ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.

Children hospitalized for COVID-19 during the first winter of the pandemic in Buenos Aires, Argentina.

BACKGROUND: Although there are reports on COVID-19 in pediatrics, the characteristics of the population of each country, its health systems, and how the pandemic was addressed could give the disease distinctive features worldwide. We aimed to describe the characteristics of patients hospitalized for COVID-19 in a tertiary pediatric hospital in the City of Buenos Aires, Argentina. METHODS: We conducted a descriptive study, including all patients hospitalized for COVID-19 from 04/26/2020 to 10/31/2020 in a tertiary pediatric hospital. We described the demographic, clinical, and epidemiological characteristics of the patients. RESULTS: During the period studied, 578 patients were hospitalized with COVID-19. The median age was 4.2 years, and 83% reported close contact with a confirmed COVID-19 case. Regarding severity, 30.8% were asymptomatic, and 60.4% showed mild, 7.4% moderate, and 1.4% severe symptoms. Among symptomatic patients, fever was the most frequent symptom, followed by sore throat and cough. CONCLUSIONS: We reported 578 cases of children and adolescents hospitalized with COVID-19, of which the majority showed mild or asymptomatic disease.

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).

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).

Patients assisted at the Department of Medicine of a pediatric hospital at the beginning of the COVID-19 pandemic in Buenos Aires, Argentina. / Pacientes asistidos en el Departamento de Medicina de un hospital pediátrico en el inicio de la pandemia COVID-19 en Buenos Aires, Argentina.

INTRODUCTION: Despite the magnitude of the COVID-19 pandemic, the information about its development in pediatrics is still limited. This report describes the characteristics of patients admitted to a children's hospital due to COVID-19 during the first three months of the pandemic. METHOD: Descriptive study including all patients hospitalized due to COVID-19 between 4/1/2020 and 6/30/2020. RESULTS: A total of 191 patients were hospitalized due to COVID-19; their median age was 7.7 years; 89% had a history of close contact. Of them, 35.6 % were considered asymptomatic; 61.2 %, mild cases; and 3.2 %, moderate cases (no severe cases). None of them received a specific treatment for the disease. The most common symptoms were fever, sore throat, and cough. The median length of stay was 6 days. CONCLUSION: A total of 191 cases of children and adolescents admitted due to COVID-19 are reported. Most were asymptomatic or presented with a mild disease.

Introducción. A pesar de la magnitud de la pandemia por COVID-19, la información sobre su desarrollo en pediatría es aún limitada. Se describen las características de pacientes hospitalizados por COVID-19 en un hospital pediátrico durante los primeros tres meses de la pandemia. Método. Estudio descriptivo, que incluyó a todos los pacientes hospitalizados por COVID-19, desde el 1/4/2020 al 30/6/2020. Resultados. Se hospitalizaron 191 pacientes por COVID-19; la edad mediana fue 7,7 años; el 89 % presentaban antecedente de contacto. El 35,6 % se consideraron asintomáticos; el 61,2 %, leves, y el 3,2 %, moderados (no se observaron pacientes graves). Ninguno recibió tratamiento específico para la enfermedad. Los síntomas más frecuentes fueron fiebre, odinofagia y tos. La duración de la hospitalización tuvo una mediana de 6 días. Conclusión. Se reportaron 191 casos de niños y adolescentes hospitalizados por COVID-19. La mayoría fueron asintomáticos o presentaron enfermedad leve.

Miositis aguda asociada a infección por virus influenza. Serie de casos en un hospital pediátrico / Acute myositis associated with influenza infection. Case series in a pediatric hospital

La miositis aguda benigna asociada a influenza es una complicación esporádica. En Argentina, en el año 2022, hubo un aumento temprano de la circulación de influenza y del número total de las notificaciones, con la aparición de miositis secundarias. Serie clínica retrospectiva de nueve pacientes pediátricos que consultaron por dolor e impotencia funcional de extremidades inferiores, y enzimas musculares elevadas, en el hospital Pedro de Elizalde de la Ciudad Autónoma de Buenos Aires, entre agosto y octubre del 2022. En todos se detectó infección por virus influenza y se recuperaron sin secuelas. La miositis aguda benigna es una entidad infrecuente en la infancia, cuyo diagnóstico es predominantemente clínico y de recuperación ad integrum. Debe ser sospechada en pacientes con clínica compatible en contexto de alta circulación viral. La vigilancia epidemiológica aporta herramientas para identificar los virus circulantes y sus posibles complicaciones.

Benign acute myositis associated with influenza is a sporadic complication. In Argentina, in 2022, there was an early increase in influenza circulation and the total number of notifications, with the appearance of secondary myositis. Retrospective clinical series of nine pediatric patients who consulted for pain and functional impotence of the lower extremities, and elevated muscle enzymes, at the Pedro de Elizalde hospital in the Autonomous City of Buenos Aires, between August and October 2022. In all of them, infection by influenza virus and recovered without sequelae. Benign acute myositis is a rare entity in childhood, whose diagnosis is predominantly clinical and recovery ad integrum. It should be suspected in patients with compatible symptoms in a context of high viral circulation. Epidemiological surveillance provides tools to identify circulating viruses and their possible complications.

Pacientes asistidos en el Departamento de Medicina de un hospital pediátrico en el inicio de la pandemia COVID-19 en Buenos Aires, Argentina / Patients assisted at the Department of Medicine of a pediatric hospital at the beginning of the COVID-19 pandemic in Buenos Aires, Argentina

Introducción. A pesar de la magnitud de la pandemia por COVID-19, la información sobre su desarrollo en pediatría es aún limitada. Se describen las características de pacientes hospitalizados por COVID-19 en un hospital pediátrico durante los primeros tres meses de la pandemia.Método. Estudio descriptivo, que incluyó a todos los pacientes hospitalizados por COVID-19, desde el 1/4/2020 al 30/6/2020.Resultados. Se hospitalizaron 191 pacientes por COVID-19; la edad mediana fue 7,7 años; el 89 % presentaban antecedente de contacto. El 35,6 % se consideraron asintomáticos; el 61,2 %, leves, y el 3,2 %, moderados (no se observaron pacientes graves). Ninguno recibió tratamiento específico para la enfermedad. Los síntomas más frecuentes fueron fiebre, odinofagia y tos. La duración de la hospitalización tuvo una mediana de 6 días.Conclusión. Se reportaron 191 casos de niños y adolescentes hospitalizados por COVID-19. La mayoría fueron asintomáticos o presentaron enfermedad leve.

Introduction. Despite the magnitude of the COVID-19 pandemic, the information about its development in pediatrics is still limited. This report describes the characteristics of patients admitted to a children's hospital due to COVID-19 during the first three months of the pandemic.Method. Descriptive study including all patients hospitalized due to COVID-19 between 4/1/2020 and 6/30/2020.Results. A total of 191 patients were hospitalized due to COVID-19; their median age was 7.7 years; 89 % had a history of close contact. Of them, 35.6 % were considered asymptomatic; 61.2 %, mild cases; and 3.2 %, moderate cases (no severe cases). None of them received a specific treatment for the disease. The most common symptoms were fever, sore throat, and cough. The median length of stay was 6 days.Conclusion. A total of 191 cases of children and adolescents admitted due to COVID-19 are reported. Most were asymptomatic or presented with a mild disease

[Gradenigo's syndrome: a case-report]. / Síndrome de Gradenigo: comunicación de un caso.

Acute otitis media is the most common bacterial infection in children. Despite efficient antibiotic therapy, there are still reports of both intratemporal and intracranial complications with potential risk of high morbidity and mortality. Mastoiditis, apical petrositis and labyrinthitis are caused by the extension of purulent middle ear infection into nearby structures. Giuseppe Gradenigo first described the clinical triad of acute otitis media, unilateral pain in the region innervated by the 1 masculine and 2 masculine branches of the trigeminal nerve and ipsilateral abducens nerve paralysis. This is a serious but rare complication of middle ear infection that should be suspected in every patient with unilateral headache and abducens nerve palsy. We report a case of Gradenigo's syndrome in a 6-year-old boy.

[Nephromegaly: as unusual presentation of acute lymphoblastic leukemia in an infant]. / Nefromegalia: forma de presentación infrecuente de leucemia linfoblástica aguda en un lactante.

Nephromegaly in infancy may be due to several causes, being the most relevant: renal polycystic autosomic recessive disease, venous renal thrombosis, deposit diseases, kidney tumors, nephrotic congenital syndrome and neoplastic infiltration. Although renal infiltration is relatively frequent in acute lymphoblastic leukemia, nephromegaly is an unusual form of presentation in this pathology. The case of a four-year-old patient, who presents bilateral nephromegaly and pancytopenia, is presented. Acute Lymphoblastic Leukemia is diagnosed, initiating the corresponding chemotherapic treatment.

Síndrome de Gradenigo: comunicación de un caso / Gradenigo´s syndrome: a case-report

La otitis media aguda (OMA) es la infección bacteriana másfrecuente en pediatría. A pesar de la existencia de tratamiento antibiótico adecuado aún existen casos de complicaciones intratemporales o intracraneales con riesgo potencial de morbimortalidad elevada. Mastoiditis, petrositis y laberintitis se producen como consecuencia de la extensión del proceso supurado desde el oído medio a las estructuras adyacentes. GiuseppeGradenigo fue quien describió la tríada de otitis media aguda, dolor unilateral en las áreas inervadas por la 1a y 2a ramas del nervio trigémino y parálisis del 6º par craneal. Esta es una grave, aunque rara, complicación de la OMA, que debe ser sospechada en todo paciente con cefalea unilateral y parálisis del 6º par craneal. Presentamos el caso de un niño de 6años con síndrome de Gradenigo.(AU)

Síndrome de Gradenigo: comunicación de un caso / Gradenigo´s syndrome: a case-report

La otitis media aguda (OMA) es la infección bacteriana másfrecuente en pediatría. A pesar de la existencia de tratamiento antibiótico adecuado aún existen casos de complicaciones intratemporales o intracraneales con riesgo potencial de morbimortalidad elevada. Mastoiditis, petrositis y laberintitis se producen como consecuencia de la extensión del proceso supurado desde el oído medio a las estructuras adyacentes. GiuseppeGradenigo fue quien describió la tríada de otitis media aguda, dolor unilateral en las áreas inervadas por la 1a y 2a ramas del nervio trigémino y parálisis del 6º par craneal. Esta es una grave, aunque rara, complicación de la OMA, que debe ser sospechada en todo paciente con cefalea unilateral y parálisis del 6º par craneal. Presentamos el caso de un niño de 6años con síndrome de Gradenigo.

Nefromegalia: forma de presentación infrecuente de leucemia linfoblástica en un paciente / Nephromegaly, as unusual presentation of acute lymphoblastic leukemia in a infant

La nefromegalia en un lactante puede responder a múltiples causas; las más destacadas son: enfermedad renal poliquísticaautosómica recesiva, trombosis venosa renal, tesaurismosis, tumores renales, síndrome nefrótico congénito e infiltracióntumoral. La infiltración renal es relativamente frecuente en laleucemia linfoblástica aguda, pero la nefromegalia es una forma de presentación inusual en esta patología.Presentamos el caso de una paciente de 4 meses de edad, quienpresenta nefromegalia bilateral y pancitopenia. Se le realizadiagnóstico de leucemia linfoblástica aguda e inicia el tratamiento quimioterápico correspondiente (AU)

Nephromegaly in infancy may be due to several causes, being the most relevant: renal polycystic autosomic recessive disease, venous renal thrombosis, deposit diseases, kidney tumors, nephrotic congenital syndrome and neoplasic infiltration. Although renal infiltration is relatively frecuent in acute lymphoblastic leukemia, nephromegaly is an unusual form of presentation in this pathology. The case of a four-year-old patient, who presents bilateral nephromegaly and pancytopenia, is presented. Acute Lymphoblastic Leukemia is diagnosed, initiating the corresponding chemotherapic treatment.(AU)

Nefromegalia: forma de presentación infrecuente de leucemia linfoblástica en un paciente / Nephromegaly, as unusual presentation of acute lymphoblastic leukemia in a infant

La nefromegalia en un lactante puede responder a múltiples causas; las más destacadas son: enfermedad renal poliquísticaautosómica recesiva, trombosis venosa renal, tesaurismosis, tumores renales, síndrome nefrótico congénito e infiltracióntumoral. La infiltración renal es relativamente frecuente en laleucemia linfoblástica aguda, pero la nefromegalia es una forma de presentación inusual en esta patología.Presentamos el caso de una paciente de 4 meses de edad, quienpresenta nefromegalia bilateral y pancitopenia. Se le realizadiagnóstico de leucemia linfoblástica aguda e inicia el tratamiento quimioterápico correspondiente

Nephromegaly in infancy may be due to several causes, being the most relevant: renal polycystic autosomic recessive disease, venous renal thrombosis, deposit diseases, kidney tumors, nephrotic congenital syndrome and neoplasic infiltration. Although renal infiltration is relatively frecuent in acute lymphoblastic leukemia, nephromegaly is an unusual form of presentation in this pathology. The case of a four-year-old patient, who presents bilateral nephromegaly and pancytopenia, is presented. Acute Lymphoblastic Leukemia is diagnosed, initiating the corresponding chemotherapic treatment.

Información sobre salud en Internet: su empleo por pediatras y padres de pacientes / Pediatricians and patients parents´use of the Internet to obtain health information

Introducción. Internet puede generar cambios enrelación médico-paciente. Describimos indicadores sobre la conducta de pediatras y pacientes con respectoal uso de Internet. Población, material y métodos. Encuestamos 1.432 pediatras y 501 padres de pacientes. Se recogió información sobre el uso de Internet para búsqueda de información y comunicación médico-paciente.Resultados. Respondieron 291 pediatras; 97% utilizóInternet para búsqueda de información sobresalud y 85% aceptó que sus pacientes lo hicieran.Todos los padres respondieron las encuestas; 82,7%utilizó Internet, 46% buscó información sobre salud,15% lo comentó con su pediatra y 5% recibió orientación para la búsqueda.Conclusiones. Muchos pediatras utilizan Internet en su profesión y aceptan que los pacientes busquen información sobre salud. La mitad de los padres buscó información sobre salud en la web, pero sólo15% lo comentó con su pediatra. Muy pocos padres recibieron orientación de su pediatra para buscar información en Internet.(AU)

Introduction. Internet can generate changes in the patient-physician relationship. We describe indicators of pediatricians and patients conduct regarding the use of Internet. Population, material and methods. We surveyed 1432 pediatricians and 501 patients parentsã. Information regarding Internet use for health information search and patient-physician communication was retrieved. Results. A total of 291 pediatricians responded; 97% used the Internet for health information search and 85% accepted that their patients used it for the same purpose. All parents answered the survey; 82.7% used the Internet, 46% searched for health information, 15% shared their findings with their pediatrician and 5% received orientation for their search. Conclusion. Many pediatricians use the Internet in their work and accept that their patients search for health information on the web. Half of the parents searched for health-related information on the web, although only 15% shared the findings with their pediatrician. Very few parents received some kind of orientation for health information searching on the Internet.(AU)

Información sobre salud en Internet: su empleo por pediatras y padres de pacientes / Pediatricians and patients parents´use of the Internet to obtain health information

Introducción. Internet puede generar cambios enrelación médico-paciente. Describimos indicadores sobre la conducta de pediatras y pacientes con respectoal uso de Internet. Población, material y métodos. Encuestamos 1.432 pediatras y 501 padres de pacientes. Se recogió información sobre el uso de Internet para búsqueda de información y comunicación médico-paciente.Resultados. Respondieron 291 pediatras; 97% utilizóInternet para búsqueda de información sobresalud y 85% aceptó que sus pacientes lo hicieran.Todos los padres respondieron las encuestas; 82,7%utilizó Internet, 46% buscó información sobre salud,15% lo comentó con su pediatra y 5% recibió orientación para la búsqueda.Conclusiones. Muchos pediatras utilizan Internet en su profesión y aceptan que los pacientes busquen información sobre salud. La mitad de los padres buscó información sobre salud en la web, pero sólo15% lo comentó con su pediatra. Muy pocos padres recibieron orientación de su pediatra para buscar información en Internet.

Introduction. Internet can generate changes in the patient-physician relationship. We describe indicators of pediatricians and patients conduct regarding the use of Internet. Population, material and methods. We surveyed 1432 pediatricians and 501 patients parents’. Information regarding Internet use for health information search and patient-physician communication was retrieved. Results. A total of 291 pediatricians responded; 97% used the Internet for health information search and 85% accepted that their patients used it for the same purpose. All parents answered the survey; 82.7% used the Internet, 46% searched for health information, 15% shared their findings with their pediatrician and 5% received orientation for their search. Conclusion. Many pediatricians use the Internet in their work and accept that their patients search for health information on the web. Half of the parents searched for health-related information on the web, although only 15% shared the findings with their pediatrician. Very few parents received some kind of orientation for health information searching on the Internet.