Impact of the COVID-19 pandemic on the epidemiology of bronchiolitis at Hôpital du Jura in Delémont, Switzerland: a retrospective observational study.

BACKGROUND: Non-pharmaceutical interventions during the COVID-19 pandemic caused an unusual epidemiology in bronchiolitis hospitalisations, with a peak in the summer seasons of 2020 and 2021. AIM: The aim of this study was to analyse data from a 5-year period (2018-2022) at Hôpital du Jura in Delémont, Switzerland, regarding bronchiolitis hospitalisations before, during and towards the end of the COVID-19 pandemic in order to prepare for future changes in bronchiolitis epidemiology. MATERIALS AND METHODS: Anonymous retrospective data on bronchiolitis hospitalisations for children under 2 years of age with hospital admission date from 1 January 2018 to 31 December 2022 was obtained from the Health Records Coding Unit of our hospital. RESULTS: A clear shift in the peak of bronchiolitis is seen in 2021 compared to the three previous years. Starting in spring 2022, the trend begins to mimic pre-pandemic years. For respiratory syncytial virus (RSV) bronchiolitis hospitalisations specifically, an important peak in hospitalisations is seen in the summer months of 2021, with over 20 admissions, compared to zero admissions in the previous years. This peak shifts to the winter months in 2022. CONCLUSIONS: The non-pharmacological interventions implemented during 2020 and early 2021 did not cause a long-lasting seasonal shift in bronchiolitis. In 2022, when the non-pharmacological interventions were no longer in place in the non-hospital setting, the peak of bronchiolitis hospitalisations is seen once again in the winter months. We predict that hospitalisation patterns will gradually revert to those of pre-pandemic years.

Distinct clinical characteristics of bocavirus and Mycoplasma pneumoniae infection in children plastic bronchitis.

BACKGROUND: This study investigated clinical and laboratory characteristics of human bocavirus type 1 (HBoV1)-plastic bronchiolitis (PB), Mycoplasma pneumoniae (MP)-associated plastic bronchitis (PB) and MP-NPB in children, highlighting inflammation, coagulation, and bronchoscopic needs. METHODS: Data on preschool children with PB during HBoV1 or MP infection were collected, comparing MP-PB to severe Mycoplasma pneumoniae pneumonia. RESULT: Compared with the MP-PB group, the HBoV1-PB group, with younger children, had significantly milder clinical symptoms but higher WBC counts (p = .028). The MP-PB group exhibited notably elevated Fibrinogen (p = .045) and d-dimer levels (p < .001). When contrasting the MP-PB with the MP-NPB group, children in MP-PB group still had higher levels of d-dimer and increased inflammatory indicators such as C-reactive protein, procalcitonin, lactate dehydrogenase, and interleukin-6, which were significantly elevated compared with the MP-NPB group. MP-PB showed a higher prevalence of plastic bronchial casts in lower lobes (p = .016) and a dominance of neutrophils in BALF cytology. Additionally, children in the MP-PB group tended to undergo a greater number of bronchoscopies. CONCLUSION: This study identifies key differences in plastic bronchitis in children due to HBoV1 and MP, highlighting HBoV1's milder inflammation in younger kids and MP's link to severe inflammatory and coagulation responses, guiding clinical diagnosis and treatment.

Disease Burden of RSV Infections and Bronchiolitis in Young Children (< 5 Years) in Primary Care and Emergency Departments: A Systematic Literature Review.

Respiratory syncytial virus (RSV) is the most common cause of acute respiratory infections in young children. Limited data are available on RSV disease burden in primary care and emergency departments (EDs). This review synthesizes the evidence on population-based incidence rates of RSV infections in young children (< 5 years) in primary care and EDs. A systematic literature review was performed in PubMed and Embase. Studies reporting yearly population-based RSV incidence rates in primary care and EDs were included. A total of 4244 records were screened and 32 studies were included, conducted between 1993 and 2019. Studies were mainly performed in high-income countries (n = 27), with 15 studies in North America and 10 studies in Europe. There was significant variability in study methodology and setting among studies, resulting in considerable variability in reported incidence rates. Incidence rates were higher in primary care-ranging from 0.8 to 330 (median = 109) per 1000 population-compared to EDs (7.5-144.0, median = 48). The highest incidence rates were reported in infants. Additionally, incidence rates were higher in high-income countries and in studies using laboratory-confirmed RSV cases compared to studies using bronchiolitis ICD-codes (non-laboratory confirmed). Our study found that a substantial number of children under 5 years of age attend primary care settings and EDs, every year for RSV infections. Due to the considerable heterogeneity in study methodology, it was impossible to draw definitive conclusions regarding factors explaining differences in reported incidence rates. Additionally, more studies in low- and middle-income countries are recommended.

Integrated-omics analysis with explainable deep networks on pathobiology of infant bronchiolitis.

Bronchiolitis is the leading cause of infant hospitalization. However, the molecular networks driving bronchiolitis pathobiology remain unknown. Integrative molecular networks, including the transcriptome and metabolome, can identify functional and regulatory pathways contributing to disease severity. Here, we integrated nasopharyngeal transcriptome and metabolome data of 397 infants hospitalized with bronchiolitis in a 17-center prospective cohort study. Using an explainable deep network model, we identified an omics-cluster comprising 401 transcripts and 38 metabolites that distinguishes bronchiolitis severity (test-set AUC, 0.828). This omics-cluster derived a molecular network, where innate immunity-related metabolites (e.g., ceramides) centralized and were characterized by toll-like receptor (TLR) and NF-κB signaling pathways (both FDR < 0.001). The network analyses identified eight modules and 50 existing drug candidates for repurposing, including prostaglandin I2 analogs (e.g., iloprost), which promote anti-inflammatory effects through TLR signaling. Our approach facilitates not only the identification of molecular networks underlying infant bronchiolitis but the development of pioneering treatment strategies.

Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear. METHODS: In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA). RESULTS: In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, PCM1 for the microtubule anchoring module, LIMS1 for the cell-substrate junction module. CONCLUSIONS: In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

A randomized, embedded, pragmatic, Bayesian clinical trial examining clinical decision support for high flow nasal cannula management in children with bronchiolitis: design and statistical analysis plan.

BACKGROUND: High flow nasal cannula (HFNC) has been increasingly adopted in the past 2 decades as a mode of respiratory support for children hospitalized with bronchiolitis. The growing use of HFNC despite a paucity of high-quality data regarding the therapy's efficacy has led to concerns about overutilization. We developed an electronic health record (EHR) embedded, quality improvement (QI) oriented clinical trial to determine whether standardized management of HFNC weaning guided by clinical decision support (CDS) results in a reduction in the duration of HFNC compared to usual care for children with bronchiolitis. METHODS: The design and summary of the statistical analysis plan for the REspiratory SupporT for Efficient and cost-Effective Care (REST EEC; "rest easy") trial are presented. The investigators hypothesize that CDS-coupled, standardized HFNC weaning will reduce the duration of HFNC, the trial's primary endpoint, for children with bronchiolitis compared to usual care. Data supporting trial design and eventual analyses are collected from the EHR and other real world data sources using existing informatics infrastructure and QI data sources. The trial workflow, including randomization and deployment of the intervention, is embedded within the EHR of a large children's hospital using existing vendor features. Trial simulations indicate that by assuming a true hazard ratio effect size of 1.27, equivalent to a 6-h reduction in the median duration of HFNC, and enrolling a maximum of 350 children, there will be a > 0.75 probability of declaring superiority (interim analysis posterior probability of intervention effect > 0.99 or final analysis posterior probability of intervention effect > 0.9) and a > 0.85 probability of declaring superiority or the CDS intervention showing promise (final analysis posterior probability of intervention effect > 0.8). Iterative plan-do-study-act cycles are used to monitor the trial and provide targeted education to the workforce. DISCUSSION: Through incorporation of the trial into usual care workflows, relying on QI tools and resources to support trial conduct, and relying on Bayesian inference to determine whether the intervention is superior to usual care, REST EEC is a learning health system intervention that blends health system operations with active evidence generation to optimize the use of HFNC and associated patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05909566. Registered on June 18, 2023.

Seasonality of the incidence of bronchiolitis in infants - Brazil, 2016-2022: An interrupted time-series analysis.

OBJECTIVE: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. METHODS: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. RESULTS: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. CONCLUSIONS: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.

[Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children].

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Potential impact of nirsevimab and bivalent maternal vaccine against RSV bronchiolitis in infants: A population-based modelling study.

BACKGROUND: A new monoclonal antibody (nirsevimab; Beyfortus®) and a bivalent prefusion RSV vaccine (Abrysvo®) for maternal immunization have been approved recently. This is a modelling study to estimate the potential impact of different immunization programs with these products on RSV-bronchiolitis. METHODS: Population-based real-world data from primary care and hospitalizations were considered. RSV bronchiolitis dynamics in absence of these immunization scenarios were explained by a multivariate age-structured Bayesian model. Then, the potential impact was simulated under different assumptions including the most recent clinical trial data. Differences in endpoints, populations, and timeframes between trials make the two products' efficacy difficult to compare. RESULTS: A seasonal with catch-up program, assuming a constant effectiveness of 79.5 % during the first 5 months followed by a linear decay to 0 by month 10 with nirsevimab, would prevent between 5121 and 8846 RSV bronchiolitis per 100,000 infants-years. Assuming 77.3 % effectiveness with the same decay, between 976 and 1686 RSV-hospitalizations per 100,000 infants-years could be prevented depending on the uptake. A year-round maternal immunization program, with 51 % of effectiveness during the first 6 months followed by a linear decay to 0 by month 10 would prevent between 3246 and 5606 RSV bronchiolitis cases per 100,000 infants-years. Assuming 56.9 % effectiveness with the same decay, between 713 and 1231 RSV-hospitalizations per 100,000 infants-years could be prevented. CONCLUSIONS: Our results suggest that each strategy would effectively reduce RSV-bronchiolitis.

Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report.

BACKGROUND: Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature. CASE PRESENTATION: A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections. CONCLUSIONS: To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.

Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021-2022 Bronchiolitis Season in England, Scotland, and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637-29 486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Prevalence of and Risks for Bacterial Infections in Hospitalized Children With Bronchiolitis.

BACKGROUND AND OBJECTIVES: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. METHODS: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. RESULTS: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). CONCLUSIONS: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.

Impact of the COVID-19 Pandemic on Low-Value Testing and Treatment of Bronchiolitis.

BACKGROUND: Viral testing and treatments such as systemic steroids and inhaled corticosteroids are low-value care for routine bronchiolitis. We sought to determine the impact of the COVID-19 pandemic on low-value care in young children with bronchiolitis. METHODS: This was a retrospective, cross-sectional study using the Pediatric Health Information Systems database. We included children <2 years seen in a pediatric emergency department for bronchiolitis. We selected a priori 3 study periods: September 2018 to February 2020 (prepandemic), March 2020 to August 2022 (early pandemic), and September 2022 to January 2023 (late pandemic). Low-value care included respiratory syncytial virus testing, chest radiography, albuterol, or corticosteroids and was compared across the 3 time periods. RESULTS: At least 1 element of low-value care was provided in 45%, 47%, and 44% of encounters in the prepandemic, early pandemic, and late pandemic periods, respectively. There was little variation in the use of albuterol and chest radiography across time periods and a slight increase in systemic corticosteroid use from prepandemic to early and late pandemic groups. Viral testing increased from 36% prepandemic to 65% early pandemic and 67% late pandemic, which appeared to be driven by SARS-CoV-2 testing and combination viral testing. CONCLUSIONS: There was no clinically significant change in low-value care for bronchiolitis during the pandemic. Because of SARS-CoV-2 testing, however, overall frequency of viral testing increased dramatically over time. This marked increase in overall viral testing should be taken into consideration for future quality improvement efforts.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Effectiveness of nirsevimab immunoprophylaxis against respiratory syncytial virus-related outcomes in hospital and primary care settings: a retrospective cohort study in infants in Catalonia (Spain).

BACKGROUND: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab's effectiveness across primary and hospital care outcomes. METHODS: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs. RESULTS: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection. CONCLUSION: We demonstrated nirsevimab's effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns.

A two-tiered high-flow nasal cannula approach does not increase intensive care utilization and hospital length of stay in bronchiolitis.

While concerns about high-flow nasal cannula oxygen (HFNC) overuse and associated increased use of hospital resources are rapidly spreading, a two-tiered approach in its use is recommended by recent bronchiolitis guidelines. However, data on its effects in practice have not been reported. We aimed to analyze the trends in use of HFNC, hospitalizations, length of stay (LOS), and intensive care unit (ICU) admissions for bronchiolitis in a tertiary care center using a two-tiered HFNC approach since its introduction in practice. We retrospectively included data of children < 12 months of age who presented to the Paediatric Emergency Department (PED) and were hospitalized for bronchiolitis at our institution in the epidemic season between October 1st and April 30th during the years 2012-2023 and compared the clinical data across the years. Of the 687 hospitalized children included, 79.9% required oxygen supplementation. Use of HFNC significantly increased since its implementation (from 25% in 2012-2013 to over 60% since 2019-2020, p < 0.0001) and was most frequently administered as rescue treatment (in 57.5% of patients). There was no increased trend in ICU admissions (between 1.5% and 10.0% of hospitalizations across seasons, p = 0.40), while LOS, after increasing between 2013 and 2016 (medians between 4.0 and 5.4 days), remained stable thereafter (medians between 3.8 and 4.3 days). CONCLUSIONS: The use of HFNC according to a two-tiered approach does not appear to be associated with an increase in ICU utilization or LOS. WHAT IS KNOWN: • Bronchiolitis is one of the most common reasons for hospitalization in infants. • Use high-flow nasal canulae oxygen (HFNC) has rapidly spread outside the intensive care unit (ICU) to treat infants with bronchiolitis, although increasing evidence has dampened the initial enthusiasm about their effectiveness. • Concerns nowadays are rising about HFNC overuse and associated increased use of hospital resources, including escalation of care to ICU. WHAT IS NEW: • A more selective use of HFNC according to a "two-tiered approach", intended as a second-line rescue treatment in non-severely ill children who fail standard oxygen therapy, is not associated with increased ICU and length of hospital stay.

Parental knowledge on the respiratory syncytial virus before the nirsevimab immunization program: Attitudes toward immunization in an autonomous community of Spain.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.

Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study.

OBJECTIVE: To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit. STUDY DESIGN: In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV-). RESULTS: Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV- children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life. CONCLUSION: RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV- children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.