolescents?

  • The early use of intravenous (IV) remdesivir43 and oral antiviral medications (Paxlovid51 and molnupiravir50) have been evaluated in controlled clinical trials among non-hospitalized, high-risk individuals with mild to moderate COVID-19 and found to improve COVID-19 outcomes including disease progression, hospitalization and death. Current NIH recommendations favor the use of Paxlovid or remdesivir for mild to moderate COVID-19 in high-risk outpatients; alternative therapies, including bebtelovimab and molnupiravir may be considered if preferred options are not available or clinically cannot be used. Table 3 summarizes the currently authorized options.
  • Intravenous (IV) remdesivir: Remdesivir is the only drug approved by the FDA for the treatment of COVID-19 in children, 28 days and older and weighing at least 3 kg, who are hospitalized or not hospitalized and have mild to moderate COVID-19 and are at high risk for disease progression.44 In a randomized, double-blind, placebo-controlled trial of non-hospitalized patients ≥12 years of age testing positive for SARS-CoV-2 and having at least one high-risk factor for COVID-19 disease progression, receipt of early remdesivir (given within 7 days of symptom onset) once daily for 3 days resulted in an 87% lower risk of hospitalization or death among 279 subjects receiving remdesivir than 283 subjects receiving placebo by day 28.43 A phase 2/3 single arm, open label study that included 53 children at least 28 days of age, weighing at least 3 kg, and receiving remdesivir for up to 10 days demonstrated that the safety and pharmacokinetics of remdesivir in young children were similar to adult data.45
    • Logistical considerations may limit the use of IV remdesivir in the outpatient setting.
    • Remdesivir IV for mild to moderate COVID-19 is approved for use in:
      • adults and children 28 days of age and weighing at least 3 kg, and
      • with laboratory-confirmed SARS-CoV-2, and
      • who are within 7 days of symptom onset, and
      • who are at high risk for progression to severe COVID-19, and
      • not hospitalized for COVID-19
    • The remdesivir IV dosage depends on age and weight as follows:
      • 3 kg to 40 kg: remdesivir 5 mg/kg on day 1 (loading dose), followed by 2.5 mg/kg once daily on day 2 and 3
      • ≥12 years and ≥40 kg: remdesivir 200 mg on day 1 (loading dose), followed by 100 mg IV daily on days 2 and 3
      • The dose is given once daily on 3 consecutive days; the intravenous infusion is administered over 30 to 120 minutes.
    • Adverse events were reported infrequently compared with placebo (0.7% vs 5.3%) and included nausea, headache, and cough. Allergic reactions and increased liver enzymes are also possible side effects. Patients should be monitored during and for at least 1 hour after the dose for possible infusion-related reactions.
    • Refer to the prescribing information for additional details.
  • Oral antivirals (Table 2): There are no available data regarding the safety, efficacy or pharmacokinetics of SARS-CoV-2 oral antivirals in children <12 years of age. Additional information will be added to this interim guidance as more pediatric data become available.
    • Paxlovid46
      • The FDA issued an EUA for the use of Paxlovid for the treatment of mild to moderate COVID-19 on the basis of results of a Phase 2/3 randomized, double-blind, placebo-controlled trial in high-risk individuals ≥18 years of age.47 Receipt of Paxlovid resulted in 88% relative risk reduction in COVID-19-related hospitalizations or death from any cause compared with individuals who received placebo through day 28; no children were included in this trial.48 Of note, 98% of SARS-CoV-2 variants in this trial were Delta; preliminary cell culture-based data suggest that nirmatrelvir retains antiviral activity against the SARS-CoV-2 Omicron variant.49-51 A phase 2 and 3 clinical trial assessing the safety and efficacy of paxlovid treatment in children 6-17 years of age with COVID-19 is underway.52
      • Paxlovid is copackaged as a combination of nirmatrelvir (a SARS-CoV-2 protease inhibitor, dispensed as two 150-mg tablets) and 100 mg of ritonavir (has no SARS-CoV-2 antiviral activity, but as a CYP3A inhibitor, increases nirmatrelvir blood concentrations). There are no PK/PD data in children; the authorized dose is expected to result in comparable serum drug concentrations in patients ≥12 years of age and weighing ≥40 kg.49
      • The EUA authorizes the use of Paxlovid in:
        • adults and children ≥12 years of age and weighing ≥40 kg, and
        • with laboratory-confirmed SARS-CoV-2, and
        • are within 5 days of symptom onset, and
        • who are at high risk for progression to severe COVID-19, and
        • not hospitalized for COVID-19
      • If providers consider the benefit of treatment outweighs the potential risk in an individual, eligible patient regardless of COVID-19 vaccination status, then Paxlovid should be initiated within 5 days of symptom onset; the 3 tablets should be taken together, preferably with a fatty meal, and swallowed whole, twice daily, for a maximum of 5 days. Patients who are prescribed Paxlovid as outpatients but worsen and require hospitalization for any reason (including worsening of COVID-19 symptoms) may complete the 5-day course under the EUA and per provider discretion.
      • The most frequent adverse events reported in clinical trials with Paxlovid include dysgeusia (metallic taste, 6% vs < 1%), diarrhea, hypertension and myalgias. Refer to the Fact Sheets for Healthcare Providers53 and for patients/caregivers54 for additional details. In addition, providers should be aware of the possibility of recurrence of milder symptoms and/or a new positive viral test (after having tested negative) that has been reported to occur 2 to 8 days after initial recovery and despite antiviral therapy, referred to as “COVID-19 rebound.”12
      • Paxlovid should not be used in individuals with severe hepatic (eg, Child-Pugh Class C) or renal impairment (creatinine clearance, CrCl <30 mL/min). Dosage adjustments are required for patients with moderate renal impairment (eg, CrCl 30-60 mL/min), with doses available in a different packaging configuration (Paxlovid 150 mg; 100 mg Dose Pack).55 In addition, clinicians should thoroughly review the medications the patient is taking; there is a potential for severe drug-drug interactions56 if given concurrently with other medications that rely on or induce CYP3A enzymes for metabolism and clearance.57 Ritonavir may reduce the efficacy of combined hormonal contraceptives; patients should be counseled on an effective alternative method of contraception.
    • Molnupiravir
      • The FDA issued an EUA for the use of molnupiravir for the treatment of mild to moderate COVID in high-risk, nonhospitalized adults for whom alternative COVID-19 treatment options are not clinically available or appropriate.58 This EUA was based on results of a Phase 3 randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of molnupiravir given within 5 days of symptom onset; molnupiravir led to a 30% reduction in the risk of all-cause hospitalization and death compared with placebo in nonhospitalized and unvaccinated, high-risk individuals ≥18 years of age through day 29.59 Children were not eligible to participate in the study because of concerns about effects on bone and cartilage growth.
      • Molnupiravir is the oral ribonucleoside prodrug, available in 200-mg capsules; dosage is 800 mg (4 capsules) twice a day for 5 days.
      • The EUA authorizes the use of molnupiravir in:
        • Individuals ≥18 years of age, and
        • with laboratory-confirmed SARS-CoV-2, and
        • are within 5 days of symptom onset, and
        • who are at high risk for progression to severe COVID-19, and
        • for whom other, FDA-authorized COVID-19 treatment options are not readily accessible, available, or clinically appropriate11,60
      • Molnupiravir has lower efficacy than the preferred treatment options in adults with COVID-19.12 If providers consider the benefit of treatment outweighs the potential risk in an individual, then molnupiravir should be initiated as soon as possible and within 5 days of symptom onset. Patients who are prescribed molnupiravir as outpatients but worsen and require hospitalization for any reason (including worsening of COVID-19 symptoms) may complete the 5-day course under the EUA and per provider discretion.
      • Adverse reactions reported to occur in ≥1% of clinical trial participants include diarrhea, nausea, and dizziness.59 No dosage adjustments are needed in patients with renal or hepatic impairment of any degree. Molnupiravir is not recommended for use in pregnancy given potential of fetal harm on the basis of animal data. Individuals of reproductive potential should be advised of the potential risk to the fetus and counseled regarding use of a reliable method of contraception during the treatment course and for 4 days after the last dose and be aware of the pregnancy surveillance program. Pregnant individuals should be encouraged to participate in the pregnancy surveillance program by calling 1-877-4231. In addition, molnupiravir should not be used if breastfeeding, including during the 5-day treatment and for 4 days following the last dose.
      • Current NIH guidelines recommend the use of molnupiravir in eligible patients only when appropriate mAb, Paxlovid, or remdesivir cannot be used.60 Refer to the Fact Sheets for health care providers and patients/caregivers61 and patients/families for additional details.61

Providers should review the antiviral fact sheets with eligible patients, provide patients an electronic or hard copy of the fact sheet, and document review, receipt, and counseling recommended within the fact sheets.54,61

The oral SARS-CoV-2 antivirals are not authorized to be initiated in children/adolescents who are hospitalized for COVID-19 or as pre- or postexposure prophylaxis. Providers should follow FDA EUA requirements and report side effects and adverse events related to antiviral therapies within 7 calendar days (1-800-FDA-1088).

The NIH Panel’s current outpatient treatment recommendations for mild to moderate COVID-19 in pediatric outpatients at high risk for disease progression or severity include Paxlovid and remdesivir.8

Lack of pediatric-specific data precludes the clear recommendation of one therapy over another. Providers will need to continue to evaluate multiple factors when selecting optimal treatment options for an individual patient, including age/weight, indication, SARS-CoV-2 subvariant circulation and local availability of therapies. Providers may refer to the risk assessment framework when considering COVID-19-directed therapies in children.8

What strategies may be considered in communities with resource constraints or limited access to SARS-CoV-2 therapies?

  • The COVID-19 pandemic has further highlighted ongoing health care disparities, including prescribing of SARS-CoV-2 mAb.62 The American Academy of Pediatrics (AAP) strongly supports the equitable distribution and availability of therapeutic medications and vaccinations to all eligible children and adolescents.
  • Given limited supply chains and logistical constraints, there will be varying access to SARS-CoV-2 mAb and antivirals geographically, requiring additional triage for patients at highest risk for COVID-19.11 State and local health departments will allocate therapies to health care facilities. Considerations when assessing COVID-19 risk and prioritizing SARS-CoV-2 therapies for an individual patient should take into account host, situational, and ethical63 factors, including:
    • Prioritizing the treatment of SARS-CoV-2 infection in patients at highest risk for COVID-19 complications and hospitalizations.11
    • Prioritizing preexposure prophylaxis to patients identified to be at highest risk of COVID-19 complications. When outpatient therapies are extremely limited, prioritizing among the most severely immunocompromised individuals may be prudent for both treatment and preexposure prophylaxis, followed by severely immunocompromised with additional COVID-19 risk factors.
    • COVID-19 vaccination status: Individuals who are unvaccinated or incompletely vaccinated against COVID-19 or fully vaccinated individuals ≥2 weeks after completing their COVID-19 mRNA primary vaccine series but not expected to mount an adequate vaccine immune response are at higher risk for hospitalization than fully vaccinated, nonimmunocompromised individuals.65-67

What medications should NOT be used to treat or prevent the progression of COVID-19 in children and adolescents?

  • There is NO conclusive evidence to support the efficacy and safety of the following medications for routine use in the treatment or prevention of COVID-19 in children and adolescents. It is strongly recommended that these unproven interventions not be prescribed, and parents be counseled against their use. In addition to showing no efficacy against COVID-19, inappropriate use of these antimicrobials cause significant harm.68,69 The following are NOT recommended to be prescribed for COVID-19:
    • Azithromycin: Results of randomized trials in ambulatory subjects conclude that azithromycin did not result in more or faster COVID-19 symptom improvement compared with placebo and had no meaningful benefit in preventing COVID-19 hospitalizations.70,71
    • Ivermectin72: Inappropriate use of this antiparasitic in patients with COVID-19 has led to increased reports to poison control centers of severe illness and has prompted a CDC Health Advisory.73
    • Hydroxychloroquine/chloroquine: Moderate-quality evidence suggests that these agents lack efficacy in reducing short-term mortality or need for hospitalization in patients with COVID-1974; in addition, serious cardiac events, including QTc prolongation, have been reported.75
    • Systemic corticosteroids are NOT recommended for treating patients with mild to moderate COVID-19 who do not require supplemental oxygen for their SARS-CoV-2 infection, given lack of proven benefit and possible harm.76 Recent updates to the COVID-19 treatment guidelines recommend against the use of dexamethasone or other systemic glucocorticosteroids for this indication, in this population.60

Additional Information

There is much misinformation on the internet/social media. Pediatricians, pediatric medical subspecialists and pediatric surgical specialists are encouraged to refer patients and families to reputable, up-to-date COVID-19 resources:

aRegarding assessment of immunosuppression: Moderate to severe immunocompromise by host factors as described above. Receipt of immunosuppressive therapies leading to severe immunocompromise includes receipt of: T lymphocyte-depleting (eg, leading to CD4+ T-lymphocyte count <100-300 cells/mm3 or CD4+ T-lymphocyte percentage <15% for children) or B lymphocyte-depleting (eg, rituximab) agents; daily systemic corticosteroids with a prednisone dose equivalent of ≥20 mg/day (or ≥2 mg/kg/day in children who weigh <10 kg) for ≥2 weeks; alkylating agents, antimetabolites, transplant-related immunosuppressive medications, cancer chemotherapeutic agents classified as severely immunosuppressive, and other biologic agents that are considered immunosuppressive or immunomodulatory, particularly when used in combination.

 

Table 1. Summary of SARS-CoV-2 Monoclonal Antibodies Currently Authorized for Use in Eligible Children and Adolescents

Table 1 - Summary 10-31-22.jpg

View full table

ASAP indicates as soon as possible; EUA, Emergency Use Authorization; IV, intravenous; IM, intramuscular; PrEP, preexposure prophylaxis

Table 2. Summary of SARS-CoV-2 Oral Antivirals Currently Authorized for Use in Mild to Moderate COVID-19

Table 2 - Summary 10-31-22.jpg

View full table

Table 3. Summary of Potential SARS-CoV-2 Therapies in the Context of SARS-CoV-2 Omicron Circulation and Based on Indication and EUA Age/Weight Inclusion Criteria in Children and Adolescents at High Risk for Progressing to Severe COVID-19

Table 3 - Summary 10-31-22.jpg

IM, intramuscular; IV, intravenous; PO, per os; n/a not applicable.
Additional key information for outpatient therapies currently authorized in the United States is available here: https://www.phe.gov/emergency/events/COVID19/therapeutics/Pages/Side-by-Side-Overview-of-mAbs-Treatment.aspxx1

Table 4. Intramuscular (IM) Dosing and Administration of Tixagevimab Copackaged with Cilgavimab (Evusheld)39

Table 4 Summary 10-31-22.jpg


Interim Guidance Disclaimer:
The COVID-19 clinical interim guidance provided here has been updated based on current evidence and information available at the time of publishing. Guidance will be regularly reviewed with regards to the evolving nature of the pandemic and emerging evidence. All interim guidance will be presumed to expire on June 30, 2023 unless otherwise specified.

Last Updated

10/31/2022

Source

American Academy of Pediatrics