Impacte a nivell hospitalari de les infeccions respiratòries virals de vies baixes en la població infantil

A Catalunya hi ha poca informació sobre el consum de recursos sanitaris que impliquen les infeccions respiratòries virals de vies baixes (bronquiolitis, bronquitis, agudització asmàtica i pneumònia) en la població infantil. Un nou estudi ha analitzat l'epidemiologia, els símptomes, la gravetat i el consum de recursos sanitaris d'aquestes infeccions entre 2012 i 2020 a l'Hospital Infantil Vall d'Hebron.En Cataluña existe poca información sobre el consumo de recursos sanitarios que implican las infecciones respiratorias virales de vías bajas (bronquiolitis, bronquitis, agudización asmática y neumonía) en la población infantil. Un nuevo estudio ha analizado la epidemiología, los síntomas, la gravedad y el consumo de recursos sanitarios de estas infecciones entre 2012 y 2020 en el Hospital Infantil Vall d'Hebron.In Catalonia, information is scarce about the in-hospital burden of diseases involving viral lower respiratory tract infections (bronchiolitis, bronchitis, asthma exacerbation and pneumonia) in paediatric population. A new study has analyzed the epidemiology, the symptoms, the severity and the economical features of these infections between 2012 and 2020 at the Children's Hospital in Vall d'Hebron Barcelona Hospital Campus

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

Acute flaccid myelitis; Enterovirus D68; SurveillanceMielitis flàcida aguda; Enterovirus D68; VigilànciaMielitis flácida aguda; Enterovirus D68; VigilanciaWe report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe

The emergence, impact, and evolution of human metapneumovirus variants from 2014 to 2021 in Spain

Epidemiology; Human metapneumovirus; Whole-genome sequencingEpidemiologia; Metapneumovirus humà; Seqüenciació del genoma completEpidemiología; Metapneumovirus humano; Secuenciación del genoma completoBackground Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and evolutionary dynamics of HMPV. Methods Laboratory-confirmed HMPV were characterised based on partial-coding G gene sequences with MEGA.v6.0. WGS was performed with Illumina, and evolutionary analyses with Datamonkey and Nextstrain. Results HMPV prevalence was 2.5%, peaking in February-April and with an alternation in the predominance of HMPV-A and –B until the emergence of SARS-CoV-2, not circulating until summer and autumn-winter 2021, with a higher prevalence and with the almost only circulation of A2c111dup. G and SH proteins were the most variable, and 70% of F protein was under negative selection. Mutation rate of HMPV genome was 6.95 × 10-4 substitutions/site/year. Conclusion HMPV showed a significant morbidity until the emergence of SARS-CoV-2 pandemic in 2020, not circulating again until summer and autumn 2021, with a higher prevalence and with almost the only circulation of A2c111dup, probably due to a more efficient immune evasion mechanism. The F protein showed a very conserved nature, supporting the need for steric shielding. The tMRCA showed a recent emergence of the A2c variants carrying duplications, supporting the importance of virological surveillance.This study was supported by the European Regional Development Fund (ERDF) "A way to achieve Europe", Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0003], and supported by the Health Research Fund, Spanish Ministry of Economy and Competitiveness [Grant FIS PI18/00685]

The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain): A long-term, clinical, epidemiologic and economic study

Cost of illness; Hospitalization; VirusesCost de la malaltia; Hospitalització; VirusCoste de la enfermedad; Hospitalización; VirusBackground Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. Methods From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. Results A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. Conclusions Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.This work was partially supported by the Spanish National R + D + I Plan 2008–2011 and by the Carlos III Health Institute, the Subdirectorate-General of Networks and Cooperative Research Centers, the Spanish Ministry of Economy and Competitiveness, the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), and by the Health Research Fund, the Spanish Ministry of Economy and Competitiveness (grants FIS PI14/01838 and FIS PI18/00685), and the European Regional Development Fund (ERDF). Editorial assistance for revision of the English language and edition of the manuscript was provided by Vanessa Marfil, medical writer from MSC (Spain) and funded by Sanofi

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe

Epidemiología, aspectos virológicos, clínica, gravedad y consumo de recursos sanitarios de la infección respiratoria viral pediátrica

Introducció: Les infeccions respiratòries de vies baixes (IRVB) virals estan associades a una elevada morbimortalitat a la població pediàtrica i són la principal causa d'hospitalització, especialment en els menors de 2 anys, a causa de la bronquiolitis pel virus respiratori sincicial (VRS). Factors genètics del virus, factors propis de l'hoste i factors ambientals, poden condicionar la gravetat de la bronquiolitis per VRS, una malaltia per a la qual l'únic tractament recomanat i que ha demostrat eficàcia són les mesures de suport. Objectius i Metodologia: Aquesta tesi doctoral s'ha estructurat a partir de tres estudis observacionals, retrospectius i descriptius en població pediàtrica hospitalitzada a l'Hospital Infantil Vall d'Hebron de Barcelona. En el primer estudi hem pogut analitzar l'estacionalitat, clínica, gravetat i consum de recursos sanitaris hospitalaris de les IRVB virals en nens menors de 16 anys entre 2012 i 2020, a partir de les dades estructurades disponibles a la història clínica electrònica del pacient. Al segon treball, realitzat entre les temporades 2014-2015 i 2017-2018 hem estudiat si el subgrup genètic del VRS és un factor condicionant de la clínica i gravetat de la bronquiolitis en menors de 24 mesos. A l'últim treball, hem avaluat l'adherència dels clínics a les recomanacions de diagnòstic i tractament de la bronquiolitis després de l'actualització del protocol de l'hospital el 2015, basat en les darreres guies de pràctica clínica. Resultats i conclusions: Els virus amb més morbiditat per la seva prevalença o gravetat han estat el VRS, els virus de la grip, el metapneumovirus humà i el rinovirus. El VRS és el que s'ha associat a un increment més gran de la probabilitat de patir una bronquiolitis, el rinovirus de patir sibilàncies/aguditzacions asmàtiques i els virus de la grip de patir pneumònia. El virus de la grip A és el que ha causat les hospitalitzacions més prolongades i el VRS ha estat el principal virus associat als ingressos a la unitat de cures intensives (UCI). Aquestes malalties s'han associat a una elevada ocupació de llits hospitalaris, tant de plantes convencionals com de crítics, i a un alt consum de recursos sanitaris, especialment durant les temporades epidèmiques. Les bronquiolitis per VRS-A han tingut una pitjor evolució durant l'hospitalització en comparació amb el VRS-B, evidenciada per una proporció més gran de pacients amb escales de gravetat moderades-greus a l'ingrés, més proporció de pacients amb estada hospitalària i a la UCI superior a 7 dies, i major proporció de pacients que ingressen a la UCI i que requereixen ventilació mecànica invasiva. Finalment, pel que fa a l'adaptació de la pràctica clínica a les recomanacions del protocol de bronquiolitis, s'ha evidenciat una reducció significativa en l'ús de salbutamol, adrenalina i sèrum salí hipertònic al 3%; la prescripció de corticoides ha disminuït de manera no significativa. Així mateix, ha disminuït de manera significativa la realització de radiografies de tòrax i la prescripció d'antibiòtics. Com preveiem, aquests canvis a la pràctica clínica no han donat lloc a una pitjor evolució dels pacients.Introducción: Las infecciones respiratorias de vías bajas (IRVB) virales están asociadas a una elevada morbimortalidad en la población pediátrica y son la principal causa de hospitalización, especialmente en los menores de 2 años, debido a la bronquiolitis por el virus respiratorio sincitial (VRS). Factores genéticos del virus, factores propios del huésped y ambientales, pueden condicionar la gravedad de la bronquiolitis por VRS, una enfermedad para la que el único tratamiento recomendado y que ha demostrado eficacia son las medidas de soporte. Objetivos y Metodología: La presente tesis doctoral se ha estructurado a partir de tres estudios observacionales, retrospectivos y descriptivos en población pediátrica hospitalizada en el Hospital Infantil Vall d&#8217;Hebron de Barcelona. En el primer estudio hemos podido analizar la estacionalidad, clínica, gravedad y consumo de recursos sanitarios hospitalarios de las IRVB virales en niños menores de 16 años entre 2012 y 2020, a partir de los datos estructurados disponibles en la historia clínica electrónica del paciente. En el segundo trabajo, realizado entre las temporadas 2014-2015 y 2017-2018 hemos estudiado si el subgrupo genético del VRS es un factor condicionante de la clínica y gravedad de la bronquiolitis en menores de 24 meses. En el último trabajo, hemos evaluado la adherencia de los clínicos a las recomendaciones de diagnóstico y tratamiento de la bronquiolitis tras la actualización del protocolo del hospital en 2015, basado en las últimas guías de práctica clínica. Resultados y conclusiones: Los virus con mayor morbilidad por su prevalencia o gravedad han sido el VRS, los virus de la gripe, el metapneumovirus humano y el rinovirus. El VRS ha sido el que se asocia a un mayor incremento de la probabilidad de sufrir una bronquiolitis, el rinovirus de sufrir sibilancias/agudizaciones asmáticas y los virus de la gripe de sufrir neumonía. El virus de la gripe A es el que ha causado las hospitalizaciones más prolongadas y el VRS ha sido el principal virus asociado a los ingresos en la unidad de cuidados intensivos (UCI). Estas enfermedades se han asociado a una elevada ocupación de camas de hospitalización, tanto convencionales como de críticos, y a un alto consumo de recursos sanitarios, especialmente durante las temporadas epidémicas. Las bronquiolitis por VRS-A han tenido una peor evolución durante la hospitalización en comparación con el VRS-B, evidenciada por una mayor proporción de pacientes con escalas de gravedad moderadas-graves al ingreso, mayor proporción de pacientes con estancia hospitalaria y en UCI superior a 7 días, y mayor proporción de pacientes que ingresan en UCI y que requieren ventilación mecánica invasiva. Finalmente, en relación a la adaptación de la práctica clínica a las recomendaciones del protocolo de bronquiolitis, se ha evidenciado una reducción significativa en el uso de salbutamol, adrenalina y suero salino hipertónico al 3%; la prescripción de corticoides ha disminuido de forma no significativa. Así mismo, ha disminuido de forma significativa la realización de radiografías de tórax y la prescripción de antibióticos. Como preveíamos, estos cambios en la práctica clínica no han dado lugar a una peor evolución de los pacientes.Introduction: Viral lower respiratory tract infections (LRTIs) are associated with high morbidity and mortality in the pediatric population and are the main cause of hospitalization, especially in children under 2 years of age, due to respiratory syncytial virus (RSV) bronchiolitis. Genetic factors of the virus, host and environmental factors, can condition the severity of RSV bronchiolitis, a disease for which the only recommended treatment and that has proven efficacy are supportive measures. Objectives and Methodology: This doctoral thesis has been structured from three observational, retrospective and descriptive studies in the pediatric population hospitalized at the Vall d'Hebron Children's Hospital in Barcelona. In the first study, we were able to analyze the seasonality, symptoms, severity, and consumption of hospital healthcare resources of viral LRTIs in children under 16 years of age between 2012 and 2020, based on the structured data available in the patient's electronic medical record. In the second study, carried out between the 2014-2015 and 2017-2018 seasons, we have studied whether the RSV genetic subgroup is a determining factor in the symptoms and severity of bronchiolitis in children under 24 months of age. In the last study, we have evaluated the adherence of clinicians to the recommendations for the diagnosis and treatment of bronchiolitis after the update of the hospital protocol in 2015, based on the latest clinical practice guidelines. Results and conclusions: The viruses with the highest morbidity due to their prevalence or severity have been RSV, influenza viruses, human metapneumovirus and rhinovirus. RSV has been associated with the greatest increase in the probability of suffering from bronchiolitis, rhinovirus with wheezing/asthmatic exacerbations, and influenza viruses with pneumonia. The influenza A virus is the one that has caused the longest hospitalizations and RSV has been the main virus associated with intensive care unit (ICU) admissions. These diseases have been associated with a high occupancy of hospital beds, both in the general ward and in the ICU, and a high consumption of healthcare resources, especially during epidemic seasons. RSV-A bronchiolitis has had a worse evolution during hospitalization compared to RSV-B, evidenced by a higher proportion of patients with moderate-severe severity scales on admission, a higher proportion of patients with a hospital and ICU stay longer than 7 days, and a higher proportion of patients admitted to the ICU and requiring invasive mechanical ventilation. Finally, in relation to the adaptation of clinical practice to the recommendations of the bronchiolitis protocol, there has been a significant reduction in the use of salbutamol, adrenaline and 3% hypertonic saline solution; the prescription of corticosteroids has decreased in a non-significant way. Likewise, the performance of chest X-rays and the prescription of antibiotics have significantly decreased. As we expected, these changes in clinical practice have not led to worse patient outcomes.Universitat Autònoma de Barcelona. Programa de Doctorat en Pediatria, Obstetrícia i Ginecologi

Insights into immune evasion of human metapneumovirus: novel 180- and 111-nucleotide duplications within viral G gene throughout 2014-2017 seasons in Barcelona, Spain

9 pags., 4 figs., 6 tabs.Background: Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe its genetic diversity and clinical impact in patients attended at a tertiary university hospital in Barcelona from the 2014-2015 to the 2016-2017 seasons, focusing on the emerging duplications in G gene and their structural properties. Methods: Laboratory-confirmed HMPV were characterised based on partial-coding F and G gene sequences with MEGA.v6.0. Computational analysis of disorder propensity, aggregation propensity and glycosylation sites in viral G predicted protein sequence were carried out. Clinical data was retrospectively reviewed and further associated to virological features. Results: HMPV prevalence was 3%. The 180- and 111-nucleotide duplications occurred in A2c lineage G protein increased in prevalence throughout the study, in addition to short genetic changes observed in other HMPV lineages. The A2c G protein without duplications was calculated to protrude over F protein in 23% of cases and increased to a 39% and a 46% with the 111- and 180-nucleotide duplications, respectively. Children did not seem to be more affected by these mutant viruses, but there was a strong association of these variants to LRTI in adults. Discussion: HMPV presents a high genetic diversity in all lineages. Novel variants carrying duplications might present an evolutionary advantage due to an improved steric shielding, which would have been responsible for the reported increasing prevalence and the association to LRTI in adults.This study was supported by the Spanish Ministry of Economy and Competitiveness (grants BFU2016-78232-P), Instituto de Salud Carlos III and by the European Regional Development Fund, through the Interreg V-A programme: POCTEFA 2014-2020 (grant Pirepred EFA086/15). It was also co-financed by the European Development Regional Fund (ERDF) "A way to achieve Europe", Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003). We also would like to acknowledge the Statistics and Bioinformatics Unit (UEB) in Vall d’Hebron Research Institute (VHIR) for the statistical analyses

The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain) : A long-term, clinical, epidemiologic and economic study

Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods