This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023. Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October/2013 to May/2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes. Analyzing 139,625 samples, 5.3% were HRSV-positive (3,008 HRSV-A, 3,882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified. Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.

Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced in Catalonia (Spain, 2023–2024 season onwards) and Italy (2024–2025 season). The United Kingdom (UK) instead introduced maternal RSV vaccination (RSVpreF) in the 2024–2025 season. Our aim was to analyse emergency department (ED) attendances and admissions to hospital following RSVpreF and nirsevimab introduction, with hospitals in Iceland and Romania, where no intervention was introduced, used as comparators. Multi-national retrospective analysis of ED attendances and admissions for all diagnoses, respiratory diagnoses excluding bronchiolitis, and bronchiolitis from all hospitals in Catalonia (Spain), four UK hospitals (Bristol, Edinburgh, Glasgow, and Leicester), and one hospital in Italy (Rome), Romania (Bucharest), and Iceland (Reykjavík) from April 2018 to March 2025. Bronchiolitis diagnoses in the 2024–2025 season were compared to previous pre-intervention seasons (2018–2023, excluding the 2020–2021 COVID-19 year) by applying a generalised linear model in Poisson regression to obtain risk ratios (RR) and 95% confidence intervals (95% CI). In the 2024–2025 season, in Catalonia, there was a reduction in the RR for bronchiolitis ED attendances and admissions in infants of age <6 months (RR 0.45; 95% CI 0.43–0.47 and RR 0.40; 95% CI 0.37–0.43, respectively). This was not seen in Rome, where the RR for ED attendances with bronchiolitis in infants of age <6 months was 1.09 (95% CI 0.92–1.30) and the RR for admissions was 1.12 (95% CI 0.83–1.52). In the UK, for infants of age <6 months with bronchiolitis, there was a significant but modest reduction in 1 out of 4 hospitals for ED attendances (Leicester; RR 0.91, 95% CI 0.85–0.97) and in 2 out of 4 hospitals for admissions (Leicester; RR 0.80, 95% CI 0.69–0.94 and Edinburgh; RR 0.85, 95% CI 0.76–0.95). In Catalonia, there was a sustained reduction in bronchiolitis ED attendances and admissions for infants in the 2024–2025 season. However, no substantial reduction in bronchiolitis ED attendances or admissions was observed in Rome or the UK. These differences are likely to relate to the reduced uptake of RSV prevention products in these settings compared to Catalonia. None.

To evaluate the effect of the selective pressure exerted by nirsevimab on human respiratory syncytial virus (HRSV) in Catalonia (2023-2024) by analysing viral mutations, diversity, and evolutionary dynamics, based on viruses characterised from non-immunised and previously immunised patients. Respiratory samples were collected through the SIVIC sentinel network and three hospitals in Catalonia. HRSV-positive samples underwent whole-genome sequencing (WGS), or F gene sequencing when WGS was not feasible. Viral diversity, phylogenetics, and selection pressure were assessed. A total of 251 WGS (HRSV-A: 165; HRSV-B: 86) and 27 F gene sequences (HRSV-A: 13; HRSV-B: 14) were obtained for the non-immunised group. For immunised cases, 79 WGS (HRSV-A: 67; HRSV-B: 12) and 12 F sequences (HRSV-A: 10; HRSV-B: 2) were analysed. Lineage distribution remained similar between groups. Nucleotide diversity was similar for HRSV-A groups, though reduced in immunised HRSV-B. Selection pressure analyses suggested a shift toward neutral evolution in immunised samples. Mutations N63S, K65R, I206T, and K209E (HRSV-A) and K68E, R209Q, and S211N (HRSV-B) were detected in nirsevimab epitope, with K209E and K68E absent in non-immunised samples. Nirsevimab immunisation may influence HRSV evolution, particularly in HRSV-B. Continued genomic surveillance is crucial for early mAb-resistant mutants detection.

(1) Background: Respiratory viral infections, including those caused by SARS-CoV-2, respiratory syncytial virus (RSV), influenza viruses, rhinovirus, and adenovirus, are major causes of acute respiratory infections (ARIs) in children. Symptom-based predictive models are valuable tools for expediting diagnoses, particularly in primary care settings. This study assessed the effectiveness of machine learning-based models in estimating infection probabilities for these common pediatric respiratory viruses, using symptom data. (2) Methods: Data were collected from 868 children with ARI symptoms evaluated across 14 primary care centers, members of COPEDICAT (Coronavirus Pediatria Catalunya), from October 2021 to October 2023. Random forest and boosting models with 10-fold cross-validation were used, applying SMOTE-NC to address class imbalance. Model performance was evaluated via area under the curve (AUC), sensitivity, specificity, and Shapley additive explanations (SHAP) values for feature importance. (3) Results: The model performed better for RSV (AUC: 0.81, sensitivity: 0.64, specificity: 0.77) and influenza viruses (AUC: 0.71, sensitivity: 0.70, specificity: 0.59) and effectively ruled out SARS-CoV-2 based on symptom absence, such as crackles and wheezing. Predictive performance was lower for non-enveloped viruses like rhinovirus and adenovirus, due to their nonspecific symptom profiles. SHAP analysis identified key symptoms patterns for each virus. (4) Conclusions: The study demonstrated that symptom-based predictive models effectively identify pediatric respiratory infections, with notable accuracy for those caused by RSV, SARS-CoV-2, and influenza viruses.

Background: Herpangina and hand, foot, and mouth disease (HFMD) are common pediatric enterovirus syndromes, but long-term evidence from European primary care remains scarce. Methods: Primary care electronic health records from the public healthcare system in Catalonia, Spain, were retrospectively analyzed for the academic years 2014–2015 to 2024–2025 using International Classification of Diseases, 10th revision codes. Incidence trends, age and sex patterns, seasonal peak timing, and peak-to-peak dependence were assessed in children younger than 5 years. Results: A total of 137,460 diagnoses were identified, including 54,060 herpangina and 83,400 HFMD. Both syndromes showed recurrent bimodal seasonality aligned with school holidays. Peak magnitudes were negatively correlated at both 6-month and 1-year lags, consistent with susceptible depletion and replenishment. Before the pandemic, spring herpangina peaks shifted about 1.5 weeks later for each 1-week delay in Easter. Incidence declined sharply in 2020 and rebounded from autumn 2021, particularly for HFMD. Most diagnoses occurred in children aged 1–2 years, with a transient post-pandemic shift toward ages 3–4 years in the first post-pandemic season. Age-specific curves were highly synchronized, with no pediatric age group consistently preceding the others. Conclusions: This large primary care series, among the very few long-term European studies of herpangina and HFMD, supports structured seasonal dynamics shaped by school-calendar timing and susceptible dynamics over successive seasons. Long-term primary care surveillance may help interpret atypical transmission patterns and support pediatric preparedness when virologic surveillance is limited.

Introduction: Invasive aspergillosis (IA) represents one of the most frequent invasive fungal infections in paediatric patients with risk factors. An increase in cases of azole‐resistant IA has been reported in adult patients. The aim of this study is to present a series of 11 cases of paediatric patients with this pathology. Methods: A retrospective descriptive study including paediatric patients with probable or proven azole‐resistant IA treated between January 2019 and June 2024 in four tertiary hospitals in Spain. Results: Eleven cases are reported, all patients with risk factors for IA, mainly with haematopoietic stem cell transplantation (HCT) due to haematological malignancies and heart transplant in the early post‐transplant period. These patients represent 22% of all proven or probable paediatric IA cases ( n = 50) diagnosed in the study centres during the period. Five were previously receiving azole‐based antifungal prophylaxis. The most frequently isolated species was Aspergillus fumigatus . Despite receiving at least partially active antifungals plus adjunctive treatment therapy from diagnosis, attributable mortality was high (8/11 patients). Conclusion: Azole‐resistant IA should be suspected in paediatric patients with risk factors, especially if they show poor clinical course or have received azole prophylaxis. The performance of invasive tests, as well as species identification and resistance testing, is essential to optimise treatment. In breakthrough IA it should be considered empirical treatment with an antifungal from a different class than the one used for prophylaxis, alone or in combination.