Seroprevalence of SARS-CoV-2 Among Pediatric Healthcare Workers in Spain

Spain is one of the countries most severely affected by the SARS-CoV-2 pandemic, with almost 190,000 cases as of April 18, 2020. As healthcare workers (HCW) are one of the groups hardest hit by the infection, it is important to know the seroprevalence of antibodies against SARS-CoV-2 in pediatric departments. We performed 175 immunoglobulin (Ig)M and IgG immunochromatographic rapid tests in the personnel working at the Pediatric Department of the Hospital Clinico Universitario of Santiago de Compostela (Spain), including pediatricians, residents, nurses, and other staff, on days 31-33 since the lockdown started. Seven out of the 175 tests were positive, including four for IgM and three for IgG, leading to a seroprevalence of 4.0% (95% CI: 1.1-6.9%). Only one of them had symptoms at the time of testing (sore throat). All seropositive cases yielded negative RT-PCR of the upper and lower respiratory tract. This is the first SARS-CoV-2 serological survey among HCWs reported in Spain. Notwithstanding the test limitations, our results reveal that personal protection policy and lockdown measures have been effective to limit population exposure. The low seroprevalence rate poses a significant challenge for the next strategic steps of pandemic control

Cross-sectional prevalence of SARS-CoV-2 antibodies in healthcare workers in paediatric facilities in eight countries

Funding Information: DG receives support from the NIHR Great Ormond Street Biomedical Research Centre . HZ is supported by the South African Medical Research Council . Publisher Copyright: © 2021 The Author(s)Background: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence. Aim: To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8). Methods: All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured. Findings: In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0–16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 [0.66%, 95% confidence interval (CI) 0.18–2.4] HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14–4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23–7.0) HCWs tested positive in Greece. Conclusion: Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.publishersversionPeer reviewe

Substantial burden of non-medically attended RSV infection in healthy term infants – an international prospective birth cohort study

Background: During the first year of life, one in four infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV, therefore, underrepresents the true societal burden of RSV. We assessed the burden of non-medically attended RSV infections and compared them with medically attended RSV. Methods: We performed active RSV surveillance until the age of one year in a cohort (n=993) nested within RESCEU, a prospective birth cohort study enrolling healthy term-born infants in five European countries. Parent-reported daily symptoms, medication use, wheezing and impact on family life were analyzed. Results: For 97 of 120 (80.1%) non-medically attended RSV episodes sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97), worries in 75.3% (73/97), anxiety in 34.0% (33/97), and work absenteeism in 10.8% (10/93) of episodes. Compared with medically attended RSV (n=102, 9 hospital admissions), ReSViNET severity scores were lower (3.5 vs. 4.6, p<0.001), whereas durations of respiratory symptoms and impairment of usual activities were comparable. Conclusion: Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families and society at large. These findings are important for policymakers when considering the implementation of RSV immunization in national programs

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: a multi-country prospective cohort study in Europe

Background: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Methods: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Results: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. Conclusion: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs

Low Sensitivity of BinaxNOW RSV in Infants

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Early detection of RSV can optimize clinical management and minimize use of antibiotics. BinaxNOW RSV (BN) is a rapid antigen detection test that is widely used. We aimed to validate the sensitivity of BN in hospitalized and nonhospitalized infants against the gold standard of molecular diagnosis. METHODS: We evaluated the performance of BN in infants with acute respiratory tract infections with different degrees of disease severity. Diagnostic accuracy of BN test results were compared with molecular diagnosis as reference standard. RESULTS: One hundred sixty-two respiratory samples from 148 children from October 2017 to February 2019 were studied. Sixty-six (40.7%) samples tested positive for RSV (30 hospitalizations, 31 medically attended episodes not requiring hospitalization, and 5 nonmedically attended episodes). Five of these samples tested positive with BN, leading to an overall sensitivity of BN of 7.6% (95% confidence interval [CI], 3.3%-16.5%) and a specificity of 100% (95% CI, 96.2%-100%). Sensitivity was low in all subgroups. CONCLUSIONS: We found a low sensitivity of BN for point-of-care detection of RSV infection. BinaxNOW RSV should be used and interpreted with caution

Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology

Background: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind. Methods: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. Results: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not. Conclusions: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Radon exposure and tumors of the central nervous system

Objective: To review the published evidence of links between radon exposure and central nervous system tumors through a systematic review of the scientific literature. Methods: We performed a thorough bibliographic search in Medline (PubMed) and EMBASE. We combined MeSH (Medical Subject Heading) terms and free text. We developed a purpose-designed scale to assess the quality of the included manuscripts. Results: We have included 18 studies, 8 performed on miners, 3 on the general population and 7 on children, and the results have been structured using this classification. The results are inconclusive. An association between radon exposure and central nervous system tumors has been observed in some studies on miners, but not in others. The results observed in the general adult population and in children are also mixed, with some research evincing a statistically significant association and others showing no effect. Conclusions: We cannot conclude that there is a relationship between radon exposure and central nervous system tumors. The available studies are extremely heterogeneous in terms of design and populations studied. Further research is needed in this topic, particularly in the general population residing in areas with high levels of radon. Resumen: Objetivo: Revisar la evidencia publicada entre la exposición al radón y los tumores del sistema nervioso central a través de una revisión sistemática de la literatura científica. Método: Se realiza una revisión sistemática exhaustiva de la literatura científica en Medline (PubMed) y EMBASE, combinando términos MeSH (Medical Subject Heading) y texto libre. Se desarrolla una escala específica para valorar la calidad de los estudios incluidos. Resultados: Se incluyeron 18 estudios (8 realizados en mineros, 3 en población general y 7 en niños) y los resultados se estructuraron siguiendo esa clasificación. Los resultados son inciertos. Algunos estudios en mineros han observado una asociación entre la exposición a radón y tumores del sistema nervioso central, pero otros no. Los resultados en población general adulta y en niños también son diversos, con algunas investigaciones que encuentran una asociación estadísticamente significativa y otras que no encuentran ningún efecto. Conclusiones: No puede concluirse que exista una asociación entre la exposición al radón y los tumores del sistema nervioso central. Los estudios disponibles son muy heterogéneos en cuanto al diseño y los sujetos incluidos. Es necesaria más investigación sobre este tema, en particular en población general residente en áreas con elevados niveles de radón. Keywords: Central nervous system neoplasms, Radon, Systematic review, Palabras clave: Sistema nervioso central, Radón, Revisión sistemátic

Vacunación COVID-19 en la edad pediátrica

La pandemia provocada por el virus SARSCoV-2 ha supuesto un reto global que ha cambiado nuestras vidas. La vacunación ha marcado un punto de inflexión, demostrando una elevada efectividad en la prevención de formas graves de COVID-19, fundamentalmente reduciendo hospitalización y muerte asociadas a la infección. La estrategia de vacunación en un contexto de limitación en el número de dosis disponibles ha priorizado los grupos más vulnerables y esenciales. Dado que los ni- ños no han sido un grupo especialmente afectado por la pandemia, no se contem- pla la vacunación de los mismos hasta que finalice la campaña en el resto de grupos etarios, y una vez que dispongamos de los datos adecuados de seguridad e inmuno- genicidad de la utilización de vacunas frente a COVID-19 en estas edades. Tampoco está claro cuáles son los grupos de riesgo dentro de la edad pediátrica que podrían beneficiarse. Además, los pacientes pe- diátricos no parecen actuar de reservorio como ocurre con la gripe. Algunas de las vacunas actualmente comercializadas ya han empezado a probarse en la edad pe- diátrica y se han autorizado en pacientes de 12-16 años. Se están poniendo en mar- cha en todo el mundo ensayos clínicos en población menor de 12 años para que este segmento de la población pueda vacunarse. En cualquier caso, la ansiada inmunidad de grupo frente al SARS-COV-2 pasa por la vacunación de los niños, de otro modo dejaríamos sin vacunar al 25% de la población mundial y generaríamos un reservorio especifico para la evolución del viru

Functional Inhibitory Control Dynamics in Impulse Control Disorders in Parkinson’s Disease

Published online 11 November 2019ABSTRACT: Background: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson’s disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. Methods: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. Results: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. Conclusions: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties.Basque Government. Grant Numbers: PI2016‐12, BERC 2018‐2021 Carlos III Institute of Health. Grant Numbers: PI11/02109, Rio Hortega CM16/00033 ERA‐Neuron program. Grant Number: PIM2010ERN‐00733 Spanish Ministry of Economy and Competitiveness (MINECO). Grant Numbers: PGC2018‐093408‐B‐I00, RYC‐2014‐15440, SEV‐2015‐049