Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.

Race, Ethnicity, and Health Disparities in US Children With COVID-19: A Review of the Evidence and Recommendations for the Future.

Coronavirus disease 2019 (COVID-19) is an important cause of morbidity in children in the United States (U.S.). Moreover, the U.S. has witnessed significant disparities affecting American Indian/Alaska Native, Black, and Hispanic/Latino children, stemming from systemic racism and social-structural inequalities and not differences in innate biological susceptibility. We review what is known on COVID-19 and health disparities in disease burden, access to care, pharmaceutical interventions, and clinical research in children, with a focus on the U.S. context. In addition, we propose strategies to communicate scientific data in ways that do not promote racism and biological susceptibility themes, and to address pediatric disparities in clinical infectious diseases research.

Comorbidities Associated with Hospitalization and Progression Among Adolescents with Symptomatic Coronavirus Disease 2019.

OBJECTIVE: To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19). STUDY DESIGN: We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. RESULTS: A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization. CONCLUSIONS: SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

Comorbidities associated with hospitalization and progression among adolescents with symptomatic COVID-19

Objectives To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy, we evaluated the relationship between comorbidities and hospitalization among US adolescents with symptomatic COVID-19. Study design We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents 12-17 years old in the Pediatric COVID-19 U.S. registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. Results 1877 patients met inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR 6.9 [3.0-15.9]), immunocompromising condition (aOR 6.4 [3.8-10.8]), obesity (aOR 3.2 [2.1-4.9]), diabetes (aOR 3.0 [1.4-6.2]), neurologic disease (aOR 2.8 [1.8-4.3]), and pulmonary disease (excluding mild asthma) (aOR 1.9 [1.2-3.1]). Heart disease and chronic kidney disease were not independently associated with hospitalization. Conclusions SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Differentiating multisystem inflammatory syndrome in children: a single-centre retrospective cohort study.

OBJECTIVE: Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre. STUDY DESIGN: We identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C. RESULTS: We identified 50 confirmed MIS-C cases (MIS-C+) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C-). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C+ patients. MIS-C+ and MIS-C- patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension. CONCLUSIONS: Among hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Non-SARS-CoV-2 Infections Among Patients Evaluated for MIS-C Associated With COVID-19.

Clinical features of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 are nonspecific. In this retrospective cohort study of 39 patients evaluated for MIS-C, 11 had non-SARS-CoV-2 infections, 3 of whom were also diagnosed with MIS-C. Clinical features were similar in patients with MIS-C and patients with non-SARS-CoV-2 infections. Clinicians should consider non-SARS-CoV-2 infections in patients undergoing MIS-C evaluation.