Predictors of Invasive Bacterial Infection in Febrile Infants Aged 2 to 6 Months in the Emergency Department.

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2-6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing.

Contaminant Organism Growth in Febrile Infants at Low Risk for Invasive Bacterial Infection.

In this multicenter, cross-sectional, secondary analysis of 4042 low-risk febrile infants, nearly 10% had a contaminated culture obtained during their evaluation (4.9% of blood cultures, 5.0% of urine cultures, and 1.8% of cerebrospinal fluid cultures). Our findings have important implications for improving sterile technique and reducing unnecessary cultures.

Prevalence and Management of Invasive Bacterial Infections in Febrile Infants Ages 2 to 6 Months.

STUDY OBJECTIVE: Validated prediction rules identify febrile neonates at low risk for invasive bacterial infection. The optimal approach for older febrile infants, however, remains uncertain. METHODS: We performed a retrospective cohort and nested case-control study of infants 2 to 6 months of age presenting with fever (≥38.0 °C) to 1 of 5 emergency departments. The study period was from 2011 to 2019. The primary outcome was invasive bacterial infection, defined by the growth of pathogenic bacteria from either blood or cerebrospinal fluid culture. Secondary outcomes included obtaining bacterial cultures (blood, cerebrospinal fluid, or urine), administering antibiotics, and hospitalization. For the nested case-control study, we age-matched infants with invasive bacterial infection to 3 infants without invasive bacterial infection, sampled from the overall cohort. RESULTS: There were 21,150 eligible patient encounters over 9-years, and 101 infants had a documented invasive bacterial infection (0.48%; 95% confidence interval [CI], 0.39% to 0.58%). Invasive bacterial infection prevalence ranged from 0.2% to 0.6% among the 5 sites. The frequency of bacterial cultures ranged from 14.5% to 53.5% for blood, 1.6% to 12.9% for cerebrospinal fluid, and 31.8% to 63.2% for urine. Antibiotic administration varied from 19.2% to 46.7% and hospitalization from 16.6% to 28.3%. From the case-control study, the estimated invasive bacterial infection prevalence for previously healthy, not pretreated, and well-appearing febrile infants was 0.32% (95% CI, 0.24% to 0.41%). CONCLUSION: Although invasive bacterial infections were uncommon among febrile infants 2 to 6 months in the emergency department, the approach to diagnosis and management varied widely between sites. Therefore, evidence-based guidelines are needed to reduce low-value testing and treatment while avoiding missing infants with invasive bacterial infections.

Multisystem Inflammatory Syndrome in Children: Examining Emerging Data and Identifying Key Knowledge Gaps.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a syndrome of abnormal immune response after severe acute respiratory syndrome coronavirus 2 infection that can result in organ dysfunction including severe cardiovascular compromise in children. Increased evidence supports a clinical and laboratory profile in MIS-C distinct from Kawasaki disease, with MIS-C typically occurring in older children and with more prominent gastrointestinal and neurologic symptoms, as well as increased inflammation, lymphopenia, and cardiac injury on laboratory testing. However, high-level evidence regarding best practices for treatment and long-term outcomes in MIS-C is limited.

Distinguishing Multisystem Inflammatory Syndrome in Children From Kawasaki Disease and Benign Inflammatory Illnesses in the SARS-CoV-2 Pandemic.

OBJECTIVE: The aim of the study was to compare presenting clinical and laboratory features among children meeting the surveillance definition for multisystem inflammatory syndrome in children (MIS-C) across a range of illness severities. METHODS: This is a retrospective single-center study of patients younger than 21 years presenting between March 1 and May 15, 2020. Included patients met the Centers for Disease Control and Prevention criteria for MIS-C (inflammation, fever, involvement of 2 organ systems, lack of alternative diagnoses). We defined 3 subgroups by clinical outcomes: (1) critical illness requiring intensive care interventions; (2) patients meeting Kawasaki disease (KD) criteria but not requiring critical care; and (3) mild illness not meeting either criteria. A comparator cohort included patients with KD at our institution during the same time frame in 2019. RESULTS: Thirty-three patients were included (5, critical; 8, 2020 KD; 20, mild). The median age for the critical group was 10.9 years (2.7 for 2020 KD; 6.0 for mild, P = 0.033). The critical group had lower median absolute lymphocyte count (850 vs 3005 vs 2940/uL, P = 0.005), platelets (150 vs 361 vs 252 k/uL, P = 0.005), and sodium (129 vs 136 vs 136 mmol/L, P = 0.002), and higher creatinine (0.7 vs 0.2 vs 0.3 mg/dL, P = 0.002). In the critical group, 60% required vasoactive medications, and 40% required mechanical ventilation. Clinical and laboratories features were similar between the 2020 and 2019 KD groups. CONCLUSIONS: We describe 3 groups with inflammatory syndromes during the SARS-CoV-2 pandemic. The initial profile of lymphopenia, thrombocytopenia, hyponatremia, and abnormal creatinine may help distinguish critically ill MIS-C patients from classic/atypical KD or more benign acute inflammation.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections.

OBJECTIVE: To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis). STUDY DESIGN: Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt. RESULTS: Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths. CONCLUSIONS: Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI.

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone. CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

COD, nutrient removal and disinfection efficiency of a combined subsurface and surface flow constructed wetland: A case study.

A constructed wetland system composed of a subsurface flow wetland, a surface flow wetland and a facultative pond was studied from July 2008 until May 2012. It was created to treat the domestic sewage produced by a hamlet of 150 inhabitants. Monthly physicochemical and microbiological analyses were carried out in order to evaluate the removal efficiency of each stage of the process and of the total treatment system. Pair-wise Student's t-tests showed that the mean removal of each considered parameter was significantly different (α = 0.05) between the various treatment phases. Two-way ANOVA and Tukey's HSD tests were used to find significant differences between wetland types and seasons in the removal efficiency of the considered water quality parameters. Significant differences in percent removal efficiency between the treatment phases were observed for total phosphorus, total nitrogen, ammonia nitrogen and organic load (expressed as Chemical Oxygen Demand). In general, the wastewater treatment was carried by the sub-superficial flow phase mainly, both in growing season and in quiescence season. Escherichia coli removal ranged from 98% in quiescence season to >99% in growing season (approximately 2-3 orders of magnitude). The inactivation of fecal bacteria was not influenced by the season, but only by the treatment phase.

Prognostic clinical decision support for pneumonia in the emergency department: A randomized trial.

BACKGROUND: Hospitalization rates for childhood pneumonia vary widely. Risk-based clinical decision support (CDS) interventions may reduce unwarranted variation. METHODS: We conducted a pragmatic randomized trial in two US pediatric emergency departments (EDs) comparing electronic health record (EHR)-integrated prognostic CDS versus usual care for promoting appropriate ED disposition in children (<18 years) with pneumonia. Encounters were randomized 1:1 to usual care versus custom CDS featuring a validated pneumonia severity score predicting risk for severe in-hospital outcomes. Clinicians retained full decision-making authority. The primary outcome was inappropriate ED disposition, defined as early transition to lower- or higher-level care. Safety and implementation outcomes were also evaluated. RESULTS: The study enrolled 536 encounters (269 usual care and 267 CDS). Baseline characteristics were similar across arms. Inappropriate disposition occurred in 3% of usual care encounters and 2% of CDS encounters (adjusted odds ratio: 0.99, 95% confidence interval: [0.32, 2.95]) Length of stay was also similar and adverse safety outcomes were uncommon in both arms. The tool's custom user interface and content were viewed as strengths by surveyed clinicians (>70% satisfied). Implementation barriers include intrinsic (e.g., reaching the right person at the right time) and extrinsic factors (i.e., global pandemic). CONCLUSIONS: EHR-based prognostic CDS did not improve ED disposition decisions for children with pneumonia. Although the intervention's content was favorably received, low subject accrual and workflow integration problems likely limited effectiveness. Clinical Trials Registration: NCT06033079.

Race, Ethnicity, Language, and the Treatment of Low-Risk Febrile Infants.

Importance: Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language. Objective: To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection. Design, Setting, and Participants: This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 to July 2023. Pediatric emergency departments were determined through the Pediatric Emergency Medicine Collaborative Research Committee. Well-appearing febrile infants aged 29 to 60 days at low risk of invasive bacterial infection based on blood and urine testing were included. Data were available for 9847 infants, and 4042 were included following exclusions for ill appearance, medical history, and diagnosis of a focal infectious source. Exposures: Infant race and ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White, and other race or ethnicity) and language used for medical care (English and language other than English). Main Outcomes and Measures: The primary outcome was receipt of at least 1 of lumbar puncture, empirical antibiotics, or hospitalization. We performed bivariate and multivariable logistic regression with sum contrasts for comparisons. Individual components were assessed as secondary outcomes. Results: Across 34 sites, 4042 infants (median [IQR] age, 45 [38-53] days; 1561 [44.4% of the 3516 without missing sex] female; 612 [15.1%] non-Hispanic Black, 1054 [26.1%] Hispanic, 1741 [43.1%] non-Hispanic White, and 352 [9.1%] other race or ethnicity; 3555 [88.0%] English and 463 [12.0%] language other than English) met inclusion criteria. The primary outcome occurred in 969 infants (24%). Race and ethnicity were not associated with the primary composite outcome. Compared to the grand mean, infants of families that use a language other than English had higher odds of the primary outcome (adjusted odds ratio [aOR]; 1.16; 95% CI, 1.01-1.33). In secondary analyses, Hispanic infants, compared to the grand mean, had lower odds of hospital admission (aOR, 0.76; 95% CI, 0.63-0.93). Compared to the grand mean, infants of families that use a language other than English had higher odds of hospital admission (aOR, 1.08; 95% CI, 1.08-1.46). Conclusions and Relevance: Among low-risk febrile infants, language used for medical care was associated with the use of at least 1 nonindicated intervention, but race and ethnicity were not. Secondary analyses highlight the complex intersectionality of race, ethnicity, language, and health inequity. As inequitable care may be influenced by communication barriers, new guidelines that emphasize patient-centered communication may create disparities if not implemented with specific attention to equity.

Validation of Childhood Pneumonia Prognostic Models for Use in Emergency Care Settings.

BACKGROUND: Unwarranted variation in disposition decisions exist among children with pneumonia. We validated three prognostic models for predicting pneumonia severity among children in the emergency department (ED) and hospital. METHODS: We performed a two-center, prospective study of children 6 months to <18 years presenting to the ED with pneumonia from January 2014 to May 2019. We evaluated three previously developed disease-specific prognostic models which use demographic, clinical, and diagnostic predictor variables, with each model estimating risk for Very Severe (mechanical ventilation or shock), Severe (ICU without very severe features), and Moderate/Mild (Hospitalization without severe features or ED discharge) pneumonia. Predictive accuracy was measured using discrimination (concordance or c-statistic) and re-calibration. RESULTS: There were 1088 children included in one or more of the three models. Median age was 3.6 years and the majority of children were male (53.7%) and identified as non-Hispanic White (63.7%). The distribution for the ordinal severity outcome was mild or moderate (79.1%), severe (15.9%), and very severe (4.9%). The three models each demonstrated excellent discrimination (C-statistic range across models [0.786-0.803]) with no appreciable degradation in predictive accuracy from the derivation cohort. CONCLUSIONS: All three prognostic models accurately identified risk for three clinically meaningful levels of pneumonia severity and demonstrated very good predictive performance. Physiologic variables contributed the most to model prediction. Application of these objective tools may help standardize and improve disposition and other management decisions for children with pneumonia.

Antibiotic clinical decision support for pneumonia in the ED: A randomized trial.

BACKGROUND: Electronic health record-based clinical decision support (CDS) is a promising antibiotic stewardship strategy. Few studies have evaluated the effectiveness of antibiotic CDS in the pediatric emergency department (ED). OBJECTIVE: To compare the effectiveness of antibiotic CDS vs. usual care for promoting guideline-concordant antibiotic prescribing for pneumonia in the pediatric ED. DESIGN: Pragmatic randomized clinical trial. SETTING AND PARTICIPANTS: Encounters for children (6 months-18 years) with pneumonia presenting to two tertiary care children s hospital EDs in the United States. INTERVENTION: CDS or usual care was randomly assigned during 4-week periods within each site. The CDS intervention provided antibiotic recommendations tailored to each encounter and in accordance with national guidelines. MAIN OUTCOME AND MEASURES: The primary outcome was exclusive guideline-concordant antibiotic prescribing within the first 24 h of care. Safety outcomes included time to first antibiotic order, encounter length of stay, delayed intensive care, and 3- and 7-day revisits. RESULTS: 1027 encounters were included, encompassing 478 randomized to usual care and 549 to CDS. Exclusive guideline-concordant prescribing did not differ at 24 h (CDS, 51.7% vs. usual care, 53.3%; odds ratio [OR] 0.94 [95% confidence interval [CI]: 0.73, 1.20]). In pre-specified stratified analyses, CDS was associated with guideline-concordant prescribing among encounters discharged from the ED (74.9% vs. 66.0%; OR 1.53 [95% CI: 1.01, 2.33]), but not among hospitalized encounters. Mean time to first antibiotic was shorter in the CDS group (3.0 vs 3.4 h; p = .024). There were no differences in safety outcomes. CONCLUSIONS: Effectiveness of ED-based antibiotic CDS was greatest among those discharged from the ED. Longitudinal interventions designed to target both ED and inpatient clinicians and to address common implementation challenges may enhance the effectiveness of CDS as a stewardship tool.

Improving the Quality of Written Discharge Instructions: A Multisite Collaborative Project.

BACKGROUND AND OBJECTIVES: Written discharge instructions help to bridge hospital-to-home transitions for patients and families, though substantial variation in discharge instruction quality exists. We aimed to assess the association between participation in an Institute for Healthcare Improvement Virtual Breakthrough Series collaborative and the quality of pediatric written discharge instructions across 8 US hospitals. METHODS: We conducted a multicenter, interrupted time-series analysis of a medical records-based quality measure focused on written discharge instruction content (0-100 scale, higher scores reflect better quality). Data were from random samples of pediatric patients (N = 5739) discharged from participating hospitals between September 2015 and August 2016, and between December 2017 and January 2020. These periods consisted of 3 phases: 1. a 14-month precollaborative phase; 2. a 12-month quality improvement collaborative phase when hospitals implemented multiple rapid cycle tests of change and shared improvement strategies; and 3. a 12-month postcollaborative phase. Interrupted time-series models assessed the association between study phase and measure performance over time, stratified by baseline hospital performance, adjusting for seasonality and hospital fixed effects. RESULTS: Among hospitals with high baseline performance, measure scores increased during the quality improvement collaborative phase beyond the expected precollaborative trend (+0.7 points/month; 95% confidence interval, 0.4-1.0; P < .001). Among hospitals with low baseline performance, measure scores increased but at a lower rate than the expected precollaborative trend (-0.5 points/month; 95% confidence interval, -0.8 to -0.2; P < .01). CONCLUSIONS: Participation in this 8-hospital Institute for Healthcare Improvement Virtual Breakthrough Series collaborative was associated with improvement in the quality of written discharge instructions beyond precollaborative trends only for hospitals with high baseline performance.

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.

Association Between Procalcitonin and Antibiotics in Children With Community-Acquired Pneumonia.

OBJECTIVE: To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians. METHODS: We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level. RESULTS: We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions. CONCLUSION: Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship.

Associations between comorbidity-related functional limitations and pneumonia outcomes.

BACKGROUND: Underlying comorbidities are common in children with pneumonia. OBJECTIVE: To determine associations between comorbidity-related functional limitations and risk for severe pneumonia outcomes. DESIGN, SETTING, AND PARTICIPANTS: We prospectively enrolled children <18 years with and without comorbidities presenting to the emergency department with clinical and radiographic pneumonia at two institutions. Comorbidities included chronic conditions requiring daily medications, frequent healthcare visits, or which limited age-appropriate activities. Among children with comorbidities, functional limitations were defined as none or mild, moderate, and severe. MAIN OUTCOMES AND MEASURES: Outcomes included an ordinal severity outcome, categorized as very severe (mechanical ventilation, shock, or death), severe (intensive care without very severe features), moderate (hospitalization without severe features), or mild (discharged home), and length of stay (LOS). Multivariable ordinal logistic regression was used to examine associations between comorbidity-related functional limitations and outcomes, while accounting for relevant covariates. RESULTS: A cohort of 1116 children, including 452 (40.5%) with comorbidities; 200 (44.2%) had none or mild functional limitations, 93 (20.6%) moderate, and 159 (35.2%) had severe limitations. In multivariable analysis, comorbidity-related functional limitations were associated with the ordinal severity outcome and LOS (p < .001 for both). Children with severe functional limitations had tripling of the odds of a more severe ordinal (adjusted odds ratio [aOR]: 3.01, 95% confidence interval [2.05, 4.43]) and quadrupling of the odds for longer LOS (aOR: 4.72 [3.33, 6.70]) as compared to children without comorbidities. CONCLUSION: Comorbidity-related functional limitations are important predictors of disease outcomes in children with pneumonia. Consideration of functional limitations, rather than the presence of comorbidity alone, is critical when assessing risk of severe outcomes.

Influence of Immune Cell Subtypes on Mitochondrial Measurements in Peripheral Blood Mononuclear Cells From Children with Sepsis.

INTRODUCTION: Peripheral blood mononuclear cells (PBMCs) are commonly used to compare mitochondrial function in patients with versus without sepsis, but how these measurements in this mixed cell population vary by composition of immune cell subtypes is not known, especially in children. We determined the effect of changing immune cell composition on PBMC mitochondrial respiration and content in children with and without sepsis. METHODS: PBMC mitochondrial respiration and citrate synthase (CS) activity, a marker of mitochondrial content, were measured in 167 children with sepsis at three timepoints (day 1-2, 3-5, and 8-14) and once in 19 nonseptic controls. The proportion of lymphocytes and monocytes and T, B, and NK cells was measured using flow cytometry. More specific CD4+ and CD8+ T cell subsets were measured from 13 sepsis patients and 6 controls. Spearman's correlation and simple and mixed effects linear regression were used to determine the association of PBMC mitochondrial measures with proportion of immune cell subtypes. RESULTS: PBMC mitochondrial respiration and CS activity were correlated with proportion of monocytes, lymphocytes, T B, and NK cells in controls, but not in sepsis patients. PBMC mitochondrial respiration was correlated with CD4+ and CD8+ T cell subsets in both groups. After controlling for differences in immune cell composition between groups using linear regression models, PBMC respiration and CS activity remained lower in sepsis patients than controls. CONCLUSIONS: Mitochondrial measurements from PBMCs varied with changes in immune cell composition in children with and without sepsis. However, differences in PBMC mitochondrial measurements between sepsis patients and controls were at least partially attributable to the effects of sepsis rather than solely an epiphenomena of variable immune cell composition.

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.

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.