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).

Evaluación del impacto de la cuarentena por la pandemia de COVID-19 en la transmisión perinatal del VIH en Buenos Aires, Argentina / Assessment of the impact of the COVID-19 pandemic lockdown on perinatal HIV transmission in Buenos Aires, Argentina

Objetivos: Describir variables epidemiológicas clave durante el año 2020 (pandemia de COVID-19) con respecto a la prevención de la transmisión perinatal (TP) del VIH en Ciudad de Buenos Aires (CABA), comparando con períodos previos.Métodos: Análisis retrospectivo de los datos agregados de TP de las principales maternidades de CABA. El año pandémico (2020) se comparó con los años no pandémicos 2018 y 2019.Resultados: Se observó una reducción del total de nacimientos en 2020 en comparación con 2019 y 2018 (11.640 vs. 14.031 y 15,978, respectivamente). La proporción de nacidos vivos en madres VIH+ (MEV) fue 0,88% en 2020, sin diferencia con 2019 y 2018 (0,94% y 0,93%), p> 0,05 para todas las comparaciones. Entre las MEV, el diagnóstico intraparto fue del 2,9% para 2020, sin diferencias con 2019 (2,25%) y 2018 (9,3%), p> 0,05 (todas las comparaciones); el 8,8% comenzó el tratamiento antirretroviral con > 28 semanas de edad gestacional en 2020 frente al 16% y el 18,05% en 2018 y 2019 (p> 0,05, todas las comparaciones). La prevalencia de la carga viral indetectable en el momento del parto fue del 67% en 2020 frente al 64% en 2018 y del 65,4% en 2019 (p> 0,05, todas las comparaciones). La transmisión perinatal fue 0% en 2020 vs. 1,33% en 2018 y 2,25% 2019 (p> 0,05, todas las comparaciones).Conclusiones: En la primera ola de la pandemia de COVID-19 no se observaron cambios en la proporción de MEV asistidas, diagnóstico intraparto de VIH, inicio tardío del TARV y TP en CABA

Background: To describe key epidemiological variables in 2020 (COVID-19 pandemic) regarding prevention of mother-to-child transmission (MTCT) in Buenos Aires city (CABA) in comparison with previous periods. Methods: Retrospective analysis of aggregated MTCT data was gathered from six principal maternity hospitals in Buenos Aires city. Pandemic year (2020) was compared to non-pandemic years 2018-19 individually considering key epidemiological variables. Results: A reduction of total births was observed in 2020 compared to 2019 and 2018 (11640 vs. 14031 and 15978, respectively). Proportion of live births in HIV-infected women (HPW) was 0.88% in 2020 without difference with 2019 and 2018 (0.94% and 0.93%), p> 0.05 for all comparisons. Among HPW, intrapartum diagnosis was 2.9% for 2020, with no difference between 2019 (2.25%) and 2018 (9.3%), p>0.05 (all comparisons); 8.8% had antiretroviral therapy (ART) started > 28 weeks of gestational age in 2020 vs. 16% and 18.05% in 2018 and 2019 (p> 0.05, all comparisons). Prevalence of undetectable viral load at delivery was 67% in 2020 vs 64% in 2018 and 65.4% in 2019 (p> 0.05, all comparisons). Perinatal transmission was 0% in 2020 vs 1.33% in 2018 and 2.25% 2019 (p> 0.05, all comparisons) Conclusions: In first wave of COVID 19 pandemic no changes in the proportion of HPW assisted, HIV intrapartum diagnosis, late ART initiation and MTCT-rate was observed in CABA

Aulas como contextos de aceptación y apoyo para integrar a los alumnos rechazados / Classrooms as contexts of acceptance and support for integrating rejected students

El GREI (Grupo interuniversitario de investigación del Rechazo Entre Iguales en contextos escolares) lleva varios años tratando de formular una respuesta global con el objetivo de favorecer la integración social y escolar del alumnado en situación de rechazo, desarrollando en las aulas un clima de convivencia, aceptación y apoyo a todos los niños y niñas. En el presente artículo se presenta la fundamentación, objetivos, características, componentes y resultados iniciales de este modelo de intervención que se caracteriza por ser multinivel, multicomponente y multiagente, y por combinar una intervención de carácter general, esto es, dirigida a todo el alumnado participante, y una intervención específica, centrada en niños y niñas objeto de rechazo por parte de sus compañeros. Participan alumnos, compañeros, profesores y padres. Los componentes esenciales son la formación y acompañamiento del profesorado y de las familias, y los programas: gestión social del aula, aprendizaje cooperativo, desarrollo socioemocional, aprendizaje de la amistad, los padres como facilitadores de las amistades de los hijos y cooperación familia-escuela. Aunque los resultados son aún preliminares, parecen apuntar con claridad hacia la mejora en los procesos relacionales del aula y, específicamente, a la prevención del rechazo entre iguales (AU)

The GREI Team (Grupo interuniversitario de investigación del Rechazo Entre Iguales en contextos escolares) has been working for several years to formulate a comprehensive response to the objective of promoting social and academic integration of rejected students, by providing a harmonious classroom atmosphere , acceptance and support for all children. This paper describes the basis, objectives, features, components, and first results of this intervention model, characterized by being multi-level, multi-component and multi-agent, and combining a general intervention addressed to all participating students, with a specific intervention focusing on peer rejected children. Participants are the students, peers, teachers, and parents. The essential components are the training and support of teachers and families, and the programs are: social management of the classroom, cooperative learning, emotional development, friendship learning, parents as facilitators of their children’s friendships, and home-school cooperation. Although results are still preliminary, they seem to point clearly to improving the classroom relational processes, and specifically, to preventing peer rejection (AU)

Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen.

INTRODUCTION: Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of antiretroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP. METHODS: Twenty pregnant women (ART-naive or preexposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour <50 copies/ml. Samples were collected between 1 and 15 months (median: 3 months) after ART interruption. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed. RESULTS: No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. Four women were re-exposed to 3TC/ZDV/NVP and achieved HIV VL <50 copies/ml. No perinatal transmission occurred in any of the 22 births. CONCLUSIONS: NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.