Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.

A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.

BACKGROUND: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. METHODS: We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. FINDINGS: Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. INTERPRETATION: A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers.

BACKGROUND: Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19. METHODS: An observational study including 182 children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children was performed in Buenos Aires, Argentina. Neutrophil phenotype was analyzed by flow cytometry in blood samples. Cytokine production, plasma levels of IgG antibodies directed to the spike protein of SARS-CoV-2 and citrullinated histone H3 were measured by ELISA. Cell-free DNA was quantified by fluorometry. FINDINGS: Compared with healthy controls, neutrophils from children with COVID-19 showed a lower expression of CD11b, CD66b, and L-selectin but a higher expression of the activation markers HLA-DR, CD64 and PECAM-1 and the inhibitory receptors LAIR-1 and PD-L1. No differences in the production of cytokines and NETs were observed. Interestingly, the expression of CD64 in neutrophils and the serum concentration of IgG antibodies directed to the spike protein of SARS-CoV-2 distinguished asymptomatic from mild and moderate COVID-19. INTERPRETATION: Acute lung injury is a prominent feature of severe COVID-19 in adults. A low expression of adhesion molecules together with a high expression of inhibitory receptors in neutrophils from children with COVID-19 might prevent tissue infiltration by neutrophils preserving lung function. FUNDING: This study was supported by the Ministry of Science and Technology (National Agency for Scientific and Technological Promotion, IP-COVID-19-0277 and PMO BID PICT 2018-2548), and University of Buenos Aires from Argentina (20020170100573BA).

Especialidad de Emergentología Pediátrica: ¡Bienvenida! / Pediatric emergency medicine specialty: Welcome!

La Emergentología Pediátrica se ha desarrollado en el mundo como una subespecialidad de la pediatría durante las últimas décadas. Los registros muestran una creciente necesidad de sus servicios. Esta orientación tuvo su empuje inicial en Estados Unidos de América y nuestro país ha continuado por el mismo camino, así como muchos otros países latinoamericanos. Aun así, habrá que intensificar su promoción y trabajar en el desarrollo de la investigación y la docencia relacionadas con el área para promover el bienestar de los niños, sus familias y de la sociedad en general.

Pediatric Emergency Medicine has developed around the world as a subspecialty of pediatrics. There is plenty of data reflecting a growing need for its services. The subspecialty was initiated in the United States and Argentina, together with other Latin American countries, followed the same path. Nevertheless, there is yet much to be done. It is necessary to strengthen its promotion and to stimulate research and teaching activities in order to continue improving the quality of care delivered to the pediatric population, their families and society as a whole.

[Pediatric emergency medicine specialty: Welcome!] / Especialidad de Emergentología Pediátrica: ¡Bienvenida!

Pediatric Emergency Medicine has developed around the world as a subspecialty of pediatrics. There is plenty of data reflecting a growing need for its services. The subspecialty was initiated in the United States and Argentina, together with other Latin American countries, followed the same path. Nevertheless, there is yet much to be done. It is necessary to strengthen its promotion and to stimulate research and teaching activities in order to continue improving the quality of care delivered to the pediatric population, their families and society as a whole.

La Emergentología Pediátrica se ha desarrollado en el mundo como una subespecialidad de la pediatría durante las últimas décadas. Los registros muestran una creciente necesidad de sus servicios. Esta orientación tuvo su empuje inicial en Estados Unidos de América y nuestro país ha continuado por el mismo camino, así como muchos otros países latinoamericanos. Aun así, habrá que intensificar su promoción y trabajar en el desarrollo de la investigación y la docencia relacionadas con el área para promover el bienestar de los niños, sus familias y de la sociedad en general.

Síndrome de desgaste profesional (burnout) en médicos de unidades de cuidados intensivos pediátricos en la Argentina / Physician's burnout in pediatric intensive care units from Argentina

Introducción. En la actualidad hay escasez de médicos en unidades de cuidados intensivos pediátricos (UCIP). La causa de este déficit es multifactorial, pero el "fenómeno de burnout" o agotamiento profesional se ha descripto como relevante. Objetivo. Analizar la situación del recurso humano en las UCIP de Argentina y medir el grado de agotamiento profesional. Métodos. Estudio observacional de corte transversal, mediante la administración de encuestas por vía electrónica; se usó el cuestionario Maslach Burnout Inventory. Se invitó a participar a médicos terapistas pediátricos que se desempeñaran en el sector público o privado de la Argentina durante al menos 24 h por semana. Resultados. Fueron completadas 162 encuestas (tasa de respuesta 60%). Presentaron alto riesgo de burnout en agotamiento emocional 40 terapistas (25%), en realización personal 9 (6%) y en despersonalización 31 (19%). En forma combinada, 66 profesionales (41%) tuvieron riesgo alto de burnout en alguna de las dimensiones; resultaron factores protectores e independientes de este riesgo estar certificado en la especialidad (ORA 0,38 IC 95% 0,19-0,75) y trabajar en UCIP del sector público (ORA 0,31 IC 95% 0,15-0,65), mientras que hacer más de 36 h/semana de guardia aumentó el riesgo (ORA 1,94 IC95% 1,1-3,85). El 31 % afirmó que no planeaba continuar con actividad en cuidados intensivos y 86% no pensaban continuar con guardias en los siguientes años. La mayoría de los encuestados comunicó que modificaciones en la práctica profesional (remuneración, cargos de planta, jubilación temprana, menor carga de guardia), podrían prolongar la expectativa de continuar con actividades en UCIP. Conclusiones. Un porcentaje significativo de médicos que trabajan en las UCIP de la Argentina tienen alto riesgo de burnout y baja expectativa de continuar en la especialidad.

Introduction: there is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. Objective: to analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. Methods: an observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. Results: a total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. Conclusions: a significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Professional burnout in pediatric intensive care units in Argentina.

INTRODUCTION: There is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. OBJECTIVE: To analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. METHODS: An observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. RESULTS: A total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. CONCLUSIONS: A significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Physician's burnout in pediatric intensive care units from Argentina / Síndrome de desgaste profesional (burnout) en médicos de unidades de cuidados intensivos pediátricos en la Argentina

Introduction. There is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. Objective. To analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. Methods. An observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. Results. A total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. Conclusions. A significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Introducción. En la actualidad hay escasez de médicos en unidades de cuidados intensivos pediátricos (UCIP). La causa de este déficit es multifactorial, pero el "fenómeno de burnout" o agotamiento profesional se ha descripto como relevante. Objetivo. Analizar la situación del recurso humano en las UCIP de Argentina y medir el grado de agotamiento profesional. Métodos. Estudio observacional de corte transversal, mediante la administración de encuestas por vía electrónica; se usó el cuestionario Maslach Burnout Inventory. Se invitó a participar a médicos terapistas pediátricos que se desempeñaran en el sector público o privado de la Argentina durante al menos 24 h por semana. Resultados. Fueron completadas 162 encuestas (tasa de respuesta 60%). Presentaron alto riesgo de burnout en agotamiento emocional 40 terapistas (25%), en realización personal 9 (6%) y en despersonalización 31 (19%). En forma combinada, 66 profesionales (41%) tuvieron riesgo alto de burnout en alguna de las dimensiones; resultaron factores protectores e independientes de este riesgo estar certificado en la especialidad (ORA 0,38 IC 95% 0,19-0,75) y trabajar en UCIP del sector público (ORA 0,31 IC 95% 0,15-0,65), mientras que hacer más de 36 h/semana de guardia aumentó el riesgo (ORA 1,94 IC 95% 1,1-3,85). El 31% afirmó que no planeaba continuar con actividad en cuidados intensivos y 86% no pensaban continuar con guardias en los siguientes años. La mayoría de los encuestados comunicó que modificaciones en la práctica profesional (remuneración, cargos de planta, jubilación temprana, menor carga de guardia), podrían prolongar la expectativa de continuar con actividades en UCIP. Conclusiones. Un porcentaje significativo de médicos que trabajan en las UCIP de la Argentina tienen alto riesgo de burnout y baja expectativa de continuar en la especialidad.