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I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at pdnews@mdedge.com.
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at pdnews@mdedge.com.
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at pdnews@mdedge.com.
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.