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Between 2014 and 2018, we evaluated the severity of 687 cases of bronchiolitis caused by respiratory syncytial virus (RSV) in Catalonia, Spain. Compared to RSV-B, RSV-A cases required intensive care (adjusted relative risk (aRR) = 1.44, p < 0.01) and respiratory support (aRR = 1.07, p < 0.01) more often; hospital stay was one day longer (p < 0.01). Subgroup identification may aid clinical evaluation and seasonal healthcare planning.

Background Bronchiolitis caused by the respiratory syncytial virus (RSV) is the main reason for hospitalization in infants. Supportive care is the mainstay of treatment, and tests are restricted to a few indications. During 2015, our hospital bronchiolitis protocol (2015 HBP) was updated according to the latest practice guidelines. Objective The objective of this study was to assess implementation of the 2015 HBP and the clinical outcome of children aged

Cost of illness; Hospitalization; Viruses Cost de la malaltia; Hospitalització; Virus Coste de la enfermedad; Hospitalización; Virus Background 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

Tizanidine is a central alpha-2 adrenergic receptor agonist indicated for the treatment of spasticity in adults; however, its use in the pediatric population is considered off-label. In adults, the dose is gradually titrated until the desired reduction in muscle tone is achieved. Hypotension is a frequent adverse effect, but impaired liver function is not characteristic of alpha-2 adrenergic agonist overdose. We report a 2-year-old male affected with spastic quadriplegia (treated with clonazepam and tizanidine) and dysphagia (he was fed by nasogastric tube). Two days before admission caregivers ran out of clonazepam so they increased the tizanidine dose from 0.15 mg/kg/day to 1.6 mg/kg/day. Simultaneously his nasogastric tube fell out; therefore, he was unable to maintain proper oral nutrition and hydration. He presented to the emergency department hemodynamically unstable, with impaired consciousness and signs of severe dehydration. Blood tests revealed hepatic dysfunction without cholestasis and renal dysfunction. He was transferred to the pediatric intensive care unit. Treatment was mainly supportive, apart from tizanidine discontinuation. Metabolic and infectious diseases were ruled out so he was finally diagnosed as having liver, renal, and cardiovascular failure after tizanidine overdose, worsened by dehydration. His clinical status improved, and after 3 weeks he was discharged from the hospital, receiving clonidine instead of tizanidine to treat spasticity. Tizanidine overdose can result in serious complications that can be worsened because of patient comorbidities.

We observed an unusual pattern of respiratory syncytial virus (RSV) in children under 5 years in Catalonia (Spain). We observed a near absence of RSV during winter months and a subsequent surge during the late spring. Primary care electronic health records combined with hospital RSV laboratory confirmation could be used to monitor trends of respiratory pathogens.

Background Great reductions of respiratory syncytial virus (RSV) in children were observed during the 2020 Southern hemisphere winter. Aim To describe trends of RSV related disease in children in the Northern hemisphere and to propose a low cost clinical surveillance system based on primary care electronic health records (EHR). Methods Time series analysis of RSV-related disease and virus laboratory-confirmations in children under 5 years old from 1 September 2009 to 16 January 2021. We collected RSV diagnoses from primary care EHR in Catalonia (Spain). We compared the trend of RSV in the season 2020-2021 with that in the previous seasons. We estimated the expected RSV cases with data from 2009 to 2018 using a time series regression adjusted by seasonality. We used the same method to estimate the expected RSV laboratory-confirmations as a sensitivity analysis. Results In previous seasons, RSV-related disease peaks in Catalonia during the weeks 52 and 53. However in the 2020-2021 period, we observed a reduction of 87.6% (95% CI: 82.7% to 90.3%) in RSV-related disease from october 2020 compared to the expected. Only 1 RSV case was laboratory-confirmed during the 2020-2021 season until mid-January. Conclusions We observed a nearly absence of RSV-related disease and laboratory-confirmations during the weeks when RSV usually peaks in Catalonia. The use of primary care EHR could be a low-cost surveillance system to monitorize trends of RSV the coming months.

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.

Highlights • The study reports virological and clinical enterovirus surveillance in Catalonia. • Most of neurological studied cases were from the 2016 spring outbreak. • Rhombencephalitis cases were related to EV-A71 infection. • EV-D68 was associated with lower respiratory tract infections. • It is necessary to perform EV surveillance in primary care settings., Background Enterovirus (EV) infections are usually asymptomatic or mild, but symptomatic infections can evolve to severe complications. Outbreaks of EV-A71 and EV-D68 have been recently reported worldwide, sometimes related to severe clinical outcomes. Objective To describe EV genetic diversity and the clinical outcomes from paediatric patients attended at a tertiary university hospital in Barcelona (Catalonia, Spain) from 2014 to 2017. Study design Specimens were collected from paediatric (

Aim: To describe the circulation, genetic diversity and clinical features of human metapneumovirus (HMPV) in pediatric patients that attended the Hospital Universitari Vall d'Hebron, Spain from 2014 to 2016. Materials & methods: Partial G gene was sequenced from laboratory-confirmed HMPV respiratory specimens for subsequent phylogenetic analysis. Results: A total of 121 different samples were HMPV laboratory-confirmed out of 6658 specimens received. The highest circulation was from February to April, with a prevalence of 3%. Different genetic groups within both genotypes were detected at variable levels. A 180-nucleotide duplication was first characterized within the G gene in nine cases, mostly related to lower respiratory-tract infection. Conclusion: This study reported on the circulation of a novel HMPV with a 180-nucleotide duplication in the G gene, but no clinical changes in related cases were observed. Their prevalence increased during the last season suggesting changes in viral features.

Aim: To describe the genetic diversity of enteroviruses (EV) causing hand, foot and mouth disease (HFMD) and herpangina, especially of coxsackievirus (CV)-A6, from patients attended at pediatric primary care centers during the 2017–2018 season. Methods: Phylogenetic analysis of partial VP1 region was performed for genetic characterization. The complete VP1 and 3Dpol proteins were sequenced for lineage determination and detection of recombination events. Results: An 80% of samples were EV laboratory-confirmed. CV-A6 was the most detected (70%) and associated with atypical HFMD (78%). The comparison of VP1 and 3Dpol phylogenies showed evidence of recombination in three strains, in which two shifted to CV-A16 3Dpol. Conclusion: The study provides recent information regarding the nonrecombinant and recombinant EVs related to HFMD at primary care centers.

Aim: Human respiratory syncytial virus (HRSV) is the main cause of respiratory tract infections among infants. Materials & methods: In the present study, the molecular epidemiology of HRSV detected from 2013 to 2017 has been described. Results: A 10% of collected samples were laboratory confirmed for HRSV. Patients under 2 years of age were the main susceptible population to respiratory syncytial virus disease, but an increasingly number of confirmed patients over 65 years of age was reported. Epidemics usually started in autumn and ended in spring. Both HRSV groups co-circulated every season, but the HRSV-B was the most predominant. HRSV-A and HRSV-B strains mainly belonged to ON1 and BA9 genotypes, respectively. Conclusion: The present study reports recent data about the genetic diversity of circulating HRSV in Spain.

Enteroviruses (EVs) and rhinoviruses (RVs) belong to the Enterovirus genus within the Picornaviridae family, and show genetic similarities. These viruses are related to mild diseases, but EVs infections can sometimes lead to more severe complications. Current diagnostic molecular techniques should discriminate between the four EV and the three RV species that infect humans. The aim was to revise the EV and RV PCR-confirmed specimens by sequencing for genetic characterisation.Respiratory tract specimens were collected from patients with suspicion of respiratory infection. Respiratory viruses' laboratory-confirmation was performed by commercial multiplex real-time RT-PCR assays. Genetic characterisation of all EV and in a selection of RV was performed based on the phylogenetic analyses of partial VP1 and VP4/2 sequences, respectively.From 19,957 tested specimens, 309 (1.5%) were EV-positive, 2546 (12%) were RV-positive, and 233 (1%) were EV/RV co-detections. The phylogenetic analyses revealed that: among single EV detections, 177/309 (57%) were characterised as EV, 2/309 (1%) as RV, and 130/309 (42%) could not be typed; among single 1771 RV detections (Ct 35), 1651/1771 (93%) were characterised as RV, 3/1771 (0.3%) as EV and 117/1771 (6.7%) could not be typed. Among EV/RV co-detections, 62/233 (27%) were characterised as EV, 130/233 (56%) as RV and 41/233 (18%) could not be typed.A diagnostic method well considered for routine laboratory-confirmation of respiratory viruses should discriminate EV and RV targets. RVs are usually associated with mild respiratory disease, but the potential relatedness of EVs to neurological complications makes their monitoring mandatory. Therefore, an accurate detection and differentiation should be required in commercial diagnostic solutions.

Acute flaccid myelitis; Enterovirus D68; Surveillance Mielitis flàcida aguda; Enterovirus D68; Vigilància Mielitis flácida aguda; Enterovirus D68; Vigilancia 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.