Emergency management and asthma risk in young Medicaid-enrolled children with recurrent wheeze.

OBJECTIVES: To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. METHODS: Retrospective cohort study of Medicaid-enrolled children 0-3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. RESULTS: During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. CONCLUSIONS: Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies.

Impact of a discharge prescription for dexamethasone on outcomes of children treated in the emergency department for acute asthma exacerbations.

OBJECTIVE: To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED). STUDY DESIGN: Prospective study of children 2-18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7-10 days after discharge. RESULTS: 564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes. CONCLUSIONS: Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia.

OBJECTIVE: To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED). METHODS: Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit. Outcomes were QoL measures and unplanned visits. Multivariable regression was used to evaluate the association between corticosteroid therapy and outcomes. RESULTS: Of 898 children, 162 (18%) received corticosteroids. Children who received corticosteroids were more frequently boys (62%), Black (45%), had history of asthma (58%), previous pneumonia (16%), presence of wheeze (74%), and more severe illness at presentation (6%). Ninety-six percent were treated for asthma as defined by report of asthma or receipt of ß-agonist in the ED. Receipt of corticosteroids was not associated with QoL measures: days of activity missed (adjusted incident rate ratio [aIRR], 0.84; 95% confidence interval [CI], 0.63-1.11) and days of work missed (aIRR, 0.88; 95% CI, 0.60-1.27). There was a statistically significant interaction between age (>2 years) and corticosteroids receipt; the patients had fewer days of activity missed (aIRR, 0.62; 95% CI, 0.46-0.83), with no effect on children 2 years or younger (aIRR, 0.83; 95% CI, 0.54-1.27). Corticosteroid treatment was not associated with unplanned visit (odds ratio, 1.37; 95% CI, 0.69-2.75). CONCLUSIONS: In this cohort of children with suspected CAP, receipt of corticosteroids was associated with asthma history and was not associated with missed days of activity or work, except in a subset of children aged older than 2 years.

Viral Detection Is Associated With Severe Disease in Children With Suspected Community-Acquired Pneumonia.

OBJECTIVE: To evaluate the role of virus detection on disease severity among children presenting to the emergency department (ED) with suspected community-acquired pneumonia (CAP). METHODS: We performed a single-center prospective study of children presenting to a pediatric ED with signs and symptoms of a lower respiratory tract infection and who had a chest radiograph performed for suspected CAP. We included patients who had virus testing, with results classified as negative for virus, human rhinovirus, respiratory syncytial virus (RSV), influenza, and other viruses. We evaluated the association between virus detection and disease severity using a 4-tiered measure of disease severity based on clinical outcomes, ranging from mild ( discharged from the ED) to severe (receipt of positive-pressure ventilation, vasopressors, thoracostomy tube placement, or extracorporeal membrane oxygenation, intensive care unit admission, diagnosis of severe sepsis or septic shock, or death) in models adjusted for age, procalcitonin, C-reactive protein, radiologist interpretation of the chest radiograph, presence of wheeze, fever, and provision of antibiotics. RESULTS: Five hundred seventy-three patients were enrolled in the parent study, of whom viruses were detected in 344 (60%), including 159 (28%) human rhinovirus, 114 (20%) RSV, and 34 (6%) with influenza. In multivariable models, viral infections were associated with increasing disease severity, with the greatest effect noted with RSV (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.30-4.81) followed by rhinovirus (aOR, 2.18; 95% CI, 1.27-3.76). Viral detection was not associated with increased severity among patients with radiographic pneumonia (n = 223; OR, 1.82; 95% CI, 0.87-3.87) but was associated with severity among patients without radiographic pneumonia (n = 141; OR, 2.51; 95% CI, 1.40-4.59). CONCLUSIONS: The detection of a virus in the nasopharynx was associated with more severe disease compared with no virus; this finding persisted after adjustment for age, biomarkers, and radiographic findings. Viral testing may assist with risk stratification of patients with lower respiratory tract infections.

Method/ology of Phases of Biomarker Discovery.

Biomarkers are commonly used in pediatric medicine to identify disease and guide clinical management for children. Biomarkers can be used to predict risk of disease, provide diagnostic clarification, and offer prognostic expectations. Specimens for biomarker testing might require noninvasive collection (eg, urine, exhaled breath) or invasive procedures (eg, blood, bronchoalveolar lavage) and testing might use various methodologies (eg, genomics, transcriptomics, proteomics, metabolomics). Specimen type and testing methodology depends on the disease of interest, ability to obtain sample, and availability of biomarker testing. To develop a new biomarker, researchers must first identify and validate the target, and then determine the test characteristics of the biomarker. Once it has undergone initial development and testing, a new biomarker is then tested in the clinical setting before being implemented into practice. An ideal biomarker is one that is feasible to obtain, readily quantifiable, and offers meaningful information that impacts care. Learning how to reliably interpret the performance and clinical application of a new biomarker is an important skillset for all pediatricians in the hospital setting. Here we provide a high-level overview of the process from biomarker discovery to application. In addition, we provide an example for the real-world application of biomarkers as an opportunity for clinicians to build on their ability to critically evaluate, interpret, and implement biomarkers in clinical practice.

Defining Treatment Response for Clinical Trials of Pediatric Acute Asthma.

BACKGROUND: An agreed-upon definition of treatment response for clinical trials of pediatric acute asthma does not exist, limiting meaningful comparisons among therapeutic interventions and advances in asthma management. OBJECTIVE: To develop a consensus definition of treatment response for clinical trials of pediatric acute asthma. METHODS: A multidisciplinary panel of 22 experts participated in a Web-based modified Delphi process to achieve consensus on a definition of treatment response. Round 1 consisted of closed- and open-ended questions in which panelists ranked measures of treatment response developed by literature review, suggested additional measures, and explained their responses. In rounds 2 and 3, panelists reviewed summary statistics of the panel's rating from prior rounds and reconsidered their rankings. In round 3, pairwise ranking was performed to determine the ranked importance of components. Consensus was defined as 70% or greater agreement among panelists choosing Likert-scale values of 1 to 6 (extremely unimportant to extremely important) and an interquartile range less than 2. RESULTS: Drawing on results from the expert panel, we developed a definition of treatment response that includes Clinical Severity Score, need for additional therapies, and hospitalization. Clinical Severity Score encompassed most ranked criteria (eg, respiratory distress, wheeze) for a treatment response definition. Panelists recommended that a valid and pragmatic severity score be used consistently across institutions. Panelists also achieved consensus on the top 10 criteria that appropriately classify need for hospitalization. CONCLUSIONS: This consensus definition of treatment response can be used in clinical trials of children with acute asthma to standardize outcome measurement and report meaningful outcomes.

Factors Associated With Clinician Self-Reported Resource Use in Acute Care and Ambulatory Pediatrics.

The objective of this study is to determine predictors of resource use among pediatric providers for common respiratory illnesses. We surveyed pediatric primary care, emergency department (ED)/urgent care (UC), and hospital medicine providers at a free-standing children's hospital system. Five clinical vignettes assessed factors affecting resource use for upper respiratory infections, bronchiolitis, and pneumonia, including provider-type, practice location, tolerance to uncertainty, and medical decision-making behaviors. The response rate was 75.3% (168/223). The ED/UC and primary care providers had higher vignette scores, indicating higher resource use, compared with inpatient providers; advanced practice providers (APPs) had higher vignette scores compared with physicians. In multivariate analysis, being an ED/UC provider, an APP, and greater concern for bad outcomes were associated with higher vignette scores. Overall, provider type and location of practice may predict resource use for children with respiratory illnesses. Interventions targeted at test-maximizing providers may improve quality of care and reduce resource burden.

Antibiotic use and outcomes among children hospitalized with suspected pneumonia.

BACKGROUND: Although viral etiologies predominate, antibiotics are frequently prescribed for community-acquired pneumonia (CAP). OBJECTIVE: We evaluated the association between antibiotic use and outcomes among children hospitalized with suspected CAP. DESIGNS, SETTINGS AND PARTICIPANTS: We performed a secondary analysis of a prospective cohort of children hospitalized with suspected CAP. INTERVENTION: The exposure was the receipt of antibiotics in the emergency department (ED). MAIN OUTCOME AND MEASURES: Clinical outcomes included length of stay (LOS), care escalation, postdischarge treatment failure, 30-day ED revisit, and quality-of-life (QoL) measures from a follow-up survey 7-15 days post discharge. To minimize confounding by indication (e.g., radiographic CAP), we performed inverse probability treatment weighting with propensity analyses. RESULTS: Among 523 children, 66% were <5 years, 88% were febrile, 55% had radiographic CAP, and 55% received ED antibiotics. The median LOS was 41 h (IQR: 25, 54). After propensity analyses, there were no differences in LOS, escalated care, treatment failure, or revisits between children who received antibiotics and those who did not. Seventy-one percent of patients completed follow-up surveys after discharge. Among 16% of patients with fevers after discharge, the median fever duration was 2 days, and those who received antibiotics had a 37% decrease in the mean number of days with fever (95% confidence interval: 20% and 51%). We found no statistical differences in other QoL measures.

Identifying Potentially Unnecessary Hospitalizations in Children With Pneumonia.

OBJECTIVE: To characterize the outcomes of children with community acquired pneumonia (CAP) across 41 United States hospitals and evaluate factors associated with potentially unnecessary admissions. METHODS: We performed a cross-sectional study of patients with CAP from 41 United States pediatric hospitals and evaluated clinical outcomes using a composite ordinal severity outcome: mild-discharged (discharged from the emergency department), mild-admitted (hospitalized without other interventions), moderate (provision of intravenous fluids, supplemental oxygen, broadening of antibiotics, complicated pneumonia, and presumed sepsis) or severe (ICU, positive-pressure ventilation, vasoactive infusion, chest drainage, extracorporeal membrane oxygenation, severe sepsis, or death). Our primary outcome was potentially unnecessary admissions (ie, mild-admitted). Among mild-discharged and mild-admitted patients, we constructed a generalized linear mixed model for mild-admitted severity and assessed the role of fixed (demographics and clinical testing) and random effects (institution) on this outcome. RESULTS: Of 125 180 children, 68.3% were classified as mild-discharged, 6.6% as mild-admitted, 20.6% as moderate and 4.5% as severe. Among admitted patients (n = 39 692), 8321 (21%) were in the mild-admitted group, with substantial variability in this group across hospitals (median 19.1%, interquartile range 12.8%-28.4%). In generalized linear mixed models comparing mild-admitted and mild-discharge severity groups, hospital had the greatest contribution to model variability compared to all other variables. CONCLUSIONS: One in 5 hospitalized children with CAP do not receive significant interventions. Among patients with mild disease, institutional variation is the most important contributor to predict potentially unnecessary admissions. Improved prognostic tools are needed to reduce potentially unnecessary hospitalization of children with CAP.

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. Exposure: SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Factors Associated With Antibiotic Use for Children Hospitalized With Pneumonia.

BACKGROUND: Antibiotics are frequently used for community-acquired pneumonia (CAP), although viral etiologies predominate. We sought to determine factors associated with antibiotic use among children hospitalized with suspected CAP. METHODS: We conducted a prospective cohort study of children who presented to the emergency department (ED) and were hospitalized for suspected CAP. We estimated risk factors associated with receipt of ≥1 dose of inpatient antibiotics and a full treatment course using multivariable Poisson regression with an interaction term between chest radiograph (CXR) findings and ED antibiotic use. We performed a subgroup analysis of children with nonradiographic CAP. RESULTS: Among 477 children, 60% received inpatient antibiotics and 53% received a full course. Factors associated with inpatient antibiotics included antibiotic receipt in the ED (relative risk 4.33 [95% confidence interval, 2.63-7.13]), fever (1.66 [1.22-2.27]), and use of supplemental oxygen (1.29 [1.11-1.50]). Children with radiographic CAP and equivocal CXRs had an increased risk of inpatient antibiotics compared with those with normal CXRs, but the increased risk was modest when antibiotics were given in the ED. Factors associated with a full course were similar. Among patients with nonradiographic CAP, 29% received inpatient antibiotics, 21% received a full course, and ED antibiotics increased the risk of inpatient antibiotics. CONCLUSIONS: Inpatient antibiotic utilization was associated with ED antibiotic decisions, CXR findings, and clinical factors. Nearly one-third of children with nonradiographic CAP received antibiotics, highlighting the need to reduce likely overuse. Antibiotic decisions in the ED were strongly associated with decisions in the inpatient setting, representing a modifiable target for future interventions.

Validation of Prediction Models for Pneumonia Among Children in the Emergency Department.

BACKGROUND: Several prediction models have been reported to identify patients with radiographic pneumonia, but none have been validated or broadly implemented into practice. We evaluated 5 prediction models for radiographic pneumonia in children. METHODS: We evaluated 5 previously published prediction models for radiographic pneumonia (Neuman, Oostenbrink, Lynch, Mahabee-Gittens, and Lipsett) using data from a single-center prospective study of patients 3 months to 18 years with signs of lower respiratory tract infection. Our outcome was radiographic pneumonia. We compared each model's area under the receiver operating characteristic curve (AUROC) and evaluated their diagnostic accuracy at statistically-derived cutpoints. RESULTS: Radiographic pneumonia was identified in 253 (22.2%) of 1142 patients. When using model coefficients derived from the study dataset, AUROC ranged from 0.58 (95% confidence interval, 0.52-0.64) to 0.79 (95% confidence interval, 0.75-0.82). When using coefficients derived from original study models, 2 studies demonstrated an AUROC >0.70 (Neuman and Lipsett); this increased to 3 after deriving regression coefficients from the study cohort (Neuman, Lipsett, and Oostenbrink). Two models required historical and clinical data (Neuman and Lipsett), and the third additionally required C-reactive protein (Oostenbrink). At a statistically derived cutpoint of predicted risk from each model, sensitivity ranged from 51.2% to 70.4%, specificity 49.9% to 87.5%, positive predictive value 16.1% to 54.4%, and negative predictive value 83.9% to 90.7%. CONCLUSIONS: Prediction models for radiographic pneumonia had varying performance. The 3 models with higher performance may facilitate clinical management by predicting the risk of radiographic pneumonia among children with lower respiratory tract infection.

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.