Real-world effectiveness of nirsevimab immunisation against bronchiolitis in infants: a case-control study in Paris, France.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Nirsevimab, an RSV-neutralising monoclonal antibody, was approved for use in the EU in 2022, and a national immunisation campaign began in France in September, 2023. We aimed to assess the effectiveness of nirsevimab in reducing paediatric emergency department visits (and subsequent hospitalisations) for all-cause bronchiolitis and RSV-associated bronchiolitis. METHODS: In this case-control study in a paediatric emergency department in Paris, France, we included all infants aged 12 months or younger who attended the department between Oct 14, 2023, and Feb 29, 2024, and whose nirsevimab status was known. Infants were classed as cases if they had all-cause bronchiolitis; all other infants were classed as controls. The primary outcome was the effectiveness of nirsevimab against paediatric emergency department visits for all-cause bronchiolitis during the 2023-24 RSV season. Secondary outcomes were paediatric emergency department visits for RSV-associated bronchiolitis; hospitalisations for all-cause bronchiolitis, RSV-associated bronchiolitis, and severe RSV-associated bronchiolitis requiring supplemental oxygen or feeding by nasogastric tube; and severe RSV-associated bronchiolitis requiring admission to the paediatric intensive care unit. Effectiveness estimates were adjusted for age, week of paediatric emergency department visit, and sex. FINDINGS: Our study included 2786 infants, 864 with all-cause bronchiolitis (cases) and 1922 without bronchiolitis (controls). 178 (21%) of the 864 cases had received nirsevimab, and 305 (35%) cases were hospitalised for all-cause bronchiolitis. 200 (72%) of the 277 cases tested for RSV were positive, of whom 22 (11%) had received nirsevimab. 701 (36%) of 1922 infants in the control group had received nirsevimab. The effectiveness of nirsevimab against paediatric emergency department visits for all-cause bronchiolitis was 47% (95% CI 33-58). Nirsevimab effectiveness was 83% (71-90) against paediatric emergency department visits for RSV-associated bronchiolitis, 59% (42-71) against hospitalisations for all-cause bronchiolitis, 83% (72-90) against hospitalisations for RSV-associated bronchiolitis (91% [78-96] against those necessitating supplement oxygen and 88% [74-95] against those necessitating feeding via a nasogastric tube). Nirsevimab did not significantly reduce admissions to the paediatric intensive care unit (67% [95% CI -100 to 95]). INTERPRETATION: During the first French national immunisation campaign, a single dose of nirsevimab effectively reduced paediatric emergency department visits (both all-cause visits and visits related to RSV-associated bronchiolitis) and subsequent hospitalisations. FUNDING: None.

Effect of nirsevimab on hospitalisations for respiratory syncytial virus bronchiolitis in France, 2023-24: a modelling study.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalisations and deaths among infants worldwide. France was one of the first countries to implement a national programme (beginning on Sept 15, 2023) for administration of nirsevimab, a single-dose long-acting monoclonal antibody treatment, to infants born on or after Feb 6, 2023, to prevent lower respiratory tract infection caused by RSV. We aimed to estimate the effectiveness of nirsevimab and the number of hospitalisations averted in children younger than 24 months in real-world settings. METHODS: In this modelling study, we developed an age-structured deterministic model characterising RSV transmission as well as plausible scenarios for the administration of nirsevimab doses based on maternity ward and community pharmacy supply data. We retrospectively estimated nirsevimab effectiveness in infants younger than 24 months during the 2023-24 RSV season in France (excluding overseas territories) and the number of averted hospitalisations for RSV bronchiolitis occurring after emergency department visits, by calibrating the model to hospital and virological surveillance data from Aug 21, 2017, to Feb 4, 2024, alongside serological data from a previous cross-sectional study. To assess the robustness of our estimates, we conducted sensitivity analyses in which we modified our assumptions about the number of doses administered, the reconstruction of the number of RSV-associated hospitalisations for bronchiolitis, the duration of maternal and post-infection immunity to RSV, and the number of contacts in children aged 0-2 months. FINDINGS: We estimated that nirsevimab administration prevented 5800 (95% credible interval 3700-7800) RSV-associated hospitalisations for bronchiolitis after emergency department visits among children younger than 24 months, including 4200 (2900-5600) hospitalisations among those aged 0-2 months, between Sept 15, 2023 (the date nirsevimab was introduced), and Feb 4, 2024-a 23% (16-30) reduction in the total number of hospitalisations and a 35% (25-44) reduction in the 0-2 months age group, compared with the scenario without administration. In our baseline scenario, in which we estimated that 215 000 doses of nirsevimab were administered by Jan 31, 2024, the estimated effectiveness against RSV-associated hospitalisations for bronchiolitis was 73% (61-84), corresponding to one hospitalisation averted for every 39 (26-54) doses administered. In sensitivity analyses, nirsevimab remained effective against RSV-associated hospitalisations for bronchiolitis after emergency department attendance. INTERPRETATION: Our findings show that nirsevimab administration campaigns could effectively reduce the RSV-related hospital burden of bronchiolitis in children younger than 24 months. FUNDING: European Commission, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and INCEPTION project.

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

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.

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.

Antibiotic Use in Korean Children Diagnosed With Acute Bronchiolitis: Analysis of the National Health Insurance Reimbursement Data.

BACKGROUND: Acute bronchiolitis, the most common lower respiratory tract infection in infants, is mostly caused by respiratory viruses. However, antibiotics are prescribed to about 25% of children with acute bronchiolitis. This inappropriate use of antibiotics for viral infections induces antibiotic resistance. This study aimed to determine the antibiotic prescription rate and the factors associated with antibiotic use in children with acute bronchiolitis in Korea, where antibiotic use and resistance rates are high. METHODS: Healthcare data of children aged < 24 months who were diagnosed with acute bronchiolitis between 2016 and 2019 were acquired from the National Health Insurance system reimbursement claims data. Antibiotic prescription rates and associated factors were evaluated. RESULTS: A total of 3,638,424 visits were analyzed. The antibiotic prescription rate was 51.8%, which decreased over time (P < 0.001). In the multivariate analysis, toddlers (vs. infants), non-capital areas (vs. capital areas), primary clinics and non-tertiary hospitals (vs. tertiary hospitals), inpatients (vs. outpatients), and non-pediatricians (vs. pediatricians) showed a significant association with antibiotic prescription (P < 0.001). Fourteen cities and provinces in the non-capital area exhibited a wide range of antibiotic prescription rates ranging from 41.2% to 65.4%, and five (35.7%) of them showed lower antibiotic prescription rates than that of the capital area. CONCLUSION: In Korea, the high antibiotic prescription rates for acute bronchiolitis varied by patient age, region, medical facility type, clinical setting, and physician specialty. These factors should be considered when establishing strategies to promote appropriate antibiotic use.

Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study.

We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons.  This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form.  Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy. CONCLUSIONS: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world. WHAT IS KNOWN: • Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world. WHAT IS NEW: • There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.

Intravenous Magnesium Sulfate for Acute Bronchiolitis: Evaluation of the Effect on Clinical Course and Outcomes.

The aim of the present study was to assess the efficacy of intravenous (IV) magnesium sulfate (MgSO4) for children with bronchiolitis. A retrospective cohort study was performed at a pediatric emergency department. Aged between 1 and 24 months, children with moderate/severe bronchiolitis according to the Modified Respiratory Distress Assessment Instrument (mRDAI) score were included. Patients who received 40 mg/kg/dose of IV MgSO4 (group 1, n: 74) or not (group 2, n: 33) were compared. Respiratory rate and mRDAI score significantly decreased at the second hour of MgSO4 treatment and the decrease was observed for 4th, 8th, and 12th hours, compared with group 2. Patients in group 2 had a higher rate of requirement and an earlier start high-flow nasal cannula oxygen therapy and a longer hospital stay than group 1. Intravenous MgSO4 provided significant improvement on clinical severity, need for respiratory support, length of hospital stay, and outcomes.

Inhaled nitric oxide in acute bronchiolitis: A systematic review and meta-analysis.

OBJECTIVE: Until date there is lack of effective therapies in acute bronchiolitis in infants. The aim was to analyze inhaled nitric oxide efficacy in acute bronchiolitis. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: Pediatric specialized healthcare. PATIENTS: All infants (age less than 2 years) having acute bronchiolitis, which requires emergency room visit or hospitalization. INTERVENTION: Inhaled nitric oxide. MAIN OUTCOME MEASURES: Need for intensive care unit admission. Secondary outcomes were length of hospital stay and adverse events. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) calculated by random-effects DerSimonian and Laird inverse variance method. Peto Odds ratios were used for rare outcomes. Evidence certainty assessed according to GRADE. RESULTS: 186 studies were screened and three included for analysis. Two had low risk of bias and one had some concerns. Three studies (166 infants) analyzed length of hospital stay and the duration was -11.3 h (CI: -26.8 to +4.2 h) shorter in the nitric oxide group. Evidence certainty was ranked as low. Overall adverse event rates were similar (3 studies, 166 infants, RR: 0.94, CI: 0.70-1.26), but treatment related harms were more common in nitric oxide group (2 studies, 98 infants, OR: 3.86, CI: 1.04-14.40). Evidence certainty in both was rated as low. CONCLUSIONS: Low certainty evidence suggests that inhaled nitric oxide does not reduce length of hospital stay but may have higher rate of treatment associated harms. Future studies with larger sample sizes are needed to better estimate both the efficacy and adverse events.

Changes in Bronchiolitis Characteristics During the COVID-19 Pandemic: A Description of Pediatric Emergency Department Visits in a Community Hospital, 2019-2021.

A retrospective, cross-sectional study of children with bronchiolitis aged 1 to 24 months during an ED visit between 2019 and 2021 was performed. Chi-square or Kruskal-Wallis was used to compare groups. The gamma coefficient was used to measure the association of variables through time. Bronchiolitis cases decreased by 75% from 2019 to 2020 and rose back to prepandemic levels by 2021. Radiographs (gamma -0.443), steroids (gamma -0.298), and bronchodilators (gamma -0.414) decreased during the study period (P < .001). Laboratory studies (gamma 0.032), viral testing (gamma 0.097), antibiotic use (gamma -0.069), and respiratory support (gamma 0.166) were unchanged. The decrease in steroids and bronchodilators was related to a clinical pathway that discouraged their use. Respiratory support remained unchanged. The COVID-19 pandemic (2019-2021) seems to have had little effect on the severity or resource utilization associated with bronchiolitis but may have unraveled a potential bronchiolitis phenotype that may have been more prominent during the pandemic.

Nebulised 3% hypertonic saline versus 0.9% saline for treating patients hospitalised with acute bronchiolitis: protocol for a randomised, double-blind, multicentre trial.

INTRODUCTION: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis. METHODS AND ANALYSIS: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation. ETHICS AND DISSEMINATION: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06069336).

Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).

INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease. METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions. RESULTS: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis. CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.

Management Practices for Standard-Risk and High-Risk Patients With Bronchiolitis.

OBJECTIVE: Management guidelines for bronchiolitis advocate for supportive care and exclude those with high-risk conditions. We aim to describe and compare the management of standard-risk and high-risk patients with bronchiolitis. METHODS: This retrospective study examined patients <2 years of age admitted to the general pediatric ward with an International Classification of Diseases, 10th Revision discharge diagnosis code of bronchiolitis or viral syndrome with evidence of lower respiratory tract involvement. Patients were defined as either standard- or high-risk on the basis of previously published criteria. The frequencies of diagnostic and therapeutic interventions were compared. RESULTS: We included 265 patients in this study (122 standard-risk [46.0%], 143 high-risk [54.0%]). Increased bronchodilator use was observed in the standard-risk group (any albuterol dosing, standard-risk 65.6%, high-risk 44.1%, P = .003). Increased steroid use was observed in the standard-risk group (any steroid dosing, standard-risk 19.7%, high-risk 14.7%, P = .018). Multiple logistic regression revealed >3 doses of albuterol, hypertonic saline, and chest physiotherapy use to be associated with rapid response team activation (odds ratio [OR] >3 doses albuterol: 8.36 [95% confidence interval (CI): 1.99-35.10], P = .048; OR >3 doses hypertonic saline: 13.94 [95% CI: 4.32-44.92], P = .001); OR percussion and postural drainage: 5.06 [95% CI: 1.88-13.63], P = .017). CONCLUSIONS: A varied approach to the management of bronchiolitis in both standard-risk and high-risk children occurred institutionally. Bronchodilators and steroids continue to be used frequently despite practice recommendations and regardless of risk status. More research is needed on management strategies in patients at high-risk for severe disease.