Chiotos, Kathleen

Abstract 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.

OBJECTIVE To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8–5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1–1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38). CONCLUSION In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. Design: Retrospective study. Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. Interventions: None. Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Purpose of review Over the course of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that the clinical features, epidemiology, and outcomes of COVID-19 are distinct in children relative to adults. In this review, we will present recent pediatric studies informing our current understanding of COVID-19 in children, and review pediatric considerations surrounding disease transmission, currently available therapies, and vaccination. Recent findings Recent studies have shed light on the clinical epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, identifying a high prevalence of asymptomatic and mild infections, with severe COVID-19 infrequently reported. Several adult clinical trials have informed the use of remdesivir, anti-SARS-CoV-2 monoclonal antibodies, dexamethasone, and tocilizumab in the management of COVID-19. Associations between underlying comorbid medical conditions and severe outcomes, as well as transmission dynamics of SARS-CoV-2 in children, are complex and warrant further study. Finally, highly efficacious vaccines are available for adults and adolescents, with pediatric trials ongoing. Summary Children generally fare well with acute COVID-19 infection, though critical illness is possible. Future research should focus on clarifying the role of children in SARS-CoV-2 transmission and optimal prevention strategies, particularly in the school setting, as well as evaluating pediatric vaccine candidates.

OBJECTIVES: To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN: Retrospective cohort study. SETTING: Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS: Children less than 18 years with severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS: Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2–12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5–11] vs 5.3 d [interquartile range, 3–11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61–5.40]; p < 0.01). CONCLUSIONS: This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2–related illness stratified by multisystem inflammatory syndrome in children.

Abstract 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.