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Background Respiratory syncytial virus (RSV) infection is gaining interest due to the recent development of vaccines but is still misdiagnosed in the elderly. The primary objective was to compare all-cause mortality at day 30. Secondary objectives were to compare clinical presentation and rates of consolidative pneumonia, hospitalization, and intensive care unit (ICU) admission. Methods A single-center retrospective study was conducted in a French university hospital during 7 epidemic seasons including 558 patients aged ≥75 years: 125 with RSV and 433 with influenza (median age, 84.8 years). Results Patients with RSV had more respiratory symptoms (wheezing, dyspnea) whereas patients with influenza had more general symptoms (fever, asthenia, myalgia). The following were higher in the RSV group: consolidative pneumonia (28.8% vs 17.2%, P =.004), hospitalization (83.2% vs 70%, P =.003), ICU admission (7.2% vs 3.0%, P =.034), and length of stay (median [IQR], 9 days [2–16] vs 5 days [0–12]; P =.002). Mortality rates at day 30 were comparable (9.6% vs 9.7%, P =.973). Conclusions This study included the largest cohort of patients infected with RSV aged >75 years documented in-depth thus far. RSV shares a comparable mortality rate with influenza but is associated with higher rates of consolidative pneumonia, hospitalization, ICU admissions, and extended hospital stays. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F2-F1 linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development. RSV and hMPV infections pose significant health risks in vulnerable populations. Here, the authors used a systematic approach to identify mutations critical for fusion protein metastability and rationally design uncleaved prefusion-closed trimers for RSV and hMPV F proteins that induce robust antibody responses in vivo. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections. Methods: In this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted. Results: Among 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection. Conclusions: During the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV. Methods: We collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed. Results: Our results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4–7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43–7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14–6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29–8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35–4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days. Conclusions: Our research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics. [ABSTRACT FROM AUTHOR]

Background While clinical risk factors for respiratory syncytial virus (RSV) bronchiolitis are well established, data on socioeconomic risk factors is lacking. We explored the association of parental education, income, and employment status on an infant's risk of hospitalization for RSV bronchiolitis. Methods This population-based retrospective case-control study covered all RSV-related hospital admissions of under 1-year-old children in Finland between 2004 and 2018. Controls were matched by month and year of birth, sex, province of residence, and family size. Registry data were linked using unique personal identity codes. Cases and controls were compared using adjusted odds ratios (aOR) calculated for socioeconomic outcomes including maternal and paternal education, household income, and parental employment. Results A total of 10 767 infants and 50 054 controls were included in the study. Lower parental education significantly raised the risk for RSV hospital admission in infants, the risk growing with decreasing education levels; aOR 1.03 (0.96-1.09) with post-secondary education, 1.12 (1.05-1.2) with secondary education, and 1.33 (1.2-1.47) with primary education. Combined parental income was not significant: aOR 0.97 (confidence interval [CI] 0.91-1.05), 1.02 (CI 0.95-1.1), 1 (CI 0.92-1.08), and 0.94 (CI 0.85-1.04), respectively with decreasing income level. Unemployment of both parents seemed to be a risk factor for the child's RSV hospital admission, aOR 1.24 (1.12-1.38). Conclusions Lower parental socioeconomic status may increase the risk of an infant's RSV hospitalization. Socioeconomic risk factors should be considered when designing RSV infection primary prevention strategies. [ABSTRACT FROM AUTHOR]

To determine if healthcare-associated (HA)-respiratory syncytial virus (RSV) is associated with worse outcomes, this multicenter cohort study studied 26 children with HA-RSV and 78 matched non-HA-RSV patients of whom 58% and 55%, respectively, had ≥2 comorbidities. Overall, 39% of HA-RSV versus 18% of non-HA-RSV patients required respiratory support escalation (adjusted odds ratio (aOR) 5.1, CI95 1.4, 19.1). [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) and influenza virus are major viral etiologies of pediatric lower respiratory tract infection, but comparative data on inpatient burden are lacking. Methods: Using a large‐scale health claims database in Japan, we identified patients under 5 years of age with a confirmed RSV or influenza diagnosis as an outpatient or inpatient between 2011 and 2022. Hospitalization rate, inpatient characteristics, various in‐hospital outcomes/complications, and healthcare resource utilization were described. Results: A total of 176,911 RSV‐confirmed outpatients, 153,383 influenza‐confirmed outpatients, 90,413 RSV‐confirmed hospitalizations, and 11,186 influenza‐confirmed hospitalizations were identified. Among outpatients, 24.7% of RSV infection and 2.8% of influenza cases required hospitalization within 1 week. There was no co‐morbidities/prematurity for 95.0% of RSV hospitalizations and 96.5% of influenza hospitalizations. Proportions of in‐hospital outcomes/complications were (RSV infection vs. influenza): oxygen use 47.6% vs. 14.8%, mechanical ventilation 2.1% vs. 0.7%, pneumonia 33.6% vs. 12.8%, otitis media 7.7% vs. 2.3%, febrile seizure 1.5% vs. 34.4%, encephalitis/encephalopathy 0.1% vs. 0.5%, myocarditis < 0.1% vs. 0.6%, antibiotics prescription 48.0% vs. 24.4%. The mean inpatient stay was 6.1 vs. 4.3 days at direct medical costs of 435,744 vs. 315,809 JPY/patient. These trends held true in age‐stratified data. In‐hospital death occurred in 31 RSV infection and 6 influenza cases. Conclusions: Although both infections resulted in substantial burden, RSV infection led to more frequent hospitalizations, worse in‐hospital outcomes, longer inpatient stays, higher medical costs, and more frequent antibiotics prescription compared to influenza. Most RSV hospitalizations occurred among healthy term children, emphasizing the need for prevention measures in all children. [ABSTRACT FROM AUTHOR]

Objective: RSV bronchiolitis is a leading cause of hospitalization in infants and young children. We aimed to document the economic burden and epidemiology of RSV over seven seasons in Southern Austria. Patients and Methods: All RSV‐associated hospitalized (PCR‐proven) children ≤ 5 years of age between 1 October 2015 and 30 April 2022 were collected retrospectively. Demographic and epidemiologic data, along with hospitalization costs (direct and indirect), were calculated. Results: Among 976 children hospitalized due to RSV infection, 87% were healthy term infants, and 79% were < 12 months old. Prematurity (13%) and pre‐existing conditions (11%) significantly impacted older children—59% of cases in the 2nd compared with 68% in the 1st year of live. RSV‐related hospital costs were approximately €2.0 millions per year (of a total of 60 millions per year). RSV accounted for 19% of hospitalizations due to acute respiratory illness (ARI) in children ≤ 5 years, 37% of all ARI < 6 months, 28% of all ARI < 12 and 6.3% of all‐cause hospitalizations < 12 months of age, respectively. Conclusions: Every 5th hospitalization due to respiratory illness in children ≤ 5 years of age was associated with RSV, representing 7.9% of all hospitalizations and 3.3% of all paediatric hospitalization costs. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory infections worldwide, including Thailand. This study aimed to assess clinical and economic burdens of RSV infections across different age groups in Thailand. Method: A retrospective cohort study was conducted using data from a tertiary care hospital from 2014 to 2021. Patients who tested at least one positive RSV were included and stratified into five age groups (< 2, 2–5, 5–18, 18–65, and > 65 years). Healthcare resource utilization, direct medical costs, and clinical outcomes were analyzed with descriptive statistics. Generalized linear models with gamma distributions and log link were used to model cost outcomes. Costs were reported in 2021 US dollars (USD), with 1 USD = 31.98 Thai Baht. Results: A total of 2122 RSV‐positive patients were identified, half of which (1097) were hospitalized. The median (interquartile range [IQR]) total hospitalization costs ranged from USD780 (IQR: USD488–USD1185) in those < 2 years to USD2231 (IQR: USD1250–USD4989) in those aged 65+ years. Case fatality rates among hospitalized patients also varied from 2.5% to 28.4% depending on age. Increased age, presence of comorbidities, and need for critical care were associated with higher hospitalization costs. Conclusion: Among RSV‐positive patients, younger children experienced the greatest burden, but poorer outcomes were observed in older adults. Higher costs were associated with older age, comorbidities and critical care needs. Understanding RSV economic burdens is crucial for assessing the cost‐effectiveness and public health value of vaccination programs that prioritize at‐risk groups to mitigate the public health impact. [ABSTRACT FROM AUTHOR]

In the present studies, the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment alters the microbiome in conjunction with immune responses presents striking data. The overall findings identify that although steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17 expression. Analysis of the lung and gut microbiome suggested that there are differences in RSV exacerbation that are further altered by fluticasone (FLUT) treatment. Using metagenomic inference software, PICRUSt2, we were able to predict that the metabolite profile produced by the changed gut microbiome was significantly different with multiple metabolic pathways and associated with specific treatments with or without FLUT. Importantly, measuring plasma metabolites in an unbiased manner, our data indicate that there are significant changes associated with chronic allergen exposure, RSV exacerbation, and FLUT treatment that are reflective of responses to the disease and treatment. In addition, the changes in metabolites appeared to have contributions from both host and microbial pathways. To understand if airway steroids on their own altered lung and gut microbiome along with host responses to RSV infection, naïve animals were treated with lung FLUT before RSV infection. The naïve animals treated with FLUT before RSV infection demonstrated enhanced disease that corresponded to an altered microbiome and the related PICRUSt2 metagenomic inference analysis. Altogether, these findings set the foundation for identifying important correlations of severe viral exacerbated allergic disease with microbiome changes and the relationship of host metabolome with a potential for early life pulmonary steroid influence on subsequent viral-induced disease. NEW & NOTEWORTHY: These studies outline a novel finding that airway treatment with fluticasone, a commonly used inhaled steroid, has significant effects on not only the local lung environment but also on the mucosal microbiome, which may have significant disease implications. The findings further provide data to support that pulmonary viral exacerbations of asthma with or without steroid treatment alter the lung and gut microbiome, which have an impact on the circulating metabolome that likely alters the trajectory of disease progression. [ABSTRACT FROM AUTHOR]

While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19. [ABSTRACT FROM AUTHOR]

The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a lack of ideal animal models. Despite the demonstration of efficacy in animal studies, numerous RSV vaccine candidates have been unsuccessful in clinical trials, primarily due to the lack of suitable animal models. The most commonly utilized animal models for RSV research are cotton rats, mice, lambs, and non-human primates. These animals have been extensively employed in mechanistic studies and in the development and evaluation of vaccines and therapeutics. However, each model only exemplifies some, but not all, aspects of human RSV disease. The aim of this study was to provide a comprehensive summary of the disease symptoms, viral replication, pathological damage, and enhanced RSV disease (ERD) conditions across different RSV animal models. Furthermore, the advantages and disadvantages of each model are discussed, with the intention of providing a valuable reference for related RSV research. [ABSTRACT FROM AUTHOR]

One of the greatest success stories of modern medicine is the prevention of infectious diseases by vaccination, most notably against smallpox and poliomyelitis. However, recent events, such as the 2009–2010 swine flu and the 2020 COVID-19 pandemics, as well as the continued emergence of highly pathogenic avian influenza viruses highlighted the fact that we still need to develop new vaccines, and perhaps we should be proactive, rather than reacting to epidemics and pandemics. However, the development of tools for evaluating novel vaccines has not been able to keep up with the rate of vaccine production. Humoral and cellular immune responses to vaccination have both been suggested to be important in preventing infections or ameliorating their consequences, although there is uncertainty regarding their exact roles and importance. This, together with the rapid development of new vaccines, means that the need for developing immunogenicity parameters, and even more importantly, reliable correlates of protection, is more important than ever. [ABSTRACT FROM AUTHOR]

Objectives We examined trends in patient volumes and care intensity among children admitted with laboratory-confirmed respiratory viral infections over 5 years in Ottawa, following the most recent and intense respiratory viral season experienced throughout the Ontario paediatric health system. Methods This was a retrospective cohort study of patients at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa, who were diagnosed with a laboratory-confirmed respiratory viral infection in the first 72 h of admission between October 22, 2017 and March 25, 2023. Their admissions were stratified by age groups and level of care intensity, based on unit of admission and/or additional ventilatory needs, with Level 3 patients requiring intensive care unit admission, and evaluated for trends over six surveillance periods that began in Week 35 (early September) and ended in Week 34 (end-August) of the following year. Results During the surveillance period from August 28, 2022 to March 25, 2023, there was an early, steep and twofold increase in admissions due to respiratory viral infections compared to previous periods, driven largely by Respiratory Syncytial Virus and Influenza A. Despite similar age distributions, there was a larger volume of Level 2 and 3 admissions, and higher proportion of patients requiring Level 2 care intensity in inpatient medicine units (23.4% versus 10.4% in pre-pandemic years; P < 0.001). Conclusions The most recent viral season was associated with elevated volumes and higher inpatient acuity compared to previous years and underscores the need for additional operational and human health resources to support paediatric health systems through these predictable surge periods. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants. [ABSTRACT FROM AUTHOR]

Introduction: Lower respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) is common among young children in Argentina. Use of the currently available prophylactic agent is limited to children aged ≤ 2 years with selected high-risk conditions, and thus the majority of infants remain unprotected. We estimated the value-based price (VBP) of a novel RSVpreF vaccine for use among pregnant people for prevention of RSV-LRTI among infants during the first year of life. Methods: Clinical outcomes and economic costs of RSV-LRTI during infancy and expected impact of RSVpreF vaccination during pregnancy were projected using a population-based Markov-type cohort model. Model results—estimated on the basis of gestational age at birth, disease/fatality rates, and mother's vaccination status—include total numbers of RSV-LRTI cases, RSV-LRTI-related deaths, and associated costs. Base case analyses (RSVpreF vs. no vaccine) were conducted from the healthcare system perspective. Probabilistic sensitivity analyses (PSA; 1000 replications) were also conducted. Willingness-to-pay (WTP) was $10,636 per quality-adjusted life-year (QALY; i.e., 1 × 2021 gross domestic product [GDP] per capita) in base case analyses and PSA. Costs are reported in USD, estimated on the basis of the June 22, 2023 exchange rate. Results: Use of RSVpreF among 342,110 pregnant persons provided protection to 330,079 infants at birth. In total, RSVpreF prevented 3915 RSV hospitalizations, 6399 RSV cases requiring emergency department care, 6182 RSV cases requiring a physician office visit, and 67 disease-related deaths. Direct costs were projected to be reduced by $5.0 million. With 2061 QALYs gained and vaccine administration cost of $1.4 million, the VBP of RSVpreF was estimated to be $74.46 per dose. In PSA, mean VBP was $75.02 (95% confidence interval 54.24–97.30). Conclusions: RSVpreF among pregnant persons would significantly reduce the clinical and economic burden of RSV-LRTI among infants in Argentina and would be considered a cost-effective intervention up to a price of approximately $75. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. Methods: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. Results: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. Conclusions: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6–24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding. [ABSTRACT FROM AUTHOR]

This retrospective study aims to analyze the baseline characteristics and factors associated with poor outcomes in patients with necrotizing enterocolitis (NEC) complicating respiratory syncytial virus (RSV) infection. Using the Virtual Pediatric Systems data registry, patients under 2 years admitted to the pediatric intensive care unit (PICU) were screened. Patients with documented RSV infection and NEC, intestinal perforation, noninfectious gastroenteritis/colitis, or pneumatosis intestinalis occurring around the timing of RSV bronchiolitis diagnosis were included. Out of the screened patients, 41 were analyzed. Most patients (93%) were aged 30 days to 2 years, one-third had baseline anatomical cardiac defects, and 20% history of prematurity. Median PICU length of stay was 11.7 days. Seven patients died before hospital discharge. While not statistically significant, nonsurvivors tended to exhibit higher PRISM-3 scores, more acidemia, and lower systolic blood pressure. These findings emphasize the need for cautious assessment of gastrointestinal symptoms in critically ill patients with RSV infection. [ABSTRACT FROM AUTHOR]

Objectives: This study assesses the effectiveness of nirsevimab, a monoclonal antibody, in preventing medically attended respiratory syncytial virus-lower respiratory tract infections (RSV-LRTI) in a large primary care network in Spain, in both overall and catch-up infants under ten months of age. Methods: The 2023-24 immunization campaign with nirsevimab in Spain targeted all infants born after April 1st, 2023. Those born after October 1st received it at birth in hospitals, while others received it through a catch-up program. The MEDIPRIM network of primary care centers recruited all infants with LRTI for RSV PCR testing and employed a test-negative design (TND) approach to estimate the effectiveness of nirsevimab. Results: The study included 160 infants, 141 (88%) of them received nirsevimab and 128 belonged to the catch-up group (88% received nirsevimab). Overall, RSV was detected in 44 infants (27.5%). Within the catch-up group, 37 (28.9%) were positive for RSV. The overall effectiveness was 75.8% (95% CI: 40.4-92.7), and 80.2% (95% CI: 44.3-95.4) in infants belonging to the catch-up group. Conclusions: This study underscores the effectiveness of nirsevimab in preventing medically attended LRTI in infants in outpatient settings and emphasizes the importance of a catch-up immunization program to reduce the disease burden in primary care. [ABSTRACT FROM AUTHOR]

BACKGROUND: Data describing respiratory syncytial virus (RSV) neutralizing antibody (nAb) levels for nirsevimab, a recently approved, extended half-life, anti-RSV fusion protein (F protein) monoclonal antibody, relative to the previous standard of care, palivizumab, have not been reported. METHODS: MEDLEY was a randomized, palivizumab-controlled, phase 2/3 study of nirsevimab during 2 RSV seasons (season 1 and 2) in infants born preterm (≤35 weeks' gestational age; dosed season 1 only) or with congenital heart disease or chronic lung disease of prematurity (dosed seasons 1 and 2). Participants were randomly assigned to receive a single dose of nirsevimab followed by 4 monthly placebo doses, or 5 once-monthly doses of palivizumab. Anti-RSV F protein serology (ie, levels of prefusion [pre-F]/postfusion [post-F] conformation antibodies), nirsevimab and palivizumab concentrations, and RSV nAbs were measured in participant serum collected at baseline (pre-dose) and days 31, 151, and 361. RESULTS: Serologic data were similar in seasons 1 and 2. Nirsevimab predominately conferred pre-F antibodies, whereas palivizumab conferred pre-F and post-F antibodies. Nirsevimab and palivizumab serum concentrations highly correlated with nAb levels in both seasons. In season 1, nAb levels in nirsevimab recipients were highest in day 31 samples and gradually declined but remained 17-fold above baseline at day 361. nAb levels in palivizumab recipients increased incrementally with monthly doses to day 151. nAb levels followed similar patterns in season 2. nAb levels were ~10-fold higher with nirsevimab compared with palivizumab across both seasons. CONCLUSIONS: Nirsevimab prophylaxis confers ~10-fold higher and more sustained RSV nAb levels relative to palivizumab. [ABSTRACT FROM AUTHOR]

Aim: To explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared with children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). Methods: In 34,214 children aged 1 month to 5 years who were registered as having one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N = 128), RSV infection (N = 4,009), or other RTIs (N = 34,458) from 2017 to 2021, we used a difference-in-differences study design to investigate individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified by infants (1 to 11 months) and children (1 to 5 years). Results: We found a slight increase in primary health care use in the first 4 weeks after the hospital visit for infants with COVID-19 when compared with infants with RSV infection (6 per 10,000; 95% CI [2, 13], a 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared with infants with RSV infection, which lasted for 12 weeks. Conclusions: Our findings imply a slightly increased health care use among infants after a hospital visit for COVID-19 than among infants with other RTIs, the potential etiological mechanisms of which deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services. [ABSTRACT FROM AUTHOR]

Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases. Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases. RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults aged ≥ 60 years with pulmonary diseases. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen–pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections. [ABSTRACT FROM AUTHOR]

During the 2022-2023 respiratory virus season, news media coverage of Respiratory Syncytial Virus (RSV) in the United States and Canada primarily focused on pediatric populations, with limited attention given to older adults and pregnant individuals, despite higher mortality rates in the latter groups. The availability of vaccines targeting older adults and pregnant individuals led to increased media coverage in May 2022, but this was still significantly lower than coverage of pediatric cases. Ageism and risk aversion related to pregnancy may have influenced the disproportionate reporting. The lack of media attention on RSV among older adults and pregnant individuals could contribute to complacency around vaccination in these populations. [Extracted from the article]

Introduction: Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities. Methods: To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -postfusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study. Results: Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms. Discussion: This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a datadriven approach. [ABSTRACT FROM AUTHOR]

Background: RSV is a common seasonal cause of respiratory infections in children and potentially adults and is considered a major cause of mortality and morbidity. While several studies on RSV have been conducted in Saudi Arabia, none have specifically focused on the southwestern region, where distinct climatic and demographic factors may influence RSV pattern. The current study aims to describe five years of experience with RSV cases among hospitalized patients and factors associated with intensive care admission from a tertiary hospital. Materials and Methods: The study adopts a retrospective observational design, focusing on suspected respiratory infection cases confirmed by rapid RSV antigen tests from 2015 to 2020. Data including age, sex, comorbidities, and outcomes were collected from a tertiary hospital's medical records and microbiology laboratory files. Data were analyzed using a t-test and chi-square test. Results: Among 195 participants, primarily pediatric, monthly, and yearly admissions varied. Monthly variations revealed a U-shaped pattern with most cases reported during January, with a decline in 2020. Oxygen support was required for 40% of cases, and comorbidities were observed in 49.23%. Associations between ICU admission and factors like age, gestational age, ventilation, comorbidities, and length of stay were significant. Conclusion: RSV infection is one of the important causes of morbidity and intensive care admission among infants and young children in Saudi Arabia. As reported by others, the seasonality of RSV is evident. Despite higher prevalence in a younger population, physicians should consider RSV in adults and older patients. Further national studies are required for a better estimation of the RSV burden on the country. [ABSTRACT FROM AUTHOR]

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: To evaluate the health benefits, costs, and cost-effectiveness of vaccination with bivalent respiratory syncytial virus stabilized prefusion F vaccine (RSVpreF) for the prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) in Greek adults 60 years of age and older. Methods: A Markov model was adapted to simulate lifetime risk of health and economic outcomes from the public payer's perspective over a lifetime horizon. Epidemiology, vaccine effectiveness, utilities, and direct medical costs (EUR, 2024) were obtained from published studies, official sources, and local experts. Model outcomes included the number of medically attended RSV cases, stratified by care setting (i.e., hospital, emergency department [ED], outpatient visits [OV]), and attributable RSV-related deaths, costs, life years (LY), quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICERs) of RSVpreF vaccination compared with no vaccination. Results: The model projected 258,170 hospitalizations, 112,248 ED encounters, 1,201,604 OV, and 25,463 deaths related to RSV in Greek older adults resulting in direct medical costs of EUR 1.6 billion over the lifetime horizon. Assuming RSV vaccination would reach the same coverage rates as pneumococcal and influenza programmes, 18,118 hospitalizations, 7874 ED encounters, 48,079 OV, and 1706 deaths could be prevented over the modelled time horizon. The health benefits associated with RSVpreF contributed to an incremental gain of 10,976 LYs and 7230 QALYs compared with no vaccination. The incremental analysis reported that vaccination with RSVpreF was estimated to be a cost-effective strategy resulting in ICERs of EUR 12,991 per LY gained, EUR 19,723 per QALY gained, and EUR 7870 per hospitalized RSV case avoided compared with no vaccination. Conclusions: Vaccination with RSVpreF was a cost-effective strategy for the prevention of RSV disease in Greek adults over 60 years of age. The introduction of RSV vaccination can improve public health by averting RSV cases and deaths and has the potential to fulfil an unmet medical need. [ABSTRACT FROM AUTHOR]

Background: Acute viral respiratory tract infections constitute a significant challenge in pediatric healthcare globally, with rhinovirus representing one of the primary etiological agents. In this context, we conducted a study with the objective of identifying the clinical characteristics and outcomes of rhinovirus infection in comparison with other respiratory viruses in children hospitalized in one of the largest pediatric hospitals in the capital of Romania. Methods: We conducted a retrospective study among children hospitalized for influenza-like illness symptoms and who were tested by multiplex RT-PCR with a nasopharyngeal swab between May 2020 and December 2021. Results: A total of 496 children were eligible for inclusion in the study, and the positivity rate for at least one virus was 58.5%. The rhinovirus was identified in 138 patients (median age 12.5 months), representing 27.8% of all children tested and 49.3% of all positive samples. Although the clinical features of children with rhinovirus were dominated by cough (63.7%) and dyspnea (51.6%), no symptoms were identified that were strongly associated with rhinovirus infection in comparison to other respiratory viruses. The probability of receiving an antibiotic prescription was 1.92 times lower (p = 0.011) in children who tested positive for rhinovirus compared to children with negative RT-PCR results. The incidence of acute bronchiolitis or acute bronchitis, acute respiratory failure, and acute otitis media was higher among rhinovirus-positive children than among those who tested negative via RT-PCR. However, the incidence of these conditions was similar among children who tested positive for other respiratory viruses. Conclusions: Rhinovirus was the most prevalent virus identified in children hospitalized with influenza-like illness symptoms. The utilization of multiplex RT-PCR molecular tests is instrumental in elucidating etiology with precision and implementation of these advanced diagnostic methods, which can bring significant benefits in practice. A positive result for rhinovirus helps to reduce the unnecessary administration of antibiotics and optimizes patient management, thus decreasing the risk of severe complications such as acute respiratory failure and acute otitis media. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical profile and outcomes in neonates hospitalized with respiratory syncytial virus (RSV) infection. Methods: Clinical features, respiratory support, pharmacological treatment, complications and outcomes of neonates admitted to the neonatal intensive care unit with RSV infection between January 2018 and March 2023 were recorded. Descriptive statistics were employed for analysis. Results: Thirty-seven neonates with RSV infection were analyzed. The most common presenting features were cough (n = 29, 74.4%), refusal to feed (n = 29, 74.4%) and apnea (n = 7, 17.9%). 19 (48.7%) neonates were mechanically ventilated, 28 (71.8%) required noninvasive respiratory support and 13 (35.1%) required bronchodilator therapy. All neonates were discharged after a median (IQR) duration of 14 (9, 23.5) days. Conclusion: Neonates with RSV infection requiring hospitalization have considerable respiratory morbidity requiring prolonged respiratory support and pharmacological therapy. [ABSTRACT FROM AUTHOR]

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFa, CXCL8, ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLSDA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in infants and toddlers. Since natural infections do not induce persistent immunity, there is the need of vaccines providing long-term protection. Here, we evaluated a new adenoviral vector (rAd) vaccine based on the rare serotype rAd19a and compared the immunogenicity and efficacy to the highly immunogenic rAd5. Given as an intranasal boost in DNA primed mice, both vectors encoding the F protein provided efficient protection against a subsequent RSV infection. However, intramuscular immunization with rAd19a vectors provoked vaccine-enhanced disease after RSV infection compared to non-vaccinated animals. While mucosal IgA antibodies and tissue-resident memory T-cells in intranasally vaccinated mice rapidly control RSV replication, a strong anamnestic systemic T-cell response in absence of local immunity might be the reason for immune-mediated enhanced disease. Our study highlighted the potential benefits of developing effective mucosal against respiratory pathogens. [ABSTRACT FROM AUTHOR]

Background/Objective: Respiratory syncytial virus (RSV) is a major cause of bronchiolitis in infants and young children. Bronchiolitis, an acute inflammation of the lower respiratory tract, can lead to pneumonia, respiratory failure, and death. We aimed to compare the incidence and severity of RSV infection in children aged 0–60 months before and during the coronavirus disease 2019 (COVID‐19) pandemic. Methods: A retrospective chart review was conducted on patients aged 0–60 months who tested positive for RSV between May 1, 2018, and May 31, 2022, in a community hospital in Queens County, New York City, United States. Comparisons were made between seasons 2018–2019 and 2019–2020 as before, and seasons 2020–2021 and 2021–2022 as during the COVID‐19 pandemic. Severity of RSV infection was assessed using the Bronchiolitis Severity Score (BSS). Data were analyzed using R software, a p value of < 0.05 was considered statistically significant. Results: The incidence of RSV infection in seasons 2018–2019 and 2019–2020 peaked from mid‐October to February, whereas the first season during the COVID‐19 pandemic (2020–2021) was truncated with a very low incidence of RSV infection, and season 2021–2022 peaked from September to January, with the highest incidence (37%) and lower frequency of RSV infection at any given point. Patients during the season 2021–2022 were older (H [2, 196.6] = 12.5, p < 0.001, 95% CI = [5.4, 25.6]) and had milder illness (H [2, 187.5] = 7.5, p < 0.01, 95% CI = [2.1, 19.2]). Conclusions: We observed a lower incidence of RSV infection and a lower rate of hospitalization for RSV during the COVID‐19 pandemic. The second RSV season during the COVID‐19 pandemic began earlier, lasted longer, and had a lower frequency. Older children with milder illnesses were affected most during this season. RSV epidemiology and disease burden were impacted by the COVID‐19 pandemic and could have significant ramifications for its prevention and control strategies. [ABSTRACT FROM AUTHOR]

Background: Recently, several novel RSV immunisation products that protect infants and older adults against RSV disease have been licensed in Europe. We estimated the effectiveness and efficiency of introducing these RSV immunisation strategies in Germany. Methods: We used a Bayesian framework to fit a deterministic age-structured dynamic transmission model of RSV to sentinel surveillance and RSV-specific hospitalisation data in Germany from 2015 to 2019. The calibrated model was used to evaluate different RSV intervention strategies over 5 years: long-acting, single-dose monoclonal antibodies (mAbs) in high-risk infants aged 1–5 months; long-acting mAbs in all infants aged 1–5 months; seasonal vaccination of pregnant women and one-time seasonal vaccination of older adults (75 + /65 + /55 + years). We performed sensitivity analysis on vaccine uptake, seasonal vs. year-round maternal vaccination, and the effect of under-ascertainment for older adults. Results: The model was able to match the various RSV datasets. Replacing the current short-acting mAB for high-risk infants with long-acting mAbs prevented 1.1% of RSV-specific hospitalisations in infants per year at the same uptake. Expanding the long-acting mAB programme to all infants prevented 39.3% of infant hospitalisations per year. Maternal vaccination required a larger number to be immunised to prevent one additional hospitalisation than a long-acting mAB for the same uptake. Vaccination of adults older than 75 years at an uptake of 40% in addition to Nirsevimab in all infants prevented an additional 4.5% of all RSV hospitalisations over 5 years, with substantial uncertainty in the correction for under-ascertainment of the RSV burden. Conclusions: Immunisation has the potential to reduce the RSV disease burden in Germany. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention. Author summary: Respiratory tract infections caused by RSV present a significant public health concern, especially affecting infants and the elderly. Effective antiviral strategies are urgently needed against this non-segmented, negative-sense RNA virus of the Pneumoviridae family. Our research reveals how RSV maintains replication fitness despite oxidative damage, a common exacerbator of respiratory conditions. We have identified a mechanism where RSV preserves its genome integrity under oxidative stress using the DNA repair enzyme OGG1. This enzyme ensures that the viral RNA accurately pairs 8-oxoGua with cytosine, crucial for maintaining the fidelity of the viral genome. Targeting the interplay between OGG1 and RSV RNA offers a promising approach for developing novel antiviral treatments, potentially countering the virus's evolutionary adaptations. [ABSTRACT FROM AUTHOR]

Background We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. Methods This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. Results Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06–1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. Conclusions Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. Clinical Trials Registration NCT05568797 [ABSTRACT FROM AUTHOR]

Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions. Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds. Clinical Trial Registration ClinicalTrials.gov : NCT05590403. [ABSTRACT FROM AUTHOR]

Background Data on the true prevalence of respiratory syncytial virus (RSV) among medically attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over 3 seasons, which is informative in light of the recommendations for shared decision making for vaccination in older adults. Methods Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated multimorbidity-weighted index (MWI) were collected by in-person survey and electronic medical record review. Results Over 3 surveillance seasons (fall 2017 to spring 2020), 9.9% (n = 441) of 4442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months to 4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). Conclusions RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision making for vaccination. [ABSTRACT FROM AUTHOR]

Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer's patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases. [ABSTRACT FROM AUTHOR]

Rationale: Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. Objectives: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Methods: Participants were recruited at specialist clinics in London, United Kingdom, and Groningen, the Netherlands, beginning in 2017 and observed for three consecutive RSV seasons, during exacerbations, and at least twice yearly. RSV infections were detected by RT-PCR and serologic testing. Measurements and Main Results: A total of 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8.7% of the total); of these, seven were detected only by PCR, 16 only by serology, and four by both methods. Increases in RSV-specific Nucleoprotein antibody were as sensitive as those in the antibody to Pre-Fusion or Post-Fusion for serodiagnosis of RSV-related exacerbations. Conclusions: RSV is associated with 8.7% of outpatient-managed COPD exacerbations in this study. Antibodies to RSV Nucleoprotein may have diagnostic value and are potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion As early detection of deterioration is a challenge in children, the Swedish Paediatric Early Warning Score (SwePEWS) is used to systematically assess paediatric patients' clinical state. Here, we aimed to evaluate the use and predictive ability of SwePEWS.Electronic health records of paediatric patients admitted due to respiratory syncytial virus infection or COVID‐19 were reviewed retrospectively. Registered vital signs were compared to the assigned SwePEWS score and monitored vital sign values to identify discrepancies. Additionally, SwePEWS's ability to predict transfer to the paediatric intensive care unit (PICU) was assessed.Among 1374 SwePEWS assessments, one‐third were either incomplete or contained errors. Incomplete SwePEWS assessments were more frequent during night‐time. Single measurements of oxygen saturation presented lower values compared to average saturation from continuous monitoring. SwePEWS's ability to predict PICU transfer was low.There was a surprisingly high occurrence of underestimated SwePEWS scores. This study provides new insights into pitfalls when developing and implementing paediatric early warning scores for systematic re‐evaluations in paediatric patients. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV+ children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV+ children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV+ children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV+ patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV+ patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children. Editor's summary: Nearly all children are infected with respiratory syncytial virus (RSV) by 2 years of age. Although most children only develop mild symptoms, some can develop severe diseases requiring hospitalization. To better understand the potential drivers of severe disease, Reilly et al. analyzed airway and peripheral blood immune cells from pediatric patients infected with RSV requiring hospitalization. The authors found that natural killer (NK) cells were increased in the airways of children with severe RSV. A corresponding decrease was observed in peripheral blood NK cells. Moreover, the NK cells exhibited an altered phenotype and were less effective at killing target cells ex vivo. These data suggest that these NK cells may be drivers of RSV immunopathology. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is the most common cause of hospitalisation in infants aged ≤ 6 months in Western countries. Nearly 1,500 infants under six months of age are hospitalised with RSV annually in Denmark. This nationwide study describes the healthcare resource utilisation and costs related to RSV hospitalisation in this vulnerable age group. Methods: RSV cases were identified in the Danish National Patient Register. Infants were included if they at the age of 0–5 months had a (1) respiratory related hospital admission (duration > 12 h), (2) within 10 days of a positive RSV test, (3) between January 2013 and December 2022. Each case was matched with five individuals never diagnosed with RSV on age, sex, region of residence, birth (pre/full term), number of siblings < 7 years old, and parents' education. An episode of RSV was defined as the seven days prior to hospitalisation to 30 days after initial hospitalisation. Study outcomes included contacts with hospital and primary care, and total healthcare costs defined as the sum cost of hospital care, primary care, and prescription medicine. Cost and contacts attributable to RSV was calculated in a diff-in-diff framework, as the difference between case and reference group. Results: The study population comprised of 8,428 RSV cases and 41,725 reference individuals. Cases generated 1.58 (p < 0.001) attributable inpatient contacts, 0.84 (p < 0.001) outpatient contacts, and 1.19 (p < 0.001) primary care contacts during their RSV episode. An additional 0.6 (p < 0.001) inpatient, 1.08 (p < 0.001) outpatient and 2.42 (p < 0.001) primary care contacts were attributed to RSV in the year following the RSV episode. Total cost of an RSV episode was EUR 2,997 (p < 0.001) with an additional EUR 1,428 (p < 0.001) in the following year. Conclusion: RSV hospitalisations of infants are associated with substantial healthcare utilisation and costs. The same pattern was observed in the year following the RSV episode. If the new RSV prevention options are introduced nationwide, the overall burden of RSV is expected to be substantially reduced in the future. [ABSTRACT FROM AUTHOR]

Background: Respiratory Syncytial Virus (RSV) is an important pathogen causing acute respiratory illnesses in adults. RSV infection can lead to severe outcomes, including hospitalizations and even death. Despite the increased recognition of the burden in older adults, immediate post-discharge care needs among adults hospitalized with RSV are not well characterized and have not been compared to other serious medical conditions (such as influenza, acute myocardial infarction (MI), and stroke) for which there have been long-standing disease prevention efforts. Objectives: This study aims to describe the immediate post-discharge care needs among adults hospitalized with RSV in the United States and descriptively compare it to those hospitalized with influenza, acute MI, or stroke. Design: Retrospective observational cohort study. Patients: Adults aged ≥ 18 years, hospitalized with a primary diagnosis of RSV, influenza, acute MI, or stroke from January 01, 2016, to December 31, 2019, were identified from the Premier Healthcare Database using the International Classification of Diseases (ICD-10) codes. Main measures: Immediate post-discharge care was categorized into three different levels of care based on the discharge dispositions. Descriptive analyses were performed. Key results: In total, 3,629 RSV, 303,577 influenza, 388,682 acute MI, and 416,750 stroke hospitalizations were identified, the majority occurred among patients aged ≥ 65 years. Professional home care needs were the highest for RSV hospitalizations (19.1%), followed by influenza (17.7%), stroke (15.4%), and acute MI (9.8%). Additionally, institutional care needs immediately following discharge were similar for RSV, influenza, and acute MI hospitalizations (14.2%, 15.8%, and 14.1%, respectively). Conclusions: Immediate post-discharge care needs among adults hospitalized with RSV, especially in older adults, can be considerable and comparable to influenza and acute MI discharges. With recently approved RSV vaccines, efforts to increase vaccination in older adults are needed to prevent RSV and associated healthcare consequences. [ABSTRACT FROM AUTHOR]

Objective: Lower respiratory tract infections (LRTI) are among the major causes of mortality in children worldwide. Our study aimed to determine viral agents in children under five years of age who were followed up with acute LRTI. Methods: Nasopharyngeal swab samples were taken from children aged 1 month to 5 years who were diagnosed with LRTI at the Bezmialem Vakıf University pediatric emergency department between March 1, 2015 and January 31, 2016. Cases with underlying chronic diseases were excluded from the study. The presence of the agent was investigated in the samples taken using the real-time polymerase chain reaction method. The distribution of cases in which the agent was detected according to age groups and seasons was examined. The relationship between the agent and the clinical and laboratory findings was investigated. Results: Of the 95 patients included in the study, 51 (53.7%) were male, 44 (46.3%) were female, and the mean age was 26.2 months. The presence of viruses was shown in 50 cases (52.6%). The most frequently detected viruses were rhinovirus (28%), human bocavirus (HBoV) (26%) and respiratory syncytial virus (RSV) (24%). While RSV infections were more common in winter months, HBoV was observed to persist throughout the year. No significant relationship was found between the clinical and laboratory findings of the patients and the agents. Conclusion: Viral etiology was detected in 52.6% of the cases. Molecular tests are valuable in detecting more than one virus in the distribution of viruses among different age groups. [ABSTRACT FROM AUTHOR]

Background: Vaccine‐preventable respiratory infections impact on healthcare systems globally. Despite availability of vaccines, fluctuations in vaccination rates, pathogen virulence and community transmission dynamics mean that these respiratory infections continue to pose substantial public health risks. To understand trends in vaccine‐preventable respiratory infections, we analysed linked data from emergency department (ED), hospitalisations and deaths in New South Wales, Australia, from 2012 to 2022. Methods: ED presentations with respiratory infection like illness were linked to hospitalisation and death records. Age‐standardised rates of ED presentations, proportions subsequently hospitalised for acute respiratory infection (ARI) and specific vaccine‐preventable disease diagnoses and 28‐day mortality rates were estimated by year and age. Results: From 2012 to 2022, there were 3,127,090 ARI‐like ED presentations. Age‐standardised rates increased until 2020, declined in 2021 and rebounded in 2022. Across all years, of these ARI‐like ED presentations, 16.6% were hospitalised for acute respiratory infections, including pneumonia (7.9%), influenza (1.1%), RSV disease (1.3%), COVID‐19 (0.8%) and pneumococcal disease (0.3%). Proportions hospitalised were highest in those aged 65+ years, except for RSV, which was highest in children aged 0–4 years. The highest 28‐day mortality post‐ARI‐like ED presentation was observed with COVID‐19 in adults aged 65+ years at 13.1%. Conclusions: This study highlights the continuing burden of vaccine‐preventable respiratory infections on an Australian healthcare system. These data can be used to monitor the effectiveness of vaccination programmes and other public health interventions. Future efforts should focus on enhancing surveillance and data linkage to improve precision and guide targeted public health strategies. [ABSTRACT FROM AUTHOR]

Nirsevimab is a long-acting monoclonal antibody that can prevent respiratory syncytial virus (RSV) infection in infants. RSV is a common virus that can cause serious respiratory infections in newborns and infants, particularly those with certain risk factors. Nirsevimab is more effective than the previously available intervention, palivizumab, and has a longer duration of protection. It is recommended for infants entering their first RSV season, especially those at increased risk of severe RSV disease. Nirsevimab has been shown to be safe and has minimal side effects. Programs to administer nirsevimab are being implemented in various countries, including Canada. [Extracted from the article]

Introduction: Respiratory syncytial virus (RSV) is a leading cause of respiratory illness in infants globally, with new maternal RSV vaccines on the horizon. Vaccine decision-making during pregnancy is shaped by individual, interpersonal, community, and societal factors. This study explored key interpersonal influences on maternal vaccine decision-making among pregnant and lactating people (PLP) and community members in Kenya. Methods: This qualitative study conducted in-depth interviews with six pregnant people, 18 lactating people, and 10 community members in one rural and one urban county in Kenya. Data were analyzed using a grounded theory approach. Results: Participants identified the pregnant person themself, male partners, other family members, peers, and healthcare providers (HCPs) as key influences on the maternal immunization decision-making process. The majority of interviewed PLP believed that decision-making during pregnancy should be left to themselves due to autonomy and their role as the primary caregiver. Community members, including male partners, also identified pregnant people as the key decision-maker. While some PLP said they deferred to male partners to make vaccine decisions, more felt that men were not as informed on maternal and child issues as themselves or other female peers and relatives. HCPs emerged as important influences and information sources for PLP during decision-making. Discussion: Understanding who influences vaccine-decision making during pregnancy will help inform demand generation strategies, and in turn, uptake of future maternal vaccines, including RSV vaccines. Given the strong role HCPs and peers have in the decision-making process, targeting key potential influences is essential to improve vaccine acceptance. Significance: What is Already Known: Maternal immunization saves lives, but the presence of vaccines does not guarantee uptake. Decision-making for maternal vaccines does not occur in a vacuum and is influenced by multiple sources. What this Study Adds: Information on how peers influence future maternal vaccine acceptance is limited. Our findings show that pregnant and lactating people (PLP) believe the decision to vaccinate should be left to themselves due to autonomy and their caregiver role, even in rural Kenya. Additionally, our findings show that PLP are influenced not only by their partners and healthcare providers, but also female family members and peers. As RSV vaccine rollout begins, targeted demand generation strategies for PLP and their influences is paramount. [ABSTRACT FROM AUTHOR]

Background The incidence of respiratory syncytial virus (RSV)–acute respiratory infection (ARI) in community-dwelling adults after the Omicron variant of the COVID-19 pandemic is unknown. Our aim was to assess the incidence of RSV-ARI in adults aged 18 to 64 years over 2 consecutive RSV seasons (October–April 2022–2024) in 4 US states. Methods This community-based prospective cohort study comprised 7501 participants in Minnesota, Wisconsin, Florida, and Arizona. We calculated RSV-ARI and RSV–lower respiratory tract disease (LRTD) incidence and attack rates. We reported unadjusted incidence by age group, gender, race and ethnicity, Charlson Comorbidity Index, socioeconomic status, residential state, and rural/urban setting. Results Seasons 1 and 2 had 2250 and 2377 ARI episodes, respectively, with an RSV-ARI positivity rate of 5.5% for season 1 and 5.8% for season 2 among those tested. In season 1, the overall incidence of RSV-ARI was 27.71 (95% CI, 22.82–33.34) per 1000 person-years (1.49% attack rate). Almost half (49.0%) had RSV-LRTD, with an incidence of 13.53 (95% CI, 10.19–17.61) per 1000 person-years (0.73% attack rate). In season 2, the RSV-ARI and RSV-LRTD incidence rates were 26.39 (95% CI, 21.73–31.75) per 1000 person-years (1.51% attack rate) and 12.43 (95% CI, 9.31–16.26) per 1000 person-years (0.72% attack rate). RSV-ARI incidence peaked in November 2022 and December 2023. Conclusions Our observations suggest that RSV-ARI incidence and seasonal pattern are shifting to prepandemic RSV epidemiology. [ABSTRACT FROM AUTHOR]