Respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants.1 A 2022 birth cohort study estimated that 14% of healthy children born at term had an RSV infection ...that was medically attended and 1·8% were admitted to hospital for RSV in their first year of life.2 A 2015 study found approximately 10% of RSV infections were asymptomatic in children younger than 1 year, suggesting that total RSV incidence is high.3 Recurrent wheeze and childhood asthma have been associated with RSV bronchiolitis.4,5 Clinical trials that investigated if monoclonal antibodies against RSV decreased the risk of childhood asthma have been inconsistent so far.6–8 It remains unclear to what extent RSV increases the risk of childhood asthma, and to what extent shared genetic predisposition and environmental risk factors cause a subset of children to be at higher risk of severe RSV and childhood asthma. ...long follow-up requires substantial resources, and it is unclear if companies would be interested in this commitment without public support. LJB has regular interaction with pharmaceutical and other industrial partners and has not received personal fees or other personal benefits; the University Medical Center Utrecht has received funding for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics; major funding for the RSV GOLD study from the Bill & Melinda Gates Foundation; major funding as part of the public–private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi; major funding by Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer; and funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, Astrazeneca, MSD, Sanofi, Genzyme, and Janssen.
A relationship between hospitalization for respiratory syncytial virus (RSV) bronchiolitis and asthma development has been suggested in case-control studies.
The aim of this study was to assess the ...risk of current wheeze, asthma, and lung function at school age in infants previously hospitalized for RSV bronchiolitis compared to non-hospitalized children.
For this study, data from a prospective birth cohort of unselected, term-born infants (n = 553), of whom 4 (0.7%) were hospitalized for RSV bronchiolitis, and a prospective patient cohort of 155 term infants hospitalized for RSV bronchiolitis were used. Respiratory outcomes at age 6 in children hospitalized for RSV bronchiolitis were compared to non-hospitalized children.
The risk of current wheeze was higher in hospitalized patients (n = 159) compared to non-hospitalized children (n = 549) (adjusted odds ratio (OR) 3.2 (95% CI 1.2-8.1). Similarly, the risk of current asthma, defined as a doctor's diagnosis of asthma plus current symptoms or medication use, was higher in hospitalized patients (adjusted OR 3.1 (95% CI 1.3-7.5). Compared to non-hospitalized children, RSV bronchiolitis hospitalization was associated with lower lung function (mean difference FEV1% predicted -6.8 l (95% CI (-10.2 to -3.4).
This is the first study showing that hospitalization for RSV bronchiolitis during infancy is associated with increased risk of wheezing, current asthma, and impaired lung function as compared to an unselected birth cohort at age 6.
IMPORTANCE: Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in young children. RSV largely disappeared in 2020 owing to precautions taken because of the COVID-19 pandemic. ...Estimating the timing and intensity of the reemergence of RSV and the age groups affected is crucial for planning for the administration of prophylactic antibodies and anticipating hospital capacity. OBJECTIVE: To examine the association of different factors, including mitigation strategies, duration of maternal-derived immunity, and importation of external infections, with the dynamics of reemergent RSV epidemics. DESIGN, SETTING, AND PARTICIPANTS: This simulation modeling study used mathematical models to reproduce the annual epidemics of RSV before the COVID-19 pandemic in New York and California. These models were modified to project the trajectory of RSV epidemics from 2020 to 2025 under different scenarios with varying stringency of mitigation measures for SARS-CoV-2. Simulations also evaluated factors likely to affect the reemergence of RSV epidemics, including introduction of the virus from out-of-state sources and decreased transplacentally acquired immunity in infants. Models using parameters fitted to similar inpatient data sets from Colorado and Florida were used to illustrate these associations in populations with biennial RSV epidemics and year-round RSV circulation, respectively. Statistical analysis was performed from February to October 2021. MAIN OUTCOMES AND MEASURES: The primary outcome of this study was defined as the estimated number of RSV hospitalizations each month in the entire population. Secondary outcomes included the age distribution of hospitalizations among children less than 5 years of age, incidence of any RSV infection, and incidence of RSV lower respiratory tract infection. RESULTS: Among a simulated population of 19.45 million people, virus introduction from external sources was associated with the emergence of the spring and summer epidemic in 2021. There was a tradeoff between the intensity of the spring and summer epidemic in 2021 and the intensity of the epidemic in the subsequent winter. Among children 1 year of age, the estimated incidence of RSV hospitalizations was 707 per 100 000 children per year in the 2021 and 2022 RSV season, compared with 355 per 100 000 children per year in a typical RSV season. CONCLUSIONS AND RELEVANCE: This simulation modeling study found that virus introduction from external sources was associated with the spring and summer epidemics in 2021. These findings suggest that pediatric departments should be alert to large RSV outbreaks in the coming seasons, the intensity of which could depend on the size of the spring and summer epidemic in that location. Enhanced surveillance is recommended for both prophylaxis administration and hospital capacity management.
Summary Background A physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related ...apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers. Methods In this prospective, double-blind, international, multicentre study, we recruited children aged 2–60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome. Findings Between Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8–93·1), a specificity of 91·1% (87·9–93·6), a positive predictive value of 60·5% (49·9–70·1), and a negative predictive value of 97·8% (95·6–98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5–94·7), specificity 93·0% (89·6–95·3), positive predictive value 62·1% (49·2–73·4), and negative predictive value 98·3% (96·1–99·3). Interpretation This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children. Funding MeMed Diagnostics.
Dr. Karron and colleagues have previously made several attempts to develop a live-attenuated vaccine against respiratory syncytial virus (RSV) to protect children against one of the most common ...severe diseases during childhood. They have performed as many as seven phase I trials with different intranasal vaccine candidates. Here, they describe a pooled analysis of these early stage trials among 241 children aged 6-24 months. The authors took advantage of the postvaccination surveillance of acute respiratory infection used to monitor the occurrence of enhanced RSV disease in vaccine recipients to assess the overall vaccine efficacy and key immunogenicity endpoints. While analyzing these trials, they distinguished these vaccines into more and less immunogenic vaccines based on induced serum-neutralizing antibodies. Four vaccines that induced at least a fourfold increase in neutralization of the vaccine recipients were referred to as "more promising" vaccines, in opposition to "less promising" ones. Pooling data from trials with these more immunogenic vaccines, vaccine efficacy against RSV-associated medically attended respiratory infection was 67%, which suggests these vaccines might indeed hold a promise for RSV-naive children.
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