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.

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.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

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.

Identifying the impact of non-pharmaceutical interventions on RSV transmission in a single-centre observational study.

During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory syncytial virus (RSV), the predominant cause of bronchiolitis. As NPIs were eased, it was speculated that RSV transmission would return with an increase in the severity of bronchiolitis. In a large tertiary hospital, a dramatic reduction in the incidence of bronchiolitis was seen during the COVID-19 pandemic. The easing of NPIs correlated with an increase in RSV transmission particularly in the community; however, there was no evidence of an increase in the severity of bronchiolitis.

Addressing global health disparities in the management of RSV infection in infants and children: Strategies for preventing bronchiolitis and post-bronchiolitis recurrent wheezing.

Background: The topic of equitable access to health care and its impact on exacerbating worldwide inequities in child health not only strikes at the heart of our health-care delivery systems but also deeply resonates with our collective social consciences. Nowhere is this better seen on a global scale than in the burden of illness caused by respiratory syncytial virus (RSV) infection, which extracts the most severe morbidity and mortality in infants and children in low- and middle-income countries (LMIC). This report addresses global health disparities that exist in the management of RSV infection in infants and children, and offers strategies for preventing bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Methods: A systematic literature review was conducted across the PubMed data bases of RSV infection and the socioeconomic impact of bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Results: The results of the present study address the many issues that deal with the question if prevention of RSV bronchiolitis can mitigate recurrent wheezing episodes and links RSV risks, downstream effects, prevention, malnutrition, and socioeconomic restraints of developing countries with a call for possible global action. Conclusion: The present study stresses the importance of considering the linkage between malnutrition and disease susceptibility because of the known relationships between undernutrition and greater vulnerability to infectious diseases, including RSV infection. These complex interactions between infectious disease and undernutrition also raise issues on the longer-term sequelae of postbronchiolitis recurrent wheezing. This prompts a discussion on whether industrialized countries should prioritize the provision of newly developed monoclonal antibodies and RSV vaccines to LMICs or whether vital nutritional needs should be a first focus. The resolution of these issues will require research and greater international discourse.

Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial.

BACKGROUND: Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects. METHODS: BREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child's sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home. DISCUSSION: We propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization. TRIAL REGISTRATION: NCT05615870. Registered on November 14, 2022.

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.

Hospitalization for bronchiolitis in children aged ≤ 1year, Southern Italy, year 2021: need for new preventive strategies?

BACKGROUND: Bronchiolitis is a major cause of hospitalization in infants, particularly in the first six months of life, with approximately 60-80% of admissions due to respiratory syncytial virus (RSV) infection. Currently, no prophylactic options are available for healthy infants. The present study aimed at describing the demographic, clinical, and epidemiological characteristics of infants hospitalized for bronchiolitis in the Apulia region of Italy in 2021. METHODS: From January to December 2021, data on children aged 0-12 months admitted for bronchiolitis in nine neonatal or pediatric units covering 61% of pediatric beds of hospitals in the Apulia region of Italy were analyzed. Demographic data, comorbidities, need for oxygen support, length of hospital stay, palivizumab administration, and outcomes were collected. For the purpose of the analysis, patients were divided into those aged 0-3 months and > 3 months. A multivariate logistic regression model was used to explore associations between the need for oxygen support and sex, age, comorbidities, history of prematurity, length of hospital stay, and palivizumab administration. RESULTS: This study included 349 children aged 0-12 months admitted for bronchiolitis, with a peak of hospitalization in November (7.4 cases/1,000 children). Of these patients, 70.5% were RSV positive, 80.2% were aged 0-3 months, and 73.1% required oxygen support. Moreover, 34.9% required observation in the sub-intensive care unit, and 12.9% in the intensive care unit. Of the infants who required intensive care, 96.9% were aged 0-3 months and 78.8% were born at term. Three patients required mechanical ventilation and one, who required Extra Corporeal Membrane Oxygenation, died. Children aged 0-3 months were more likely to show dyspnea, need oxygen support, and have a longer hospital stay. CONCLUSIONS: The present study showed that almost all of the children who required intensive care support were aged ≤ 3 months and most were born at term. Therefore, this age group remains the highest risk group for severe bronchiolitis. Preventive measures such as single-dose monoclonal antibody immunoprophylaxis, and maternal and childhood vaccination against RSV, may reduce the high public health burden of bronchiolitis.

[Design and reliability study of a parental knowledge, attitude, and practice questionnaire on prevention and management of acute bronchiolitis of children under two years of age].

BACKGROUND: Acute bronchiolitis is the most common cause of hospitalization in the first year of life. Primary prevention and supportive care are key. Here, we aimed to design and assess the psychometric properties of a parent-focused questionnaire on prevention and management of acute bronchiolitis at home in children under two years of age. METHODOLOGY: For the design of the questionnaire, we conducted a literature search on prevention strategies and risk factors for bronchiolitis. An expert committee evaluated the content of the new questionnaire using the Content Validity Index and estimated the internal consistency reliability with Cronbach's alpha. RESULTS: A 26-item questionnaire divided into four dimensions (Risk factors, Signs and symptoms, Prevention, Care and pharmacological support) was created. The normalized score fell in the range between -50 and +50; a positive score was interpreted as presence of good knowledge, attitudes, and habits. Each of the 26 items obtained a Content Validity Index score > 0.80 and the global score was 0.90. The global internal consistency was a = 0.77, with differences between individual scores of the different dimensions of the questionnaire. CONCLUSION: The Parental knowledge, attitude, and practice questionnaire on prevention and management of acute bronchiolitis at home obtained an excellent Content Validity Index score by the expert committee and an acceptable internal consistency. Our questionnaire may reinforce the weak knowledge areas regarding the measures to apply.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

RSV disease in infants and young children: Can we see a brighter future?

Respiratory syncytial virus (RSV) is a highly contagious seasonal virus and the leading cause of Lower Respiratory Tract Infections (LRTI), including pneumonia and bronchiolitis in children. RSV-related LRTI cause approximately 3 million hospitalizations and 120,000 deaths annually among children <5 years of age. The majority of the burden of RSV occurs in previously healthy infants. Only a monoclonal antibody (mAb) has been approved against RSV infections in a restricted group, leaving an urgent unmet need for a large number of children potentially benefiting from preventive measures. Approaches under development include maternal vaccines to protect newborns, extended half-life monoclonal antibodies to provide rapid long-lasting protection, and pediatric vaccines. RSV has been identified as a major global priority but a solution to tackle this unmet need for all children has yet to be implemented. New technologies represent the avenue for effectively addressing the leading-cause of hospitalization in children <1 years old.

Respiratory syncytial virus bronchiolitis in congenital diaphragmatic hernia: A systematic review of prevalence rates and palivizumab prophylaxis.

BACKGROUND: The seasonality of respiratory syncytial virus (RSV) epidemics have been disrupted during the COVID-19 pandemic, possibly because of lockdowns and social restrictions reducing viral transmission. Given uncertainties around the severity of upcoming RSV bronchiolitis epidemics, debate exists whether palivizumab (RSV prophylaxis) should be administered to infants with Congenital Diaphragmatic Hernia (CDH), who may be vulnerable due to lung hypoplasia and pulmonary hypertension. AIM: To evaluate (1) if CDH infants have higher risk of admission with RSV bronchiolitis than infants in the general population; (2) if palivizumab prophylaxis may reduce this risk. METHODS: We included all eligible studies examining the risk(s) of RSV-positive bronchiolitis requiring hospital admission in (1) CDH infants without palivizumab prophylaxis versus infants in the general population and (2) CDH infants with prophylaxis versus CDH infants without prophylaxis. The primary outcome evaluated was the risk of admission with RSV bronchiolitis. Data are reported descriptively and meta-analysed when appropriate. RESULTS: Three eligible retrospective cohort studies were identified: one study found CDH to be an independent risk factor for RSV hospitalisation (odds ratio, 3.30; 95% confidence interval [CI], 2.01-4.4); two studies compared RSV hospitalisation rates in CDH patients who had palivizumab versus those that did not. The pooled risk ratio was 1.11 (95% CI, 0.29-4.23; p = .88). Overall, the quality of evidence was considered poor and one study was industry funded. CONCLUSION: Whether CDH infants are at particular risk of severe bronchiolitis remains unclear. There is no evidence from this current systematic review that CDH infants should routinely receive palivizumab vaccination prophylaxis.

Bronchiolitis in children: diagnosis and management: Last updated 9 August 2021

This guideline covers diagnosing and managing bronchiolitis in babies and children. It aims to help healthcare professionals diagnose bronchiolitis and identify if babies and children should be cared for at home or in hospital. It describes treatments and interventions that can be used to help with the symptoms of bronchiolitis. In August 2021, we reviewed the evidence and updated the recommendations on oxygen saturation thresholds for referral to hospital, admission, management and timing of discharge.

Delayed Bronchiolitis Epidemic in French Primary Care Setting Driven by Respiratory Syncytial Virus: Preliminary Data from the Oursyn Study, March 2021.

We report early results from a prospective primary care bronchiolitis surveillance study in France in which a 10-week delayed epidemic was detected from February to March 2021. Among 225 children under 2 years with swab testing for a first bronchiolitis episode, 55% had a positive test for RSV, 0 for influenza, and 1 for severe acute respiratory syndrome coronavirus 2.

Early Impact of Social Distancing in Response to Coronavirus Disease 2019 on Hospitalizations for Acute Bronchiolitis in Infants in Brazil.

BACKGROUND: Interventions to tackle the coronavirus disease 2019 (COVID-19) pandemic may affect the burden of other respiratory diseases. Considering the repercussions of these unique social experiences to infant health, this study aims to assess the early impact of social distancing due to the COVID-19 pandemic in hospital admissions for acute bronchiolitis. METHODS: Data from hospitalizations of 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 2020. These data were also analyzed by macroregions of Brazil (North, Northeast, Southeast, South, and Midwest). To evaluate the effect of social distancing strategy on the incidence of acute bronchiolitis, the absolute and relative reductions were calculated by analyzing the yearly subsets of 2016 vs 2020, 2017 vs 2020, 2018 vs 2020, and 2019 vs 2020. RESULTS: There was a significant reduction in all comparisons, ranging from -78% (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}, .20-.24]) in 2016 vs 2020 to -85% (IRR, 0.15 [95% CI, .13-.16]) in 2019 vs 2020, for the data from Brazil. For analyses by macroregions, the reduction varied from -58% (IRR, 0.41 [95% CI, .37-.45]) in the Midwest in 2016 vs 2020 to -93% (IRR, 0.07 [95% CI, .06-.08]) in the South in 2019 vs 2020. CONCLUSIONS: There was a significant reduction in hospitalization for acute bronchiolitis in children <1 year old in Brazil, on the order of >70% for most analysis. Our data suggest an important impact of social distancing on reducing the transmission of viruses related to acute bronchiolitis. Such knowledge may guide strategies for prevention of viral spread.