Respiratory Syncytial Virus Bronchiolitis Research Articles

Introduction of nirsevimab in Catalonia, Spain: description of the incidence of bronchiolitis and respiratory syncytial virus in the 2023/2024 season.

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0-6months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11m-old with respect to 12-35m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11m-old and 12-35m-old with respect to the > 35m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11m-old RR (95% CI) of RSV infection incidence for > 35m-old was 1.7 (1.5-2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6-9.9), 8.8 (6.9-11.3), and 7.1 (5.7-8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11m-old group compared to the 12-35m-old, the pre-pandemic (2014/2015-2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2-9.6) and 6.0 (5.7-6.2), respectively, significantly higher than the RR of 3.6 (3.4-3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11m-old compared to > 35m-old has been reduced by 75.6% (73.4-77.5) in last season, and the risk for all-causes bronchiolitis for 12-35m-old by 61.9% (60.9-62.9) from the pre-pandemic period and by 39.8% (39.3-40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using. primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%.

Efectividad de nirsevimab en la prevención de los ingresos por bronquiolitis por virus respiratorio sincitial en lactantes

Introduction. Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. This season, a long half-life monoclonal antibody (Nirsevimab) is available to prevent this disease for all infants born from 1 April-30 September to 2023 and all those born during RSV season (October2023- March 2024). The aim of this study was to evaluate the impact of the implementation of this antibody on RSV admissions in a tertiary hospital. Material and methods. Observational, retrospective and analytical study. All patients &lt;6 months in October admitted for bronchiolitis at 2 time points were included: T1 or Pre-nirsevimab time: 1 September 2015-30 September 2023 and T2 or Nirsevimab time: 1 October-31 December 2023. Total admissions due to any cause of infants &lt;6 months in the same period were used as the reference population. To assess the impact of the implementation of nirsevimab, we calculated the reduction in the percentage of admissions due to RSV with respect to total admissions in both periods, and also in the 2023-2024 season we calculated the double negative test to calculate the effectiveness of the intervention (1-Odds ratio) x 100. Results. In infants under 6 months of age, we found significant differences in the number of admissions for RSV bronchiolitis between the last season and the previous 7 seasons [574/1195 (48%) vs 6/138 (4.3%); p&lt;0.01, RPI: 91%). In the 2023/2024 season, the effectiveness of nirsevimab in preventing admission for RSV bronchiolitis in children under 6 months of age was 85% (CI 95%: 32-97%). Conclusions. The implementation of nirsevimab has had an important impact on the number of hospital admissions for RSV bronchiolitis. There were no differences in the severity of bronchiolitis

Management of RSV Bronchiolitis in Outpatient Setting

AbstractSeasonal respiratory syncytial virus (RSV) lower respiratory infections (RSV-LRI) and bronchiolitis in children remain a high burden to medical facilities. Studies evaluating the practical approach in outpatient settings are scarce. We conducted a survey to provide an insight into management in pediatric offices in Germany. Invitations for participation in an online survey were sent to 623 providers of pediatric primary care via email. Recipients were randomly chosen from national databanks based on zip codes. The response rate was 16,2%, n=92 (14,7%) questionnaires were fully answered and analyzed. 93,5% (n=86) are board certified pediatricians. In outpatient setting, every second patient with suspected or confirmed RSV-LRI is presented three times or more. 40,7% of our participants refer less than 10% of all patients to hospital, 83,7% refer less than one third (&lt;30%). 33,7% of all participants never perform virological testing in suspected cases of RSV-LRI. More than 50% of all participants prescribe bronchodilators, hypertonic saline inhalation is prescribed by 17,4%. Antibiotics are prescribed in less than 10% of all cases of RSV-LRI. About 3/4 ask for a clearer, more conclusive guideline regarding prophylaxis. The diagnostic approach varies significantly. Although not recommended in international guidelines, bronchodilators are still frequently used. Considering emerging options for passive immunization, broader inclusion criteria into immunization regimes are requested by the participants. More conclusive guidelines and recommendations could further improve the management of outpatient RSV-LRI in children.

Paid Family Leave and Prevention of Acute Respiratory Infections in Young Infants

Acute respiratory tract infections are the leading cause of emergency department visits and hospitalizations in US children, with highest risks in the first 2 months after birth. Out-of-home childcare settings increase the spread of respiratory tract infections. The study team hypothesized that access to state-paid family leave could reduce acute care encounters (hospital admissions or emergency department visits) for respiratory tract infections in young infants by reducing out-of-home childcare transmissions. To determine if the 2018 introduction of paid family leave in New York state reduced acute care encounters for respiratory tract infections in infants 8 weeks or younger. This population-based study of acute care encounters took place in New York state and New England control states (Maine, Massachusetts, New Hampshire, Vermont) from October 2015 through February 2020. Participants included infants aged 8 weeks or younger. Controlled time series analysis using Poisson regression was used to estimate the impact of paid family leave on acute care encounters for respiratory tract infections, comparing observed counts during respiratory virus season (October through March) with those predicted in the absence of the policy. Acute care encounters for respiratory tract infections in 1-year-olds (who would not be expected to benefit as directly from the policy) were modeled as a placebo test. New York State Paid Family Leave policy, introduced on January 1, 2018, providing 8 weeks of paid leave for eligible parents. Emergency department visits or hospitalizations with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD) codes for upper or lower respiratory tract infections or associated symptoms (ie, fever, cough), excluding newborn hospitalizations. The secondary outcome was acute care encounters for respiratory syncytial virus (RSV) bronchiolitis. There were 52 943 acute care encounters for respiratory infection among infants 8 weeks or younger. There were 15 932 encounters that were hospitalizations (30%) and 33 304 of the encounters were paid for by Medicaid (63%). Encounters were 18% lower than predicted (relative percentage change = -17.9; 95% CI, -20.3 to -15.7) after the introduction of paid family leave. RSV encounters were 27.0% lower (95% CI, -30.9 to -23.5) than predicted. Similar reductions were not observed in 1-year-olds (relative percentage change = -1.5; 95% CI, -2.5 to -0.6). New York state's paid family leave policy was associated with reduced acute care encounters for respiratory tract infections in young infants. These findings may be useful for informing implementation of paid family leave federally and in the states that have not enacted paid family leave policies.

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

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. 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. 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. Our findings show that nirsevimab administration campaigns could effectively reduce the RSV-related hospital burden of bronchiolitis in children younger than 24 months. European Commission, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and INCEPTION project.

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.

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

BackgroundRespiratory 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,...

Epidemiology, Outcomes, and Trend Analysis of Hospitalized Infants With Respiratory Syncytial Virus (RSV) Bronchiolitis From 1997 to 2019.

Background Most children with respiratory syncytial virus (RSV) infection have a self-limiting course that can be managed with supportive care, and hospitalization is uncommon. The objectives of this study were to evaluate the epidemiology, outcomes, associated comorbidities, and temporal trends in the prevalence of infants one to 24 months of age who required hospitalization for RSV infection in the United States of America from 1997 to 2019. Methods In this retrospective cross-sectional study, we utilized the Kids' Inpatient Database (KID) to investigate the prevalence and outcomes of RSV bronchiolitis within a large cohort of discharged patients from 1997 to 2019. We included children one to 24 months of age admitted with a diagnosis of RSV bronchiolitis. Neonates were excluded from the analysis. A chi-square for linear trend was used to analyze trends in the prevalence of RSV bronchiolitis hospitalization, the presence of complex chronic conditions (CCC), congenital heart disease (CHD), the use of non-invasive and invasive mechanical ventilation (NIV and IMV), and hospital mortality. Results There were a total of 566,786 infants aged one to 24 months hospitalized with RSV infection out of a total of 9,309,597 discharges during the eight-year cohort, with a hospital prevalence of 60.9 per 1000 discharges and a hospital mortality rate of 0.09% (95% confidence interval (CI): 0.08%-0.1%). There was no trend in hospitalization rates of RSV infections per 100,000 U.S. population during the study period, with a decrease in hospital mortality trend. Children with RSV bronchiolitis were more likely to have government insurance and reside in zip codes with the lowest income quartile. There was a significant seasonal and regional variation in RSV-related hospitalizations. The presence of CCC was identified in 2.4% of the RSV group compared to 5.1% of non-RSV discharges (odds ratio (OR): 0.46, 95% CI: 0.45-0.47; p<0.001). The prevalence of RSV among all discharges has significantly increased over the study period, rising from 51.6 cases per 1000 discharges in 1997 to 180.1 cases per 1000 discharges in 2019 (p<0.001). The prevalence of CCC and CHD among RSV patients has also shown an upward trend, with CCC cases increasing from 1,411 in 1997 to 2,795 in 2019 and CHD cases rising from 1,795 to 3,622 during the same period. The use of invasive mechanical ventilation, non-invasive ventilation, and extracorporeal membrane oxygenation has consistently increased over time. Additionally, complications such as the need for cardiopulmonary resuscitation have demonstrated a similar increasing trend, although they have remained overall low. However, population-based hospitalization rates showed no significant trend. Conclusions The hospitalization rates at a population level in the United States for RSV infection in children aged one to 24 months remained steady from 1997 to 2019, while hospital mortality rates showed a declining trend. There is an increased proportion of comorbid conditions and increased resource utilization in children with RSV. These findings are important for monitoring the effectiveness of preventive strategies for severe RSV infections.

SARS-CoV-2 and RSV bronchiolitis outcomes

BackgroundSevere acute respiratory syndrome related coronavirus (SARS-CoV-2) bronchiolitis has arisen with the SARS-CoV-2 pandemic. There is a paucity of literature on SARS-CoV-2 bronchiolitis. ObjectiveThe purpose of our paper was to review and compare outcomes in bronchiolitis due to severe acute respiratory syndrome related coronavirus 2 (SARS- CoV-2) and Respiratory Syncytial Virus (RSV). We also performed a subgroup analysis of two disrupted RSV seasons during the pandemic. MethodsThis was a retrospective study from a US TriNetX database from March 1, 2020-January 1, 2023. Propensity matching was utilized for confounders. ResultsThere was a total of 3,592 patients (1,796 in each group) after propensity matching.There was an increased risk of oxygen saturation ≤95 % (RR=1.50 95 % CI 1.58–1.94, p = 0.002) and ICU admission (RR=1.44 95 % CI 1.06–1.94, p = 0.02) in those with SARS- CoV-2 but not for oxygen saturation ≤90 % (RR=1.03 95 %CI 0.75–1.42, p = 0.85) or intubation (RR=0.73 95 % CI 0.35–1.47, p = 0.37). There was a decreased risk of a patient with SARS- CoV-2 bronchiolitis being hospitalized (RR=0.65 95 % CI 0.57–0.74, p < 0.0001), respiratory rate ≥60 (RR=0.64 95 % CI 0.48–0.88, p < 0.001) or ≥70 (RR=0.64 95 % CI 0.43–0.96, p = 0.03) when compared to RSV bronchiolitis. Specifically examining SARS- CoV-2 versus RSV bronchiolitis during the delayed RSV seasons, during the first season both infections were not severe, but during the second RSV bronchiolitis season, patients infected with RSV had less risk of ICU admission compared to those infected with SARS- CoV-2. ConclusionSARS- CoV-2 bronchiolitis patients appeared to have more severe outcomes since the risk of ICU admission was higher for these patients. Also, during the second delayed RSV season, SARS- CoV-2 bronchiolitis was more severe than RSV bronchiolitis.

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

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. 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. 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. 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. 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.

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)

BackgroundIn 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...

Parent's perception of respiratory syncytial virus and subsequent wheezing burden: A multi-country cross-sectional survey.

Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We aimed to document the parents' perception of the link between RSV infection and subsequent wheezing, wheezing-related healthcare and family resources use, and its impact on family daily life. This cross-sectional online survey enrolled 1200 parents with at least one child ≤6y living in the United States, United Kingdom, Spain, and Italy. Children diagnosed with RSV bronchiolitis before age of 2 years were included in the RSV group, and those never diagnosed with RSV bronchiolitis in the Reference group. The odds of wheezing were 4.5-fold (95%CI 3.5-5.9) higher in the RSV than in the Reference group. The odds increased to 7.7-fold (95%CI 5.4-11.1) among children who were hospitalized, and 9-fold (95%CI 5.1-16.6) among those admitted to pediatric intensive care with RSV bronchiolitis. Similar trends were observed across all countries. In total, 57% of parents reported their child's wheezing to have moderate to severe impact on their emotional well-being, and 53% on their daily life activities and/or social life. 64% of parents reported moderate-severe impact of wheezing on child's quality of sleep and 49% and 46% reported a moderate-severe impact on their children's emotional well-being and physical activities. This survey suggests an association between RSV infection and subsequent wheezing in children across different countries. Wheezing, especially in association with RSV infection, was associated with increased healthcare utilization and costs, and significantly impacted parents' and children daily life.

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

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. 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. 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. 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.

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.

Viral load in hospitalized infants with respiratory syncytial virus bronchiolitis: a three-way comparative analysis.

Viral load measurement ofRespiratory syncytial virus (RSV) in acute bronchiolitis depends on specimen collection, viral load quantification, and transport media.The aim of this study wasto investigate viral load in three-way-comparative analyses; nasal swab versus nasal wash, quantitative real-time polymerase chain reaction (RT-PCR) versus cell tissue culture, and various transport media.A prospective cohort study of infants aged < 12 months, admitted to the Soroka Medical Center, due to acute bronchiolitis, was conducted. Two nasal swabs and two nasal wash samples (in UTM and VCM) were collected from each infant upon admission and after 48h. Samples were immediately stored at -80 °C and tested at Viroclinics DDL (Rotterdam, Netherlands). Quantitative RT-PCR and quantitative virus culture were performed using tissue culture infective dose (TCID50). Spearman's correlation coefficient test assessed the correlation between the different methods, viral load, and clinical severity score. One hundred samples were collected from 13 infants (mean age 5.7 ± 3.8 months, 46% males). Twelve patients were RSV-A positive, and one was RSV-B positive. A high correlation was found between transport media- UTM and VCM (0.92, P < 0.001) and between nasal swabs and nasal wash samples (0.62, P = 0.02). RSV signals were higher in nasal wash than in swabs. PCR signals were lower in the second collection compared to the first. No correlation was found between viral load and clinical severity. Conclusion: RSV viral load is comparable across nasal wash, nasal swabs, and various transport media. However, it did not correlate with clinical severity, probably due to the limited sample size. Broader analyses are warranted. What is Known: • Viral load measurement in Respiratory Syncytial Virus (RSV) bronchiolitis depends on specimen collection, viral load quantification, and transport media. • The COVID-19 pandemic underscored the paramount significance of proper specimen collection, notably through nasal swabs. What is New: • RSV viral load was investigated in three-way-comparative analyses. • RSV viral load correlated well across PCR and tissue culture, nasal wash and swabs, and various transport media.RSV viral load did not correlate with clinical severity.

Safety and Efficacy of Nirsevimab in a Universal Prevention Program of Respiratory Syncytial Virus Bronchiolitis in Newborns and Infants in the First Year of Life in the Valle d'Aosta Region, Italy, in the 2023-2024 Epidemic Season.

Respiratory syncytial virus (RSV) bronchiolitis remains a significant global health burden, particularly in newborns and infants during their first year of life. The quest for an effective preventive strategy against RSV has long been sought, and recent developments have shown promise in the form of nirsevimab, a monoclonal antibody specifically designed for RSV prophylaxis. Valle d'Aosta was the first Italian region to propose universal prophylaxis with nirsevimab for newborns and infants in their first epidemic season as early as 2023-2024. This study describes the effectiveness and safety of the universal prevention program of RSV bronchiolitis using the monoclonal antibody nirsevimab in children resident in Valle d'Aosta born during the 2023-2024 epidemic season. There were 556 neonates born from 1 May 2023 to 15 February 2024. The risk of hospitalization for RSV bronchiolitis in 2023-2024 was 3.2%, compared to 7% in the 2022-2023 epidemic season (p < 0.001). After the start of the prophylaxis campaign with nirsevimab, the risk of hospitalization was 8.3% in the sample of infants who did not adhere to the prophylaxis, while no child in the sample of those treated (p < 0.001) was hospitalized for bronchiolitis. Few mild transient side effects were reported. This study shows the efficacy and safety of universal prophylaxis with nirsevimab in neonates, making Valle d'Aosta the first Italian region to offer universal prophylaxis to newborns without risk factors for RSV complications. Future research could further explore its long-term impact and cost-effectiveness.

RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia.

Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animals models that recapitulate bronchiolitis and bronchopneumonia; both hallmark features of severe RSV infection of humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV resulting in a sustained virus replication. Here, we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV infected epithelial cells lining the airway and alveolar regions of human lung implants resulting in hallmark histological features of RSV bronchiolitis and bronchopneumonia including distal airway and alveolar lumens clogged with 1) sloughed and necrotic RSV-infected epithelial cells, 2) neutrophil-containing inflammatory infiltrates, and 3) MUC5B dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Together, our data show that RSV infection of human lung implants in vivo has appropriate cellular tropism and results in hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection.

Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID-19: Results From Four Health Systems, 2015-2023.

Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID-19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described. Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023. Prior to widespread circulation of SARS-CoV-2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID-19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era. Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.

Does weight influence the course of RSV bronchiolitis in hospitalized infants?

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease. Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study.

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit. A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001). This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.