Evolutionary dynamics of respiratory syncytial virus in Buenos Aires: Viral diversity, migration, and subgroup replacement.

Globally, the human respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections (LRTIs) in children. The scarcity of complete genome data limits our understanding of RSV spatiotemporal distribution, evolution, and viral variant emergence. Nasopharyngeal samples collected from hospitalized pediatric patients from Buenos Aires tested positive for RSV LRTI during four consecutive outbreaks (2014-2017) were randomly subsampled for RSV complete genome sequencing. Phylodynamic studies and viral population characterization of genomic variability, diversity, and migration of viruses to and from Argentina during the study period were performed. Our sequencing effort resulted in one of the largest collections of RSV genomes from a given location (141 RSV-A and 135 RSV-B) published so far. RSV-B was dominant during the 2014-2016 outbreaks (60 per cent of cases) but was abruptly replaced by RSV-A in 2017, with RSV-A accounting for 90 per cent of sequenced samples. A significant decrease in RSV genomic diversity-represented by both a reduction in genetic lineages detected and the predominance of viral variants defined by signature amino acids-was observed in Buenos Aires in 2016, the year prior to the RSV subgroup predominance replacement. Multiple introductions to Buenos Aires were detected, some with persistent detection over seasons, and also, RSV was observed to migrate from Buenos Aires to other countries. Our results suggest that the decrease in viral diversity may have allowed the dramatic predominance switch from RSV-B to RSV-A in 2017. The immune pressure generated against circulating viruses with limited diversity during a given outbreak may have created a fertile ground for an antigenically divergent RSV variant to be introduced and successfully spread in the subsequent outbreak. Overall, our RSV genomic analysis of intra- and inter-outbreak diversity provides an opportunity to better understand the epochal evolutionary dynamics of RSV.

Assessing the hidden diversity underlying consensus sequences of SARS-CoV-2 using VICOS, a novel bioinformatic pipeline for identification of mixed viral populations.

INTRODUCTION: Coinfection with two SARS-CoV-2 viruses is still a very understudied phenomenon. Although next generation sequencing methods are very sensitive to detect heterogeneous viral populations in a sample, there is no standardized method for their characterization, so their clinical and epidemiological importance is unknown. MATERIAL AND METHODS: We developed VICOS (Viral COinfection Surveillance), a new bioinformatic algorithm for variant calling, filtering and statistical analysis to identify samples suspected of being mixed SARS-CoV-2 populations from a large dataset in the framework of a community genomic surveillance. VICOS was used to detect SARS-CoV-2 coinfections in a dataset of 1,097 complete genomes collected between March 2020 and August 2021 in Argentina. RESULTS: We detected 23 cases (2%) of SARS-CoV-2 coinfections. Detailed study of VICOS's results together with additional phylogenetic analysis revealed 3 cases of coinfections by two viruses of the same lineage, 2 cases by viruses of different genetic lineages, 13 were compatible with both coinfection and intra-host evolution, and 5 cases were likely a product of laboratory contamination. DISCUSSION: Intra-sample viral diversity provides important information to understand the transmission dynamics of SARS-CoV-2. Advanced bioinformatics tools, such as VICOS, are a necessary resource to help unveil the hidden diversity of SARS-CoV-2.

Dengue más allá del trópico: estudio de series temporales 2015-2016 versus 2019-2020 en un hospital pediátrico de la Ciudad de Buenos Aires / Dengue beyond the tropics: a time-series study comprising 2015-2016 versus 2019-2020 at a children's hospital in the City of Buenos Aires

Introducción. El dengue es un problema de salud pública a nivel mundial. Confinado en sus orígenes a las zonas tropicales y subtropicales, en la actualidad se presenta en otras regiones como Argentina. Desde el año 2008 se presenta con brotes epidémicos en la Ciudad Autónoma de Buenos Aires, con escasos reportes en niños. Objetivo. Analizar y comparar las características clínicas, epidemiológicas, de laboratorio y evolutivas de los dos últimos brotes de dengue fuera del área endémica. Población y métodos. Estudio de series temporales. Se incluyeron pacientes menores de 18 años con dengue probable o confirmado, evaluados en un hospital pediátrico de la Ciudad de Buenos Aires durante los períodos 2015-2016 y 2019-2020. Resultados. Se incluyeron 239 pacientes, 29 (12 %) con antecedente de viaje. La mediana de edad fue de 132 meses (rango intercuartílico: 102-156). Todos tuvieron fiebre. Otros síntomas fueron: cefalea en 170 (71 %), mialgias en 129 (54 %) y exantema en 122 (51 %). Cuarenta pacientes (17 %) tenían comorbilidades. Presentaron signos de alarma 79 pacientes (33 %) y 14 (6 %) tenían dengue grave. Requirieron internación 115 pacientes (45 %) y ninguno falleció. El serotipo DENV-1 fue el más frecuente. El antecedente de viaje y la necesidad de internación predominaron en el primer período; el dengue grave y la infección previa, en el segundo. Conclusiones. Ningún paciente falleció de dengue en los períodos estudiados. Se observaron diferencias estadísticamente significativas en la frecuencia de internación; el antecedente de viaje fue más frecuente en el período 2015-2016 y el dengue grave, en el 2019-2020.

Introduction. Dengue is a public health problem worldwide. It was originally confined to tropical and subtropical areas, but it is now present in other regions, such as Argentina. Epidemic outbreaks have been observed in the City of Buenos Aires since 2008, with few reports in children. Objective. To analyze and compare the clinical, epidemiological, laboratory, and evolutionary characteristics of the latest 2 dengue outbreaks outside the endemic area. Population and methods. Time-series study. Patients under 18 years of age with probable or confirmed dengue and evaluated in a children's hospital of the City of Buenos Aires during the periods 2015-2016 and 2019-2020 were included. Results. A total of 239 patients were included; 29 (12%) had a history of travel. Their median age was 132 months (interquartile range: 102156). All had a fever. Other symptoms included headache in 170 (71%), myalgia in 129 (54%), and rash in 122 (51%). Forty patients (17%) had comorbidities. Warning signs were observed in 79 patients (33%); 14 (6%) developed severe dengue; 115 (45%) were hospitalized; none died. DENV-1 was the most common serotype. A history of travel and hospitalization prevailed in the first period; severe dengue and prior infection, in the second period. Conclusions. No patient died due to dengue in either study period. Statistically significant differences were observed in the frequency of hospitalization; a history of travel was more common in the 2015-2016 period and severe dengue, in the 2019-2020 period.

Dengue beyond the tropics: a time-series study comprising 2015-2016 versus 2019-2020 at a children's hospital in the City of Buenos Aires. / Dengue más allá del trópico: estudio de series temporales 2015-2016 versus 2019-2020 en un hospital pediátrico de la Ciudad de Buenos Aires.

INTRODUCTION: Dengue is a public health problem worldwide. It was originally confined to tropical and subtropical areas, but it is now present in other regions, such as Argentina. Epidemic outbreaks have been observed in the City of Buenos Aires since 2008, with few reports in children. OBJECTIVE: To analyze and compare the clinical, epidemiological, laboratory, and evolutionary characteristics of the latest 2 dengue outbreaks outside the endemic area. POPULATION AND METHODS: Time-series study. Patients under 18 years of age with probable or confirmed dengue and evaluated in a children's hospital of the City of Buenos Aires during the periods 2015-2016 and 2019-2020 were included. RESULTS: A total of 239 patients were included; 29 (12%) had a history of travel. Their median age was 132 months (interquartile range: 102- 156). All had a fever. Other symptoms included headache in 170 (71%), myalgia in 129 (54%), and rash in 122 (51%). Forty patients (17%) had comorbidities. Warning signs were observed in 79 patients (33%); 14 (6%) developed severe dengue; 115 (45%) were hospitalized; none died. DENV-1 was the most common serotype. A history of travel and hospitalization prevailed in the first period; severe dengue and prior infection, in the second period. CONCLUSIONS: No patient died due to dengue in either study period. Statistically significant differences were observed in the frequency of hospitalization; a history of travel was more common in the 2015-2016 period and severe dengue, in the 2019-2020 period.

Introducción. El dengue es un problema de salud pública a nivel mundial. Confinado en sus orígenes a las zonas tropicales y subtropicales, en la actualidad se presenta en otras regiones como Argentina. Desde el año 2008 se presenta con brotes epidémicos en la Ciudad Autónoma de Buenos Aires, con escasos reportes en niños. OBJETIVO: Analizar y comparar las características clínicas, epidemiológicas, de laboratorio y evolutivas de los dos últimos brotes de dengue fuera del área endémica. Población y métodos. Estudio de series temporales. Se incluyeron pacientes menores de 18 años con dengue probable o confirmado, evaluados en un hospital pediátrico de la Ciudad de Buenos Aires durante los períodos 2015-2016 y 2019-2020. RESULTADOS: Se incluyeron 239 pacientes, 29 (12 %) con antecedente de viaje. La mediana de edad fue de 132 meses (rango intercuartílico: 102-156). Todos tuvieron fiebre. Otros síntomas fueron: cefalea en 170 (71 %), mialgias en 129 (54 %) y exantema en 122 (51 %). Cuarenta pacientes (17 %) tenían comorbilidades. Presentaron signos de alarma 79 pacientes (33 %) y 14 (6 %) tenían dengue grave. Requirieron internación 115 pacientes (45 %) y ninguno falleció. El serotipo DENV-1 fue el más frecuente. El antecedente de viaje y la necesidad de internación predominaron en el primer período; el dengue grave y la infección previa, en el segundo. CONCLUSIONES: Ningún paciente falleció de dengue en los períodos estudiados. Se observaron diferencias estadísticamente significativas en la frecuencia de internación; el antecedente de viaje fue más frecuente en el período 2015-2016 y el dengue grave, en el 2019-2020.

Agreement between diagnostic methods for SARS-CoV-2 infection in children seen at the Emergency Department of a children's hospital. / Concordancia entre métodos diagnósticos de infección por SARS-CoV-2 en niños asistidos en el departamento de urgencias de un hospital pediátrico.

INTRODUCTION: Rapid antigen tests (RAgTs) for SARS-CoV-2 are considered adequate for diagnosis at the point of care. Our objective was to establish the agreement between reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RAgTs in the pediatric population. POPULATION AND METHODS: All patients aged 1 month to 17 years and 11 months seen at the Emergency Fever Unit of a children's hospital between 6-11-2021 and 10-3-2021 were recruited. The Panbio COVID-19 Ag® test (Abbott Diagnostic) was compared to the reference method RT-qPCR (as per the protocol suggested by the United States Centers for Disease Control and Prevention). RESULTS: A total of 6491 patients were included. The prevalence of COVID-19 was 2.8%. Symptoms were observed in 92.1%. Sensitivity, specificity, and the kappa index of agreement for the RAgT were 71.0%, 99.9%, and 0.813, respectively. The kappa index and the RAgT sensitivity were significantly higher in the group aged 13-17 years (0.89 and 82.4%, respectively) compared to the groups aged 0-5 and 6-12 years. This may be due to the lower viral load observed in patients younger than 12 years. CONCLUSIONS: Although RAgTs shorten the time to result and improve the isolation strategy for COVID-19 patients, their sensitivity in children younger than 12 years or asymptomatic children is not within the recommended ranges, especially during periods of low disease prevalence.

Introducción. Los inmunoensayos de detección rápida de antígenos (TRA) del SARS-CoV-2, son considerados adecuados para el diagnóstico en el punto de atención. El objetivo fue conocer la concordancia entre la reacción en cadena de la polimerasa en tiempo real con transcriptasa inversa (RT-qPCR, por su sigla en inglés) y los TRA en población pediátrica. Población y métodos. Se reclutaron todos los pacientes entre 1 mes y 17 años 11 meses de edad atendidos en la Unidad Febril de Urgencia de un hospital pediátrico entre el 11 de junio y el 3 de octubre de 2021. Se utilizó el TRA Panbio COVID-19 Ag® (Abbott Diagnostic) y, como método de referencia, la RT-qPCR (según el protocolo de los Centros para el Control y la Prevención de Enfermedades). Resultados. Se incluyeron 6491 pacientes. La prevalencia de COVID-19 fue del 2,8 %. El 92,1 % de los sujetos presentaron síntomas. La sensibilidad, la especificidad y el índice kappa de concordancia para el TRA fueron del 71,0 %, 99,9 % y 0,813, respectivamente. El índice kappa y la sensibilidad del TRA fueron significativamente mayores en el grupo de 13 a 17 años (0,89 y 82,4 %, respectivamente) cuando se los comparó con los grupos de 0 a 5 y de 6 a 12 años. Esto podría deberse a la menor carga viral observada en los pacientes menores de 12 años. Conclusión. Si bien los TRA permiten acortar el tiempo de obtención de los resultados y mejorar la estrategia de aislamiento de pacientes con COVID-19, la sensibilidad en niños menores de 12 años o asintomáticos no se encontraría dentro de los rangos recomendados, sobre todo en períodos de baja prevalencia de la enfermedad.

Concordancia entre métodos diagnósticos de infección por SARS-CoV-2 en niños asistidos en el departamento de urgencias de un hospital pediátrico / Agreement between diagnostic methods for SARS-CoV-2 infection in children seen at the Emergency Department of a children's hospital

Introducción. Los inmunoensayos de detección rápida de antígenos (TRA) del SARS-CoV-2, son considerados adecuados para el diagnóstico en el punto de atención. El objetivo fue conocer la concordancia entre la reacción en cadena de la polimerasa en tiempo real con transcriptasa inversa (RT-qPCR, por su sigla en inglés) y los TRA en población pediátrica. Población y métodos. Se reclutaron todos los pacientes entre 1 mes y 17 años 11 meses de edad atendidos en la Unidad Febril de Urgencia de un hospital pediátrico entre el 11 de junio y el 3 de octubre de 2021. Se utilizó el TRA Panbio COVID-19 Ag® (Abbott Diagnostic) y, comométodo de referencia, la RT-qPCR (según el protocolo de los Centros para el Control y la Prevención de Enfermedades). Resultados. Se incluyeron 6491 pacientes. La prevalencia de COVID-19 fue del 2,8 %. El92,1 % de los sujetos presentaron síntomas. La sensibilidad, la especificidad y el índice kappa de concordancia para el TRA fueron del 71,0 %, 99,9 % y 0,813, respectivamente. El índice kappa yla sensibilidad del TRA fueron significativamentemayores en el grupo de 13 a 17 años (0,89 y 82,4 %,respectivamente) cuando se los comparó con los grupos de 0 a 5 y de 6 a 12 años. Esto podría deberse a la menor carga viral observada en los pacientes menores de 12 años. Conclusión. Si bien los TRA permiten acortar el tiempo de obtención de los resultados y mejorar la estrategia de aislamiento de pacientes con COVID-19, la sensibilidad en niños menores de 12 años o asintomáticos no se encontraría dentro de los rangos recomendados, sobre todo enperíodos de baja prevalencia de la enfermedad.

Introduction. Rapid antigen tests (RAgTs) for SARS-CoV-2 are considered adequate for diagnosis at the point of care. Our objective was to establish the agreement between reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RAgTs in the pediatric population. Population and methods. All patients aged 1 month to 17 years and 11 months seen at the Emergency Fever Unit of a children's hospital between 6-11-2021 and 10-3-2021 were recruited. The Panbio COVID-19 Ag® test (Abbott Diagnostic) was compared to the reference method RT-qPCR (as per the protocol suggested by the United States Centers for Disease Control and Prevention). Results. A total of 6491 patients were included. The prevalence of COVID-19 was 2.8%. Symptoms were observed in 92.1%. Sensitivity, specificity, and the kappa index of agreement for the RAgT were 71.0%, 99.9%, and 0.813, respectively. The kappa index and the RAgT sensitivity were significantly higher in the group aged 13­17 years (0.89 and 82.4%, respectively) compared to the groups aged 0­5 and 6­12 years. This may be due to the lower viral load observed in patients younger than 12 years. Conclusion. Although RAgTs shorten the time to result and improve the isolation strategy for COVID-19 patients, their sensitivity in children younger than 12 years or asymptomatic children is not within the recommended ranges, especially during periods of low disease prevalence.

Vigilancia de virus sincicial respiratorio e influenza en niños escolarizados asistidos en un hospital pediátrico durante 2 meses del segundo semestre de 2021 / Respiratory syncytial virus and influenza surveillance in schoolchildren seen at a children's hospital over 2 months of the second semester of 2021

Introducción. Durante la pandemia de COVID-19, disminuyeron las notificaciones de infecciones respiratorias. El objetivo fue estimar la prevalencia de virus sincicial respiratorio (VSR) e influenza en niños escolarizados asistidos en un hospital pediátrico durante el retorno a la presencialidad. Métodos. Estudio transversal de casos sospechosos de COVID-19, de 3-18 años, con prueba negativa para SARSCoV-2, entre agosto y octubre de 2021. Se estratificó por nivel educativo. Se utilizó PCR para detectar VSR e influenza. Resultados. Se incluyeron 619 niños: 234 del nivel inicial, 224 del primario y 161 del secundario; 25,5 % (158) fueron positivos para VSR (36,3 % del nivel inicial versus 21 % del primario y 16 % del secundario); en adolescentes se asoció la infección al contacto escolar con caso sintomático (OR 2,5; IC95%: 1-6,80; p = 0,04). No se aisló virus influenza. Conclusión. VSR se aisló en un cuarto de la población estudiada, con mayor frecuencia en el nivel inicial; en adolescentes, se asoció con contacto escolar sintomático. No se detectaron casos de influenza

Introduction. Reporting of respiratory infections reduced during the COVID-19 pandemic. The objective was to estimate the prevalence of respiratory syncytial virus (RSV) and influenza in schoolchildren seen at a children's hospital during the return to school. Methods. Cross-sectional study of patients aged 3­18 years suspected of COVID-19 with a negative test for SARS-CoV-2 between August and October 2021. Participants were stratified by level of education. PCR was used to detect RSV and influenza. Results. A total of 619 children were included: 234 in preschool, 224 in primary and 161 in secondary school; 25.5% (158) tested positive for RS (36.3% in the pre-school level versus 21% in primary and 16% in secondary school). Infection among adolescents was associated with school contact with symptomatic cases (OR 2.5; 95%CI 1­6.80; p = 0.04). No case of influenza was detected. Conclusion. RSV was isolated in one fourth of the study population, with a higher frequency in pre-school; among adolescents, it was associated with school contact with symptomatic cases. No case of influenza was detected.

Respiratory syncytial virus and influenza surveillance in schoolchildren seen at a children's hospital over 2 months of the second semester of 2021. / Vigilancia de virus sincicial respiratorio e influenza en niños escolarizados asistidos en un hospital pediátrico durante 2 meses del segundo semestre de 2021.

INTRODUCTION: Reporting of respiratory infections reduced during the COVID-19 pandemic. The objective was to estimate the prevalence of respiratory syncytial virus(RSV) and influenza in schoolchildren seen at a children's hospital during the return to school. METHODS: Cross-sectional study of patients aged 3-18 years suspected of COVID-19 with a negative test for SARS-CoV-2 between August and October 2021. Participants were stratified by level of education. PCR was used to detect RSV and influenza. RESULTS: A total of 619 children were included: 234 in pre-school, 224 in primary and 161 in secondary school; 25.5% (158) tested positive for RSV (36.3% in the pre-school level versus 21% in primary and 16% in secondary school). Infection among adolescents was associated with school contact with symptomatic cases (OR 2.5; 95%CI 1-6.80; p = 0.04). No case of influenza was detected. CONCLUSIONS: RSV was isolated in one fourth of the study population, with a higher frequency in pre-school; among adolescents, it was associated with school contact with symptomatic cases. No case of influenza was detected.

Introducción. Durante la pandemia de COVID-19, disminuyeron las notificaciones de infecciones respiratorias. El objetivo fue estimar la prevalencia de virus sincicial respiratorio (VSR) e influenza en niños escolarizados asistidos en un hospital pediátrico durante el retorno a la presencialidad. Métodos. Estudio transversal de casos sospechosos de COVID-19, de 3-18 años, con prueba negativa para SARS-CoV-2, entre agosto y octubre de 2021. Se estratificó por nivel educativo. Se utilizó PCR para detectar VSR e influenza. Resultados. Se incluyeron 619 niños: 234 del nivel inicial, 224 del primario y 161 del secundario; 25,5 % (158) fueron positivos para VSR (36,3 % del nivel inicial versus 21 % del primario y 16 % del secundario); en adolescentes se asoció la infección al contacto escolar con caso sintomático (OR 2,5; IC95%: 1-6,80; p = 0,04). No se aisló virus influenza. Conclusión. VSR se aisló en un cuarto de la población estudiada, con mayor frecuencia en el nivel inicial; en adolescentes, se asoció con contacto escolar sintomático. No se detectaron casos de influenza.

Impacto del COVID-19 en la circulación de virus respiratorios en un hospital pediátrico: una ausencia esperada / Impact of COVID-19 on the circulation of respiratory viruses in a children's hospital: an expected absence

Introducción. Los virus respiratorios son la principal causa de infección respiratoria aguda baja (IRAB) en la población pediátrica. En marzo de 2020, la Organización Mundial de la Salud declaró el estado de pandemia de la enfermedad por el nuevo coronavirus 2019 (COVID-19) con un impacto global elevado. El objetivo de este estudio fue describir el impacto de la pandemia de COVID-19 en las internaciones por IRAB en el Hospital de Niños Ricardo Gutiérrez (HNRG) y la circulación viral. Métodos. Estudio observacional, retrospectivo y descriptivo de pacientes internados por IRAB, comparando los años 2019 y 2020. Resultados. En 2020, la tasa de hospitalización por IRAB se redujo un 73 % en el HNRG (575,1/10 000 en 2019 y 155,3/10 000 en 2020). En 2019 se internaron 517 pacientes con IRAB; en 174 se identificaron los virus: sincicial respiratorio (71,2 %), adenovirus (AV) (10,3%), parainfluenza (PIF) (9,7 %) e influenza (FLU) (8,6 %). En 2020, se hospitalizaron 94 pacientes con IRAB. Hasta la semana epidemiológica (SE) 13 se registraron casos de IRAB por PIF y AV; en la SE 29 un caso de bronquiolitis por AV y rinovirus (RV), seguido de casos aislados de RV; no hubo IRAB por VSR ni por FLU. Se registraron 9 casos de IRAB por COVID-19: 2 bronquiolitis moderadas y 7 neumonías focales; con un adolescente fallecido por neumonía por COVID-19 con comorbilidades. En 2020, los casos presentaron mayor edad, más comorbilidades e internaciones previas en comparación con el 2019. La neumonía focal fue la presentación clínica predominante. Conclusión. En 2020, la tasa de hospitalización por IRAB se redujo significativamente en comparación con el año anterior, con ausencia de circulación de virus respiratorios estacionales en la población asistida en nuestro centro.

Introduction. Respiratory viruses are the main cause of acute lower respiratory tract infection (ALRTI) in the pediatric population. In March 2020, the World Health Organization declared that the new coronavirus disease 2019 (COVID-19) had reached the pandemic status. Our objective was to describe the impact of COVID-19 pandemic on hospitalizations due to ALRTI at Hospital de Niños Ricardo Gutiérrez (HNRG) and virus circulation. Methods. Observational, retrospective, and descriptive study of patients hospitalized due to ALRTI comparing 2019 and 2020. Results. In 2020, the rate of hospitalization due to ALRTI decreased by 73%. In 2019, 517 patients with ALRTI were hospitalized; the following viruses were identified in 174: respiratory syncytial virus (RSV) (71.2%), adenovirus (AV) (10.3%), parainfluenza virus (PIV) (9.7%), and influenza virus (FLU) (8.6%). In 2020, 94 patients with ALRTI were hospitalized. Until epidemiological week (EW) 13, cases of ALRTI due to PIV and AV were recorded; in EW 29, there was 1 case of bronchiolitis due to AV and rhinovirus (RV), followed by isolated cases of RV; no ALRTI due to RSV or FLU was recorded. In total, 9 cases of ALRTI due to COVID-19 were recorded: 2 moderate bronchiolitis and 7 focal pneumonia; 1 adolescent with comorbidities died due to COVID-19 pneumonia. In 2020, patients were older and had more comorbidities and prior hospitalizations compared to 2019. Focal pneumonia prevailed. Conclusion. In 2020, the rate of hospitalization due to ALRTI decreased significantly compared to 2019,with the absence of seasonal respiratory virus circulation in the pediatric population.

Impact of COVID-19 on the circulation of respiratory viruses in a children's hospital: an expected absence. / Impacto del COVID-19 en la circulación de virus respiratorios en un hospital pediátrico: una ausencia esperada.

INTRODUCTION: Respiratory viruses are the main cause of acute lower respiratory tract infection (ALRTI) in the pediatric population. In March 2020, the World Health Organization declared that the new coronavirus disease 2019 (COVID-19) had reached the pandemic status. Our objective was to describe the impact of COVID-19 pandemic on hospitalizations due to ALRTI at Hospital de Niños Ricardo Gutiérrez (HNRG) and virus circulation. METHODS: Observational, retrospective, and descriptive study of patients hospitalized due to ALRTI comparing 2019 and 2020. RESULTS: In 2020, the rate of hospitalization due to ALRTI decreased by 73%. In 2019, 517 patients with ALRTI were hospitalized; the following viruses were identified in 174: respiratory syncytial virus (RSV) (71.2%), adenovirus (AV) (10.3%), parainfluenza virus (PIV) (9.7%), and influenza virus (FLU) (8.6%). In 2020, 94 patients with ALRTI were hospitalized. Until epidemiological week (EW) 13, cases of ALRTI due to PIV and AV were recorded; in EW 29, there was 1 case of bronchiolitis due to AV and rhinovirus (RV), followed by isolated cases of RV; no ALRTI due to RSV or FLU was recorded. In total, 9 cases of ALRTI due to COVID-19 were recorded: 2 moderate bronchiolitis and 7 focal pneumonia; 1 adolescent with comorbidities died due to COVID-19 pneumonia. In 2020, patients were older and had more comorbidities and prior hospitalizations compared to 2019. Focal pneumonia prevailed. CONCLUSIONS: In 2020, the rate of hospitalization due to ALRTI decreased significantly compared to 2019, with the absence of seasonal respiratory virus circulation in the pediatric population.

Introducción. Los virus respiratorios son la principal causa de infección respiratoria aguda baja (IRAB) en la población pediátrica. En marzo de 2020, la Organización Mundial de la Salud declaró el estado de pandemia de la enfermedad por el nuevo coronavirus 2019 (COVID-19) con un impacto global elevado. El objetivo de este estudio fue describir el impacto de la pandemia de COVID-19 en las internaciones por IRAB en el Hospital de Niños Ricardo Gutiérrez (HNRG) y la circulación viral. Métodos. Estudio observacional, retrospectivo y descriptivo de pacientes internados por IRAB, comparando los años 2019 y 2020. Resultados. En 2020, la tasa de hospitalización por IRAB se redujo un 73 % en el HNRG (575,1/10 000 en 2019 y 155,3/10 000 en 2020). En 2019 se internaron 517 pacientes con IRAB; en 174 se identificaron los virus: sincicial respiratorio (71,2%), adenovirus (AV) (10,3%), parainfluenza (PIF) (9,7 %) e influenza (FLU) (8,6 %). En 2020, se hospitalizaron 94 pacientes con IRAB. Hasta la semana epidemiológica (SE) 13 se registraron casos de IRAB por PIF y AV; en la SE 29 un caso de bronquiolitis por AV y rinovirus (RV), seguido de casos aislados de RV; no hubo IRAB por VSR ni por FLU. Se registraron 9 casos de IRAB por COVID-19: 2 bronquiolitis moderadas y 7 neumonías focales; con un adolescente fallecido por neumonía por COVID-19 con comorbilidades. En 2020, los casos presentaron mayor edad, más comorbilidades e internaciones previas en comparación con el 2019. La neumonía focal fue la presentación clínica predominante. Conclusión. En 2020, la tasa de hospitalización por IRAB se redujo significativamente en comparación con el año anterior, con ausencia de circulación de virus respiratorios estacionales en la población asistida en nuestro centro.

RSV reemergence in Argentina since the SARS-CoV-2 pandemic.

INTRODUCTION: The community mitigation measures taken because of the COVID-19 pandemic had side effects on the circulation of the most frequent respiratory viruses during 2020. In the case of respiratory syncytial virus (RSV), an important paediatric pathogen, a decrease in the number of cases and delayed outbreaks was previously described. AIM AND METHODS: The genetic characteristics of the RSV circulating strains in paediatric patients in Buenos Aires, Argentina before and during the COVID-19 pandemic were studied. RSV (+) samples taken from hospitalised patients with respiratory tract infections (2018- 2021) were analysed through G gene sequencing and evolutionary analyses. RESULTS: No RSV hospitalised paediatric patients were registered in Buenos Aires during 2020; however, RSV reemerged in 2021 with a lower number of cases and a delayed outbreak, peaking in July-August. A total of 147 G gene sequences were analysed. RSV-B (N = 85) predominated during 2018 and 2021 whereas in 2019 RSV-A were more prevalent (N = 62). All RSV-A sequences were ON1-like strains, and all RSV-B were BA-like. Phylogenetic analyses showed that the same genetic lineages circulated before and after 2020, but RSVs from 2021 corresponded to new viral introductions rather than cryptic circulation of the previous genetic clusters in Buenos Aires during 2020. CONCLUSIONS: Following the reopening of borders, the reemergence of RSV in Argentina brought new viral introductions from other countries. Therefore, it is important to continue a deep global molecular surveillance to characterise RSV strains in post-pandemic circulation with an impact in future vaccine implementation.

Severe acute respiratory syndrome Coronavirus 2. Seroepidemiology study in Argentinian slum / Estudio seroepidemiológico de enfermedad por Coronavirus 2019 en un barrio de Argentina

Abstract Most countries in Latin America have already reported thousands of confirmed cases and vulnerable populations are the most affected by the coronavirus disease 2019 (COVID-19) pandemic. Preventive measures such as hygiene, social distancing, and isolation, essential to stop the spread of coronavirus, are difficult to accomplish for vulnerable populations due to their living conditions. Seroepidemiological surveys are assets to measure the transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until July 1st, the incidence rate of SARS-CoV-2 infection in Barrio Padre Mugica, one of the largest slums in Buenos Aires City, was 5.9%. This study aimed to establish the prevalence of SARS-CoV-2 antibodies immunoglobulin G (IgG) immediately after the outbreak, and to identify neighbourhood, household and individual factors associated with seroconversion. The prevalence based on IgG was 53.4% (95% CI 52.8% to 54.1%). For each polymerase chain reaction (RT-qPCR) confirmed case, nine people tested IgG positive, indicating a high rate of undetected (probably asymptomatic) infections. Hence, the high rate of undiagnosed people suggests that clinical criteria and epidemiological nexus should be considered. The high seroprevalence observed in the context of an intense epidemic in a vulnerable area might serve as a reference to other countries. This study contributes to future decision making by understanding population immunity against SARS-CoV2 and its relation to living conditions and foccus that comprehensive biosocial, household-level interventions are needed.

Resumen Muchos países de América Latina han informado miles de casos confirmados y las poblaciones vulnerables son las más afectadas por la pandemia de la enfermedad por coronavirus 2019 (COVID-19). Las medidas preventivas como la higiene, el distanciamiento social y el aislamiento, fundamentales para frenar la propagación del coronavirus, son difíciles de lograr en estas poblaciones debido a sus condiciones de vida. Los estudios seroepidemiológicos son de gran utilidad para medir la transmisión del síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2). Hasta el 1 de julio, la tasa de incidencia de la infección por SARS-CoV-2 en el Barrio Padre Mugica, uno de los barrios marginales más grandes de la ciudad de Buenos Aires, era del 5.9%. Este estudio tuvo como objetivo estimar la prevalencia de anticuerpos inmunoglobulina G (IgG) para SARS-CoV-2 inmediatamente después del brote, e identificar factores del barrio, hogar e individuales asociados con la seroconversión. La prevalencia basada en IgG fue del 53.4% (IC del 95%: 52.8% a 54.1%). Para cada caso confirmado por reacción en cadena de la polimerasa (RT-qPCR), nueve personas dieron positivo en IgG, lo que indica una alta tasa de infecciones no detectadas y probablemente asintomáticas. La alta tasa de personas no diagnosticadas sugiere que se deben considerar los criterios clínicos y el nexo epidemiológico. La alta seroprevalencia observada en el contexto de una intensa epidemia en una zona vulnerable podría servir de referencia a otros países. Este estudio contribuye a la toma de decisiones futuras al comprender la inmunidad de la población contra el SARS-CoV2 en su relación con las condiciones de vida y por su enfoque en la necesidad de intervenciones integrales a nivel del hogar.

Severe acute respiratory syndrome coronavirus 2019. Seroepidemiology study in Argentinian slum.

Most countries in Latin America have already reported thousands of confirmed cases and vulnerable populations are the most affected by the coronavirus disease 2019 (COVID-19) pandemic. Preventive measures such as hygiene, social distancing, and isolation, essential to stop the spread of coronavirus, are difficult to accomplish for vulnerable populations due to their living conditions. Seroepidemiological surveys are assets to measure the transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until July 1st, the incidence rate of SARS-CoV-2 infection in Barrio Padre Mugica, one of the largest slums in Buenos Aires City, was 5.9%. This study aimed to establish the prevalence of SARS-CoV-2 antibodies immunoglobulin G (IgG) immediately after the outbreak, and to identify neighbourhood, household and individual factors associated with seroconversion. The prevalence based on IgG was 53.4% (95% CI 52.8% to 54.1%). For each polymerase chain reaction (RT-qPCR) confirmed case, nine people tested IgG positive, indicating a high rate of undetected (probably asymptomatic) infections. Hence, the high rate of undiagnosed people suggests that clinical criteria and epidemiological nexus should be considered. The high seroprevalence observed in the context of an intense epidemic in a vulnerable area might serve as a reference to other countries. This study contributes to future decision making by understanding population immunity against SARS-CoV2 and its relation to living conditions and foccus that comprehensive biosocial, household-level interventions are needed.

Muchos países de América Latina han informado miles de casos confirmados y las poblaciones vulnerables son las más afectadas por la pandemia de la enfermedad por coronavirus 2019 (COVID-19). Las medidas preventivas como la higiene, el distanciamiento social y el aislamiento, fundamentales para frenar la propagación del coronavirus, son difíciles de lograr en estas poblaciones debido a sus condiciones de vida. Los estudios seroepidemiológicos son de gran utilidad para medir la transmisión del síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2). Hasta el 1 de julio, la tasa de incidencia de la infección por SARS-CoV-2 en el Barrio Padre Mugica, uno de los barrios marginales más grandes de la ciudad de Buenos Aires, era del 5.9%. Este estudio tuvo como objetivo estimar la prevalencia de anticuerpos inmunoglobulina G (IgG) para SARS-CoV-2 inmediatamente después del brote, e identificar factores del barrio, hogar e individuales asociados con la seroconversión. La prevalencia basada en IgG fue del 53.4% (IC del 95%: 52.8% a 54.1%). Para cada caso confirmado por reacción en cadena de la polimerasa (RT-qPCR), nueve personas dieron positivo en IgG, lo que indica una alta tasa de infecciones no detectadas y probablemente asintomáticas. La alta tasa de personas no diagnosticadas sugiere que se deben considerar los criterios clínicos y el nexo epidemiológico. La alta seroprevalencia observada en el contexto de una intensa epidemia en una zona vulnerable podría servir de referencia a otros países. Este estudio contribuye a la toma de decisiones futuras al comprender la inmunidad de la población contra el SARS-CoV2 en su relación con las condiciones de vida y por su enfoque en la necesidad de intervenciones integrales a nivel del hogar.

Estudio clínico-epidemiológico de las infecciones respiratorias agudas bajas causadas por adenovirus en niños hospitalizados. Diecinueve años de vigilancia epidemiológica activa / Clinical and epidemiological study of acute lower respiratory tract infections caused by adenovirus in hospitalized children. Nineteen years of active epidemiological surveillance

Introducción. La infección respiratoria aguda baja por adenovirus es una importante causa de morbimortalidad en niños. Objetivos: Describir el patrón clínico-epidemiológico y los factores asociados en niños hospitalizados.Métodos. Estudio transversal en niños ingresados por infección respiratoria aguda baja al Hospital de Niños Ricardo Gutiérrez, Buenos Aires, en 2000-2018. El diagnóstico viral se realizó mediante inmunofluorescencia indirecta en secreciones nasofaríngeas. Se compararon características clínico-epidemiológicas de infección por adenovirus con otros virus respiratorios (virus sincicial respiratorio, influenza y parainfluenza). Se utilizó regresión logística múltiple para identificar predictores independientes de infección.Resultados. De 16018 pacientes con infección respiratoria aguda baja, 13545 fueron testeados para virus respiratorios y 6047 (el 45 %) fueron positivos. Adenovirus fue el agente menos frecuente [el 4,4 % (265) de los casos]; presentó una tendencia en descenso durante todo el período estudiado (pico en 2003) y circuló durante todo el año (pico en julio). El 63,8 % eran varones; mediana de edad: 11 meses (rango intercuartílico: 6-20). La presentación clínica más frecuente fue neumonía (el 63 %). El 50 % tenía internaciones previas por causa respiratoria; el 15,6 % eran reingresos; el 58,3 % tenía comorbilidades. El 19,2 % requirió asistencia ventilatoria; el 44 %registró complicaciones. La letalidad fue del 7,7 %. La infección por adenovirus se asoció a edad ≥ 12 meses, sexo masculino, presentación clínica de neumonía, internaciones previas por causas respiratorias y reinternaciones.Conclusiones. Los adenovirus fueron detectados con menor frecuencia que los otros virus respiratorios, aunque presentaron un importante perfil de morbimortalidad

Introduction. Acute lower respiratory tract infection (ALRTI) caused by adenovirus is a major cause of morbidity and mortality in children.Objectives. To describe the clinical and epidemiological pattern and associated factors in hospitalized children.Methods. Cross-sectional study in children admitted due to ALRTI to Hospital de Niños "Ricardo Gutiérrez," in the Autonomous City of Buenos Aires, between 2000 and 2018. Viral diagnosis was done by indirect immunofluorescence in nasopharyngeal secretions. The clinical and epidemiological characteristics of adenovirus infection were compared to other respiratory viruses (respiratory syncytial virus, influenza, and parainfluenza). A multiple logistic regression was done to identify independent predictors of infection.Results. Out of 16 018 patients with ALRTI, 13 545 were tested for respiratory viruses; 6047 (45 %) had a positive result. Adenovirus was the least common agent (4.4 % [265] of cases); it tended towards a reduction over the study period (peak in 2003) and circulated throughout the year (peak in July). In total, 63.8 % of patients were males; median age: 11 months (interquartile range: 6-20). The most common clinical presentation was pneumonia (63 %). Prior admissions due to respiratory conditions were seen in 50 %; 15.6 %were readmissions; 58.3 % had comorbidities. Ventilatory support was required by 19.2 %and complications were recorded in 44 %. The fatality rate was 7.7 %. Adenovirus infection was associated with age ≥ 12 months, male sex, clinical presentation of pneumonia, prior admissions due to respiratory conditions, and readmissions.Conclusions. Adenoviruses were less common than other respiratory viruses, although their morbidity and mortality were important

Clinical and epidemiological study of acute lower respiratory tract infections caused by adenovirus in hospitalized children. Nineteen years of active epidemiological surveillance. / Estudio clínico-epidemiológico de las infecciones respiratorias agudas bajas causadas por adenovirus en niños hospitalizados. Diecinueve años de vigilancia epidemiológica activa.

INTRODUCTION: Acute lower respiratory tract infection (ALRTI) caused by adenovirus is a major cause of morbidity and mortality in children. OBJECTIVES: To describe the clinical and epidemiological pattern and associated factors in hospitalized children. METHODS: Cross-sectional study in children admitted due to ALRTI to Hospital de Niños "Ricardo Gutiérrez," in the Autonomous City of Buenos Aires, between 2000 and 2018. Viral diagnosis was done by indirect immunofluorescence in nasopharyngeal secretions. The clinical and epidemiological characteristics of adenovirus infection were compared to other respiratory viruses (respiratory syncytial virus, influenza, and parainfluenza). A multiple logistic regression was done to identify independent predictors of infection. RESULTS: Out of 16 018 patients with ALRTI, 13 545 were tested for respiratory viruses; 6047 (45 %) had a positive result. Adenovirus was the least common agent (4.4 % [265] of cases); it tended towards a reduction over the study period (peak in 2003) and circulated throughout the year (peak in July). In total, 63.8 % of patients were males; median age: 11 months (interquartile range: 6-20). The most common clinical presentation was pneumonia (63 %). Prior admissions due to respiratory conditions were seen in 50 %; 15.6 % were readmissions; 58.3 % had comorbidities. Ventilatory support was required by 19.2 % and complications were recorded in 44 %. The fatality rate was 7.7 %. Adenovirus infection was associated with age ≥ 12 months, male sex, clinical presentation of pneumonia, prior admissions due to respiratory conditions, and readmissions. CONCLUSIONS: Adenoviruses were less common than other respiratory viruses, although their morbidity and mortality were important.

Introducción. La infección respiratoria aguda baja por adenovirus es una importante causa de morbimortalidad en niños. Objetivos: Describir el patrón clínicoepidemiológico y los factores asociados en niños hospitalizados. Métodos. Estudio transversal en niños ingresados por infección respiratoria aguda baja al Hospital de Niños Ricardo Gutiérrez, Buenos Aires, en 2000-2018. El diagnóstico viral se realizó mediante inmunofluorescencia indirecta en secreciones nasofaríngeas. Se compararon características clínico-epidemiológicas de infección por adenovirus con otros virus respiratorios (virus sincicial respiratorio, influenza y parainfluenza). Se utilizó regresión logística múltiple para identificar predictores independientes de infección. Resultados. De 16018 pacientes con infección respiratoria aguda baja, 13545 fueron testeados para virus respiratorios y 6047 (el 45 %) fueron positivos. Adenovirus fue el agente menos frecuente [el 4,4 % (265) de los casos]; presentó una tendencia en descenso durante todo el período estudiado (pico en 2003) y circuló durante todo el año (pico en julio). El 63,8 % eran varones; mediana de edad: 11 meses (rango intercuartílico: 6-20). La presentación clínica más frecuente fue neumonía (el 63 %). El 50 % tenía internaciones previas por causa respiratoria; el 15,6 % eran reingresos; el 58,3 % tenía comorbilidades. El 19,2 % requirió asistencia ventilatoria; el 44 % registró complicaciones. La letalidad fue del 7,7 %. La infección por adenovirus se asoció a edad ≥ 12 meses, sexo masculino, presentación clínica de neumonía, internaciones previas por causas respiratorias y reinternaciones. Conclusiones. Los adenovirus fueron detectados con menor frecuencia que los otros virus respiratorios, aunque presentaron un importante perfil de morbimortalidad.

Toward unified molecular surveillance of RSV: A proposal for genotype definition.

BACKGROUND: Human respiratory syncytial virus (RSV) is classified into antigenic subgroups A and B. Thirteen genotypes have been defined for RSV-A and 20 for RSV-B, without any consensus on genotype definition. METHODS: We evaluated clustering of RSV sequences published in GenBank until February 2018 to define genotypes by using maximum likelihood and Bayesian phylogenetic analyses and average p-distances. RESULTS: We compared the patterns of sequence clustering of complete genomes; the three surface glycoproteins genes (SH, G, and F, single and concatenated); the ectodomain and the 2nd hypervariable region of G gene. Although complete genome analysis achieved the best resolution, the F, G, and G-ectodomain phylogenies showed similar topologies with statistical support comparable to complete genome. Based on the widespread geographic representation and large number of available G-ectodomain sequences, this region was chosen as the minimum region suitable for RSV genotyping. A genotype was defined as a monophyletic cluster of sequences with high statistical support (≥80% bootstrap and ≥0.8 posterior probability), with an intragenotype p-distance ≤0.03 for both subgroups and an intergenotype p-distance ≥0.09 for RSV-A and ≥0.05 for RSV-B. In this work, the number of genotypes was reduced from 13 to three for RSV-A (GA1-GA3) and from 20 to seven for RSV-B (GB1-GB7). Within these, two additional levels of classification were defined: subgenotypes and lineages. Signature amino acid substitutions to complement this classification were also identified. CONCLUSIONS: We propose an objective protocol for RSV genotyping suitable for adoption as an international standard to support the global expansion of RSV molecular surveillance.

Acute Flaccid Myelitis Associated with Enterovirus D68 in Children, Argentina, 2016.

After a 2014 outbreak of severe respiratory illness caused by enterovirus D68 in the United States, sporadic cases of acute flaccid myelitis have been reported worldwide. We describe a cluster of acute flaccid myelitis cases in Argentina in 2016, adding data to the evidence of association between enterovirus D68 and this polio-like illness.

An optimized methodology for whole genome sequencing of RNA respiratory viruses from nasopharyngeal aspirates.

Over the last decade, the number of viral genome sequences deposited in available databases has grown exponentially. However, sequencing methodology vary widely and many published works have relied on viral enrichment by viral culture or nucleic acid amplification with specific primers rather than through unbiased techniques such as metagenomics. The genome of RNA viruses is highly variable and these enrichment methodologies may be difficult to achieve or may bias the results. In order to obtain genomic sequences of human respiratory syncytial virus (HRSV) from positive nasopharyngeal aspirates diverse methodologies were evaluated and compared. A total of 29 nearly complete and complete viral genomes were obtained. The best performance was achieved with a DNase I treatment to the RNA directly extracted from the nasopharyngeal aspirate (NPA), sequence-independent single-primer amplification (SISPA) and library preparation performed with Nextera XT DNA Library Prep Kit with manual normalization. An average of 633,789 and 1,674,845 filtered reads per library were obtained with MiSeq and NextSeq 500 platforms, respectively. The higher output of NextSeq 500 was accompanied by the increasing of duplicated reads percentage generated during SISPA (from an average of 1.5% duplicated viral reads in MiSeq to an average of 74% in NextSeq 500). HRSV genome recovery was not affected by the presence or absence of duplicated reads but the computational demand during the analysis was increased. Considering that only samples with viral load ≥ E+06 copies/ml NPA were tested, no correlation between sample viral loads and number of total filtered reads was observed, nor with the mapped viral reads. The HRSV genomes showed a mean coverage of 98.46% with the best methodology. In addition, genomes of human metapneumovirus (HMPV), human rhinovirus (HRV) and human parainfluenza virus types 1-3 (HPIV1-3) were also obtained with the selected optimal methodology.

Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.