COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit

Identifying predictors of interferon-gamma release assay results in pediatric latent tuberculosis: a protective role of BCG?

Rationale: Interferon-gamma release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. Objectives: To investigate factors influencing results of interferon gamma release assays in children using a large European dataset. Methods: The Pediatric Tuberculosis Network European Trials group pooled and analysed data from five sites across Europe comprising 1128 children who were all investigated for latent tuberculosis infection by using TST and at least one interferon-gamma release assay. Multi-variate analyses examined age, Bacille Calmette-Guérin (BCG) vaccination status, and gender as predictor variables of results. Subgroup analyses included children who were household contacts. Measurements and results:1,093 children had a Quantiferon Gold In-Tube and 382 had a T-SPOT.TB interferon gamma release assay. Age was positively correlated with a positive blood result (Quantiferon Gold In-Tube: OR=1.08 per year increasing age, p&lt;0.0001; T-SPOT.TB: OR=1.14 per year increasing age, p&lt;0.001). 5.5% of children with a tuberculin skin test result &lt;5mm, 14.8% if &lt;10mm, and 23.9% if &lt;15mm, had a positive Quantiferon Gold In-Tube result. Prior BCG vaccination was associated with a negative interferon gamma release assay result (Quantiferon Gold In-Tube: OR=0.41, p&lt;0.001; T-SPOT.TB: OR=0.41, p&lt;0.001). Young age was a predictor of indeterminate IGRA, but indeterminate rates were low (3.6% in &lt;5years, 1% in &gt;5 years). Conclusions: Our data show BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of interferon-gamma release assays to children with positive skin tests risks underestimating latent infection

Tuberculosis in Adolescents in Bulgaria for a Three-Year Period: 2018&ndash;2020

Background: Each year, approximately two million adolescents and young adults in the world become infected with tuberculosis (TB). The problem is that the classification of the disease includes children in the age group 0&ndash;14 years and young adults aged 15 and over. The present study aims to analyze and compare the epidemiology and clinical presentation of TB in Bulgaria in the different age subgroups of childhood. Methods: A retrospective study was undertaken of the newly diagnosed children (n = 80) with TB treated onsite from January 2018 to December 2020 at the Multiprofile Hospital for Active Treatment of Pulmonary Diseases (&ldquo;St. Sofia&rdquo;). They were distributed into three age groups: aged 8&ndash;11 (prepuberty), aged 12&ndash;14 (younger adolescents), and aged above 15 (older adolescents). Results: A clear finding of the research indicated that adolescent children develop TB both as primary and secondary infections. In a large number of cases with the children under our care, we found enlarged intrathoracic lymph nodes as well as infiltrative changes in the lungs, i.e., we observed transitional forms. There were statistically significant differences between the age group &gt;15 years old and each of the other two younger groups for diagnosis, the severity of intoxication, and BK spreading status. Conclusion: The course of tuberculosis in adolescence has its own specifics and differences between the three age groups in the current study

Surgical Treatment of Lung Abscess Due to an Awn Aspiration in a 9-Year-Old Child: A Case Report

Introduction: Foreign body aspiration is a common condition in the child population and is one of the leading causes of accidental deaths in children. The aspiration of an awn (grass inflorescences) is extremely rare. Aim of the study: This study aims to describe the symptoms, diagnosis, therapeutic difficulties, and results of the aspiration of grass inflorescence. They are all related to the shape of the awn’s head and its behavior in the tracheobronchial tree. Case description: We present a 9-year-old boy with a history of an awn aspiration and recurrent respiratory infections. After antibiotic and symptomatic treatment, two bronchoscopies were performed, and both showed stenosis and obturation of the segmental and subsegmental bronchi of the left posterior basal segment, but no foreign body was found. After recanalization and continuous medicamentous treatment, a computed tomography (CT) verified the lung abscess. Video-assisted thoracoscopic surgery (VATS) was performed, and an atypical lung resection was conducted. During the surgery, a foreign body—grass inflorescence from the species Hordeum murinum—was found in the resected tissue. The patient recovered uneventfully after the surgery. Conclusions: Grass inflorescence aspiration in the child population is an extremely rare event, and it represents a diagnostic and therapeutic issue. The exact timing of surgery is very important to reduce complications and avoid death

European shortage of purified protein derivative and its impact on tuberculosis screening practices

Setting: in June 2014, we became aware that shortages of purified protein derivative (PPD), the test substance used for the tuberculin skin test (TST), had occurred in several European health care institutions providing care for children with tuberculosis (TB).Objective: to establish the extent of the shortage, a survey was performed.Design: survey conducted over a 1-month period (June–July 2014) among members of the Paediatric Tuberculosis Network European Trials Group (ptbnet).Results: thirty-five physicians from 23 European countries contributed data. The most commonly used PPD product was RT23 (Statens Serum Institut; n = 22, 63%). Twenty-one (60%) participants reported that their institution was experiencing a PPD shortage. The majority (n = 17, 81%) of those reporting a shortage were using RT23. Thirteen (37%) participants reported changes in screening practices resulting from the shortage, including sourcing PPD from alternative manufacturers, restricting remaining supplies to patients at greatest risk or replacing TST by an interferon-gamma release assay.Conclusions: the data show that a PPD shortage occurred in 2014, affecting multiple European countries. The shortage resulted in changes in TB screening capabilities and practices, potentially compromising both patient care as well as public health efforts. Appropriate actions to prevent future PPD shortages should be explored urgently by public health agencies and key stakeholder

Treatment and outcome in children with tuberculous meningitis - a multi-centre Paediatric Tuberculosis Network European Trials Group study.

INTRODUCTION: Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings. METHODS: Multicentre, retrospective study involving 27 paediatric healthcare institutions in nine European countries via an established paediatric TB research network, before and after the 2014 revision of WHO dosing recommendations. RESULTS: Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard four-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (IQR 4.5-21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of one or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention and mechanical ventilation as risk factors for unfavourable outcome. DISCUSSION: There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future

Treatment and outcome in children with tuberculous meningitis - a multi-centre Paediatric Tuberculosis Network European Trials Group study.

INTRODUCTION Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings. METHODS Multicentre, retrospective study involving 27 paediatric healthcare institutions in nine European countries via an established paediatric TB research network, before and after the 2014 revision of WHO dosing recommendations. RESULTS Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard four-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (IQR 4.5-21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of one or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention and mechanical ventilation as risk factors for unfavourable outcome. DISCUSSION There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future