Antibiotic Prescribing in Children Hospitalized With COVID-19 and Multisystem Inflammatory Syndrome in Spain: Prevalence, Trends, and Associated Factors.

The SARS-CoV-2 pandemic has caused an increase in antibiotic use in different settings. We describe the antibiotic prescribing prevalence, associated factors and trends, as well as concomitant bacterial infections in children hospitalized with COVID-19 or multisystemic inflammatory syndrome related to SARS-CoV-2 in Spain.

Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children.

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection.

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

Changes in body composition and cardiometabolic risk factors in relation to the reduction in body mass index in adolescents with obesity.

Introduction: Introduction: there are controversial data in relation to the reduction in body mass index standard deviation score (BMI-SDS) needed to improve adiposity in the pediatric population with obesity. The aim of this work was to determine the minimum variation in BMI-SDS required to improve the values of adiposity markers and cardiometabolic risk factors in growing adolescents with obesity. Methods: a longitudinal study consisting of clinical evaluation (waist circumference, waist-to-height ratio, fat mass index, and blood pressure) and blood testing (insulin resistance and lipid profile) was conducted in 350 adolescents with obesity (152 boys and 198 girls) aged 10.2-14.3 years who went through a combined intervention (12 months). Results: a decrease in SDS-BMI ≤ 0.5 was not associated with any significant improvement in the clinical features and blood testing recorded. A decrease in BMI-SDS > 0.5, and especially if > 1.0, was linked to a significant improvement in adiposity markers. A decrease in BMI-SDS > 0.5 was associated with a significant improvement in insulin resistance, and a decrease in BMI-SDS > 1.0 was associated with a significant decrease in the percentage of patients who showed high values of systolic blood pressure, HOMA-IR, and lipid profile Conclusions: improvement in body composition, insulin resistance, and lipid profile can be observed with reductions in BMI-SDS ≥ 0.5 in obese adolescents, while extended benefits are obtained by losing at least 1.0 BMI-SDS.

Introducción: Introducción: los datos en relación con la reducción del índice de masa corporal (IMC-SDS) necesario para mejorar la adiposidad en la población pediátrica con obesidad son controvertidos. El objetivo de este trabajo es determinar la variación mínima del IMC-SDS necesaria para mejorar los valores de los marcadores de adiposidad y los factores de riesgo cardiometabólico en adolescentes obesos. Métodos: estudio longitudinal clínico (perímetro de cintura, índice cintura-estatura e índice de masa grasa y presión arterial) y analítico (HOMA-R y perfil lipídico) realizado en 350 adolescentes con obesidad (152 niños y 198 niñas) de entre 10,2 y 14,3 años de edad que completaron una intervención combinada (12 meses). Resultados: una disminución en el índice de masa corporal (SDS-BMI) ≤ 0,5 no se asoció con ninguna mejora significativa de las características clínicas y analíticas registradas. Una disminución del IMC-SDS > 0,5, y especialmente si > 1,0, se relacionó con una mejora significativa de los marcadores clínicos de adiposidad. Una disminución del IMC-SDS > 0,5 se asoció con una mejora significativa de la resistencia a la insulina y una disminución del BMI-SDS > 1,0 se asoció con una disminución significativa del porcentaje de pacientes que mostraban valores altos de presión arterial sistólica, HOMA-IR y perfil lipídico Conclusiones: con una reducción del IMC-SDS ≥ 0,5 se observa una mejoría tanto en la composición corporal como en los factores de riesgo cardiovascular en los adolescentes obesos; no obstante, estos beneficios son mayores si la reducción del IMC-SDS es superior a 1.0.

A Bayesian Model to Predict COVID-19 Severity in Children.

BACKGROUND: We aimed to identify risk factors causing critical disease in hospitalized children with COVID-19 and to build a predictive model to anticipate the probability of need for critical care. METHODS: We conducted a multicenter, prospective study of children with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care. We used a multivariable Bayesian model to estimate the probability of needing critical care. RESULTS: The study enrolled 350 children from March 12, 2020, to July 1, 2020: 292 (83.4%) and 214 (73.7%) were considered to have relevant COVID-19, of whom 24.2% required critical care. Four major clinical syndromes of decreasing severity were identified: multi-inflammatory syndrome (MIS-C) (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome (19.6%). Main risk factors were high C-reactive protein and creatinine concentration, lymphopenia, low platelets, anemia, tachycardia, age, neutrophilia, leukocytosis, and low oxygen saturation. These risk factors increased the risk of critical disease depending on the syndrome: the more severe the syndrome, the more risk the factors conferred. Based on our findings, we developed an online risk prediction tool (https://rserver.h12o.es/pediatria/EPICOAPP/, username: user, password: 0000). CONCLUSIONS: Risk factors for severe COVID-19 include inflammation, cytopenia, age, comorbidities, and organ dysfunction. The more severe the syndrome, the more the risk factor increases the risk of critical illness. Risk of severe disease can be predicted with a Bayesian model.

Chest radiograph in hospitalized children with COVID-19. A review of findings and indications.

PURPOSE: Many articles have been published regarding chest-imaging in COVID-19, but fewer studies have been published in pediatric populations. COVID-19 symptoms in children are generally milder and radiological tests have fewer positive findings. Indications for chest imaging in pediatric COVID-19 patients remain unclear. This study aims to describe the chest radiographs performed in COVID-19 patients in a pediatric hospital, to review the current chest X-ray indications and to develop an specific age-adjusted protocol for chest-imaging in children with COVID-19. METHODS: Retrospective study in hospitalized pediatric COVID-19 patients in Navarre, Spain. Between March and December 2020, 44 children were included (mean age 3.8-year-old, 50 % males). Demographic information, cause of admission, symptoms, and clinical evolution were described. Chest imaging technique performed, indications and findings were analyzed. A literature review was performed searching for current COVID-19 pediatric chest-imaging indications. RESULTS: Chest X-rays were performed in 35 patients (80 % of admissions) and most common indications were fever and respiratory symptoms. 53 % of the chest X-rays were considered "normal" and the classical bilateral diffuse interstitial pattern, described in adults, was only present in 22 %. All patients with pathological chest X-rays were symptomatic and reported fever (100 %) and fever tended to be longer (fever duration: 4.25 vs. 2.46 days p:0.048) in patients with pathological radiographs. We present a specific protocol for chest-imaging in pediatric COVID-19 cases. CONCLUSIONS: COVID-19 clinical manifestations and radiological findings are milder and less specific in children. Imaging should not be used as a screening tool or a routine complementary test in pediatric COVID-19 patients, not even in hospitalized cases.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

SARS-CoV-2 infection in children requiring hospitalization: the experience of Navarra, Spain.

BACKGROUND: Coronavirus disease 2019 in children, or pediatric COVID-19, initially was described as an acute respiratory syndrome similar to the adult presentation but with less severe manifestations. METHODS: We describe the clinical characteristics, disease presentation, treatments and outcomes of all pediatric cases with COVID-19 admitted to the reference hospitals in Navarra, Spain during the first wave of the COVID-19 outbreak (February-May 2020). RESULTS: We found a low number of hospitalized cases in infants and children compared to adults with a hospitalization ratio of 1:180. Most of these hospitalized cases did not suffer from severe disease. Over 80% of infections reported household contacts, and the mother was the known-contact in 83% of these cases. 72% of hospitalized cases were previously healthy children. We describe how symptoms in pediatric cases are nonspecific and how COVID-19 can be presented with a wide range and variety of symptoms. Respiratory symptoms are not always present, and severe neurological and cardiac features can occur in previously healthy children. CONCLUSION: Epidemiological description and case reports will be key to a better recognition and to adequate treatment of pediatric patients with COVID-19.

Reference values of fat mass index and fat-free mass index in healthy Spanish adolescents.

INTRODUCTION: Introduction: body mass index (BMI) does not allow to discriminate the composition of the different body compartments. The aim of this study was to develop reference values for the fat mass index (FMI) and fat-free mass index (FFMI) in healthy adolescents using anthropometric techniques in order to provide reference standards for daily clinical practice. Methods: a cross-sectional study in 1,040 healthy Caucasian adolescents (470 boys and 570 girls) aged 10.1 to 14.9 years. Weight, height, and skinfold thickness were recorded, and BMI, percentage of total body fat, FMI and FFMI, and FMI and FFMI percentiles were calculated. Results: FFMI and FMI percentiles for healthy adolescents (both sexes) categorized by age are displayed. In boys a significant increase in FFMI is observed, and both the percentage of total body fat and FMI significantly decreased. In contrast, in girls the percentage of body fat mass, FMI, and FFMI significantly increased. Except at 10 years of age, FMI was higher (p < 0.05) in girls at all ages. FFMI was higher (p < 0.05) in boys at all ages. Conclusions: reference values of FMI and FFMI would be a very useful instrument in clinical practice for the diagnosis and, especially, the analysis of body composition changes during the treatment of childhood obesity.

INTRODUCCIÓN: Introducción: el índice de masa corporal (IMC) no permite discriminar la composición proporcional de los distintos compartimentos corporales. El objetivo de este estudio fue elaborar tablas del índice de masa grasa (IMG) y de masa libre de grasa (IMLG) a partir de la medida de los pliegues cutáneos, para que sirvan como patrones de referencia de los adolescentes sanos de ambos sexos. Material y métodos: estudio transversal de 1040 adolescentes caucásicos sanos (470 varones y 570 mujeres) de entre 10,1 y 14,9 años de edad. Se registraron el peso, la talla y el grosor del pliegue cutáneo, y se calcularon el IMC, el porcentaje de grasa total, el IMG, el IMLG y los percentiles del IMG e IMLG. Resultados: se exponen los valores medios del IMG y el IMLG con su distribución percentilada en ambos sexos. En los varones aparece un incremento (p < 0,05) del IMLG con la edad, mientras que el porcentaje de grasa total y el IMG desminuyen (p < 0,05). En cambio, en las mujeres, el porcentaje de grasa total, el IMG y el IMLG se incrementan (p < 0,05) con la edad. Salvo a la edad de 10 años, el IMG fue superior (p < 0,05) en las mujeres de todas las edades, mientras que el IMLG fue superior (p < 0,05) en los varones de todas las edades. Conclusión: los valores de referencia del IMG y el IMLG podrían ser un instrumento útil en la práctica clínica para el diagnóstico y, especialmente, el análisis de los cambios de la composición corporal durante el tratamiento de la obesidad infantil.

Case Report: Benign Infantile Seizures Temporally Associated With COVID-19.

Background: Non-febrile illness seizures may present in previously healthy children as afebrile seizures associated with minor infections, such as mild gastroenteritis or respiratory tract infections, and are linked to a genetic predisposition. For the novel human coronavirus SARS-CoV-2, causing COVID-19, fever, cough, and gastrointestinal complaints are the most common symptoms in children, and a hyperimmune response may be present. No detailed temporally associated neurological complications have been documented in pediatric case series so far. Case description: We present the case of a 3-months-old girl with non-febrile repeated seizures in a COVID-19 family setting. The infant started with a mild fever and cough that lasted for 2 days. At day 6 from onset, the girl presented with two focal motor seizures with impaired consciousness and awareness. All investigations ruled out signs of meningo-encephalitis or active epilepsy, including normal electroencephalogram and cerebral magnetic resonance imaging. PCR from nasal and throat swabs was positive for SARS-CoV-2. Remarkably, blood ferritin and D-dimer levels were increased. At day 9, the infant presented another afebrile motor seizure, and levetiracetam dose was modified there was a favorable response within 3 months of the follow-up. Much interest has been raised with regards to host genetic determinants to disease severity and susceptibility to COVID-19. We thus performed whole exome sequencing, revealing a pathogenic frameshift mutation in the PRRT2 gene in both the mother and the infant. The mother had presented two late infantile febrile convulsions with normal outcome afterwards. Discussion: The hyperimmune response described in adult cases with COVID-19 can be seen in infants, even in the absence of respiratory symptoms. Moreover, COVID-19 may present in infants as non-febrile seizures, triggering early onset seizures in infants with a genetic predisposition. In this pandemic situation, precision medicine using massive sequencing can shed light on underlying molecular mechanisms driving the host response to COVID-19.

Effects of the application of a prolonged combined intervention on body composition in adolescents with obesity.

BACKGROUND: The aim of this study is to describe the effects of a prolonged dietary-behavioral-physical activity intervention (24 months) on body composition in a group of adolescents with obesity. METHODS: Longitudinal study in 196 individuals with obesity (86 boys and 110 girls) aged 10.1-14.9 years that completed a prolonged combined intervention (24 months). Values for weight, height, skinfold thickness, waist circumference, BMI, body fat, fat mass index (FMI) and fat-free mass index (FFMI) were registered or calculated. A good response to treatment was reported when a BMI z-score reduction of greater than or equal to 0.5 units of the initial value occurred after 24 month of follow up. RESULTS: A good response after 24 months of follow-up reached 58.2% (n = 114). In boys with obesity and BMI status improvement, weight z-score, BMI z-score, body fat, and FMI significantly decreased (p < 0.05). In girls with obesity and BMI status improvement, weight z-score, BMI z-score, waist circumference, waist z-score, body fat and FMI significantly decreased (p < 0.05). In both sexes the height and FFMI increased significantly (p < 0.05). The multiple logistic regression analysis showed that girls and younger age were associated with BMI status improvement; concurrently, the place of residence (urban or rural) and degree of obesity were not associated with BMI status improvement. CONCLUSION: The application of long-term combined strategies in the treatment of childhood obesity seems to be effective. As BMI decreases, a reduction in fat mass is also detected, with evident sexual dimorphism, in the absence of changes in fat-free mass and, consequently, in longitudinal growing.

Hypovitaminosis D and Cardiometabolic Risk Factors in Adolescents with Severe Obesity.

BACKGROUND/OBJECTIVES: Obesity is associated with cardiometabolic risk factors and with Vitamin D deficiency. The aim of this study was to examine the relationship between 25(OH)D concentrations and cardiometabolic risk factors in adolescents with severe obesity. SUBJECTS/METHODS: A cross-sectional clinical assessment (body mass index, fat mass index, fat-free mass index, waist-to-height ratio, and blood pressure) and metabolic study (triglycerides, total cholesterol, HDL-C, LDL-C, glucose, insulin, HOMA-IR, leptin, calcium, phosphorous, calcidiol, and PTH) were carried out in 236 adolescents diagnosed with severe obesity (BMI z-score > 3.0, 99th percentile), aged 10.2-15.8 years. The criteria of the US Endocrine Society were used for the definition of Vitamin D status. RESULTS: Subjects with Vitamin D deficiency had significantly elevated values (p < 0.05) for BMI z-score, waist circumference, waist z-score, body fat percentage, fat mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, LDL-C, insulin, HOMA-IR, leptin, and PTH than subjects with normal Vitamin D status. There was a significant negative correlation (p < 0.05) of serum 25(OH)D levels with body fat percentage, FMI, systolic BP, total cholesterol, triglyceride, LDL-C, glucose, insulin, HOMA-IR, leptin, and PTH. CONCLUSIONS: Low Vitamin D levels in adolescents with severe obesity were significantly associated with some cardiometabolic risk factors, including body mass index, waist circumference, fat mass index, high blood pressure, impaired lipid profile, and insulin resistance.

Assessment of vitamin D status and parathyroid hormone during a combined intervention for the treatment of childhood obesity.

BACKGROUND: Obesity is associated with vitamin D deficiency. The aim of this work is to analyze the changes in vitamin D status and PTH levels in a group of children with obesity receiving combined intervention program in order to get BMI status reduction. METHODS: Longitudinal study in 119 children with obesity, aged 9.1-13.9 years, included in a 1-year combined dietary-behavioral-physical activity intervention. Anthropometric measurements (weight, height, BMI and fat mass index) were registered every 3 months and blood testing (calcium, phosphorous, 25(OH)D and PTH) were collected at the beginning and after 12 months of follow-up. A control group was recruited (300 healthy children, aged 8.1-13.9 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. RESULTS: Vitamin D deficiency was significantly higher in obesity group (31.1 vs. 14%). There was negative correlation between 25(OH)D and fat mass index (r = -0.361, p = 0.001). Patients with BMI reduction throughout combined intervention were 52 (43.7%). There was a significant increase in the prevalence of hypovitaminosis D in patients without BMI reduction at the end of follow-up, but in those patients with BMI reduction there was no changes of vitamin D status. CONCLUSIONS: Obesity increases the prevalence of suboptimal vitamin D status, and a BMI status reduction in children with obesity may be required to at least stabilize vitamin D status.

Assessment of body composition changes during a combined intervention for the treatment of childhood obesity.

OBJECTIVE: One of the main objectives in the treatment of childhood obesity is to reduce the percentage of body fat mass without negatively affecting fat-free mass (FFM) and, consequently, longitudinal growth. The aim of this study was to analyze the changes that take place in body compartments in a group of patients with obesity under combined treatment. METHODS: This was a longitudinal study with 109 children with obesity 9.1 to 13.9 y of age included in a combined dietary-behavioral-physical activity intervention. Weight, height, skinfold thickness, and waist circumference were registered, and body mass index (BMI), fat mass index (FMI), FFM and waist-to-height ratio (WHR) were calculated over a period of 12 mo. The BMI z-score allowed us to establish two groups: obesity (n = 50) and severe obesity (n = 59). A nutritional improvement was considered when a decrease of BMI z-score of the initial value occurred after 12 mo of follow-up. RESULTS: The improvement in nutritional status reached 61.5% (n = 67). In the obesity group with nutritional improvement (n = 32), FMI significantly decreased (P < 0.005) and there were no significant differences in weight, height z-score, FFM, and WHR throughout the combined intervention. In the severe obesity group with nutritional improvement (n = 35), there were no significant differences in weight, height z-score, FMI, FFM, and WHR throughout combined intervention. CONCLUSIONS: Maintaining a constant weight in the mid- to long term to improve nutritional status would be adequate in children with infantile-juvenile obesity. However, maintaining a steady weight would not be sufficient for those patients diagnosed with severe obesity.