Changing Characteristics of Children With COVID-19 in Colorado Admitted During Different Variant Periods.

BACKGROUND: Data are lacking on the impact of different severe acute respiratory syndrome coronavirus 2 variants in children and on pediatric vaccine effectiveness. We examined differences among children requiring hospital admission associated with coronavirus disease 2019 (COVID-19) during wild type, Delta and Omicron variant periods and calculated vaccine effectiveness at preventing symptomatic hospitalization during the Delta and Omicron variant periods. METHODS: We conducted a retrospective review of children younger than 21 years of age hospitalized with symptomatic COVID-19. Characteristics were compared between variant periods using Kruskal-Wallis or generalized Fisher exact tests. We estimated vaccine effectiveness in preventing symptomatic hospitalization. RESULTS: We included 115 children admitted during the wild type period, 194 during Delta and 226 during the Omicron periods. Median age (years) decreased (12.2 wild type, 5.9 Delta, 1.3 Omicron periods, P < 0.0001) over time. Children were less likely to have a comorbid condition, including diabetes or obesity, and had shorter admissions during Omicron compared with the wild type and Delta periods. Intensive care unit admissions and respiratory support requirements were highest during the Delta period ( P = 0.05). Among children ≥12 years, adjusted vaccine effectiveness at preventing symptomatic hospitalization was 86% during Delta and 45% during Omicron periods. CONCLUSIONS: Children hospitalized with COVID-19 during later variant periods were younger and less likely to have comorbidities. Children admitted during the Delta variant period required more intensive care and respiratory support compared to other variant periods. Vaccination was less effective at preventing symptomatic hospital admission during the Omicron period compared to the Delta period.

Metagenomic Next-Generation Sequencing for Diagnosis of Pediatric Meningitis and Encephalitis: A Review.

Metagenomic next-generation sequencing is a novel diagnostic test with the potential to revolutionize the diagnosis of pediatric meningitis and encephalitis through unbiased detection of bacteria, viruses, parasites, and fungi in cerebrospinal fluid. Current literature is mostly observational with variable indications, populations, and timing of testing with resulting variability in diagnostic yield and clinical impact. Diagnostic stewardship strategies are needed to direct testing toward high-impact pediatric populations, to optimize timing of testing, to ensure appropriate interpretation of results, and to guide prompt optimization of antimicrobials. This review highlights the high clinical potential of this test, though future studies are needed to gather clinical impact and cost-effectiveness data for specific indications in pediatric populations.

Antimicrobial Resistance Trends at a Pediatric Hospital in Guatemala City, 2005-2019.

Antimicrobial resistance (AMR) is increasing worldwide. We analyzed AMR rates for bacterial species identified from pediatric blood cultures between 2005 and 2019 at a single institution in Guatemala. We found significantly increased rates in Gram-negative resistance, with a high prevalence of carbapenem-resistant Acinetobacter and Klebsiella harboring the New Delhi metallo-beta-lactamase gene.

Clinical Impact of the Expanded BioFire Blood Culture Identification 2 Panel in a U.S. Children's Hospital.

The BioFire blood culture identification (BCID) panel decreases time to pathogen identification and time to optimal antimicrobial therapy. The BioFire blood culture identification 2 (BCID2) panel is an expanded panel with 17 additional targets and resistance genes; however, there are limited data on its impact in pediatric patients. We compared the BioFire BCID2 panel and the BCID panel by assaying BCID2 simultaneously with the current standard of care on 191 consecutive blood culture specimens at Children's Hospital Colorado. The primary outcome was equivalence, measured as percent agreement between the two panels and standard culture. The theoretical reduction in time to optimal therapy was calculated overall, with subanalyses performed on Enterococcus species and Gram-negative resistance genes. The percent agreement was equivalent between the two panels, with BCID at 98% (95% confidence interval [CI], 95 to 100%) and BCID2 at 97% (95% CI, 93 to 99%); the difference was 1.2% (95% CI, -0.8, 3.1%; P < 0.0001). There was not a significant reduction in time to theoretical optimal therapy with BCID2 compared to BCID for all cultures (reduction of 9 h, P = 0.3). Notably, 13 Enterococcus faecalis isolates were detected on BCID2, which would have resulted in a theoretical reduction in time to optimal antimicrobial therapy of 34 h (P = 0.0046). Five CTX-M genes were detected for enteric bacteria. The BioFire BCID2 panel had equal rates of detection compared to the BioFire BCID panel in pediatric patients. It had the advantage of detecting more organisms at the species level, and significantly reducing time to theoretical optimal antimicrobial therapy for Enterococcus faecalis. With the additional resistance genes, it also has the potential to impact care with earlier identification of resistant enteric pathogens. IMPORTANCE The BioFire BCID2 panel is an accurate panel that is equivalent to the BioFire BCID panel compared to standard culture. The BioFire BCID2 panel offers several advantages over the BioFire BCID panel, including enterococcal species identification, Gram-negative resistance gene detection, Salmonella identification, and the added mecA/mecC and SCCmec right extremity junction (MREJ) target for better Staphylococcus aureus and coagulase-negative Staphylococcus (CoNS) differentiation. Most importantly, it provides additional clinical impact with the potential to decrease the time to optimal antimicrobial therapy compared to the BioFire BCID panel, with likely further impact at institutions with a higher prevalence of Gram-negative resistance.

Risk Factors for Severe COVID-19 in Children.

BACKGROUND: There are limited pediatric data regarding severe COVID-19 disease. Our study aims to describe the epidemiology and identify risk factors for severe COVID-19 disease in children. METHODS: This is a retrospective cohort study among children with positive SARS-CoV-2 PCR from March to July 2020 at Children's Hospital Colorado. Risk factors for severe disease were analyzed as defined by hospital admission, respiratory support, or critical care. Univariable and multivariable analyses were conducted. RESULTS: Among 454 patients identified with SARS-CoV-2, 191 (42.1%) were females, median age 11 years. Fifty-five percent of all patients identified as Hispanic compared with 29% among all hospital visits in 2019 (P < 0.0001). In multivariable analyses, age 0-3 months or >20 years [adjusted odds ratio (aOR), 7.85; P < 0.0001 and aOR, 5.1; P = 0.03, respectively], preterm birth history (aOR, 3.7; P = 0.03), comorbidities [including immunocompromise (aOR, 3.5; P = 0.004), gastrointestinal condition (aOR, 2.7; P = 0.009), diabetes (aOR, 6.6; P = 0.04), asthma (aOR, 2.2; P = 0.04)], and specific symptoms at presentation were predictors for admission. Age 0-3 months or >20 years, asthma, gastrointestinal condition, and similar symptoms at presentation were also predictors for respiratory support. Elevated C-reactive protein was associated with the need for critical care with median of 17.7 mg/dL (IQR, 5.3-22.9) versus 1.95 mg/dL (IQR, 0.7-5.5) among patients requiring critical versus no critical care (OR, 1.2; P = 0.02). CONCLUSIONS: Extremes of age, comorbid conditions, and elevated CRP are predictors of severe disease in children. Findings from this study can inform pediatric providers and public health officials to tailor clinical management, pandemic planning, and resource allocation.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Fetal programming of adrenal PNMT and hypertension by glucocorticoids in WKY rats is dose and sex-dependent.

Biochemical changes in utero may alter normal fetal development, resulting in disease later in life, a phenomenon known as fetal programming. Recent epidemiological studies link fetal programming to negative health outcomes, such as low birth weight and hypertension in adulthood. Here, we used a WKY rat model and studied the molecular changes triggered by prenatal glucocorticoid (GC) exposure on the development of hypertension, and on the regulation of phenylethanolamine N-methyl transferase (PNMT), the enzyme responsible for biosynthesis of epinephrine, and a candidate gene linked to hypertension. Clinically, high doses of the synthetic GC dexamethasone (DEX) are used to treat infant respiratory distress syndrome. Elevated maternal GCs have been correlated with fetal programming of hypertension. The aim of this study was to determine if lower doses of DEX would not lead to detrimental fetal programming effects such as hypertension. Our data suggests that prenatal stress programs for increased expression of PNMT and altered regulation of PNMT in males and females. Importantly, we identified that DEX mediated programming was more apparent in the male rats, and the lower dose 10µg/kg/day of DEX did not lead to changes in blood pressure (BP) in female rats suggesting that this dose is below the threshold for programming of hypertension. Furthermore, sex-specific differences were observed in regards to programming mechanisms that may account for hypertension in males.

Phenylethanolamine N-methyltransferase gene expression in adrenergic neurons of spontaneously hypertensive rats.

Epinephrine is synthesised by the catecholamine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), primarily in chromaffin cells of the adrenal medulla and secondarily in brainstem adrenergic neurons of the medulla oblongata. Epinephrine is an important neurotransmitter/neurohormone involved in cardiovascular regulation; however, overproduction is detrimental with negative outcomes such as cellular damage, cardiovascular dysfunction, and hypertension. Genetic mapping studies have linked elevated expression of PNMT to hypertension. Adrenergic neurons are responsible for blood pressure regulation and are the only PNMT containing neurons in the brainstem. The purpose of the current study was to determine whether elevated blood pressure found in adult spontaneously hypertensive rats (SHR) is associated with altered regulation of the PNMT gene in catecholaminergic neurons. C1, C2, and C3 adrenergic regions of 16 week old Wistar Kyoto (WKY) and SHR rats were excised using micropunch microdissection for mRNA expression analyses. Results from the current study confirm high PNMT mRNA expression in all three brainstem adrenergic regions (C1: 2.96-fold; C2: 2.17-fold; C3 1.20-fold) of the SHR compared to normotensive WKY rats. Furthermore, the immediate early gene transcription factor (Egr-1) mRNA was elevated in the C1 (1.84-fold), C2 (8.57-fold) and C3 (2.41-fold) regions in the brainstem of the SHR. Low mRNA expression for transcription factors Sp1 and GR was observed, while no change was observed for AP-2. The findings presented propose that alterations in the PNMT gene regulation in the brainstem contribute to enhanced PNMT production and epinephrine synthesis in the SHR, a genetic model of hypertension.