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

Background: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. Methods: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000–2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. Results: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. Conclusions: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. Methods During 2016–2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. Results Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A–positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. Conclusions Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes. [ABSTRACT FROM AUTHOR]

Background Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines. Methods We developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the United States. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained as a measure of effectiveness and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective. Results Using a willingness-to-pay of $95 000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD up to $127 with Arexvy and $118 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the United States, the budget impact of these programs at the maximum PPD ranged from $6.48 to $6.78 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $235 for Arexvy and $245 for Abrysvo, with 2-year budget impacts of $11.78 and $12.25 billion, respectively. Conclusions Vaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (m6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6A is also involved in viral entry and whether m6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in children aged less than 5 years in Poland. Methods: This retrospective observational cohort study was based on data obtained from the National Health Fund in Poland regarding all acute respiratory tract infections and RSV-coded admissions of children (age < 5 years) to public hospitals between July 2015 and June 2023. Patients were stratified based on the following age groups: 0–1 month, 2–3 months, 4–6 months, 7–12 months, 13–24 months, and 25–60 months. Results: The number of RSV-related hospitalizations increased every season, both before and through the ending phase of the coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infection. Hospitalization rates per 1000 inhabitants were the highest for children aged 0–12 months, reaching 47.3 in the 2022/23 season. Within this group, the highest hospitalization rate was observed for children aged 2–3 months—94.9 in the 2022/23 season. During the ending phase of the COVID-19 pandemic, the observed increase in admission rates was 2-, 4-, and 5-fold the pre-COVID rate for children aged <12 months, 12–24 months, and 25–60 months, respectively. Conclusions: In Poland, RSV infections cause a significant burden in hospitalized children aged less than 5 years. RSV-related hospitalizations were most frequent in children aged less than 1 year. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infections. After the pandemic, more RSV-related hospitalizations were observed in older children (aged 13 months and older) vs. the pre-pandemic phase. [ABSTRACT FROM AUTHOR]

Introduction: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture–recapture methods provide alternatives for estimating the number of RSV‐related hospitalizations in a population. Methods: Capture–recapture methods were used to estimate the number of RSV‐related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016–2017 to 2019–2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture–recapture estimates weighted by hospitals' market share divided by the corresponding census population. Results: Using capture–recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9–15.4) RSV‐related hospitalizations per 10,000 persons during the 2016–2017 season to 28.4 (95% CI: 18.2–59.0) hospitalizations per 10,000 persons in the 2019–2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture–recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture–recapture estimated hospitalizations. Conclusion: Capture–recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture–recapture allows for a more comprehensive estimate of RSV hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician‐rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient‐reported outcomes (PROs). Methods: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ‐5D‐5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. Results: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between‐pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician‐rated symptoms. Conclusions: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well‐being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. Methods: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. Results: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. Conclusions: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is increasingly recognized as being implicated in acute illness in older adults, with a significant weight in hospitalizations for respiratory illness and death. By means of a best-evidence review, this paper aims to investigate whether RSV can be considered a forgotten pathogen in older patients, looking at trends in the literature volume and exploring possible epidemiological and clinical features underlying the focus given to it. We then present an assessment of its disease burden and present and future strategies for its reduction, particularly in light of the recent availability of new vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied. Methods: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community‐based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow‐up questionnaires completed by the parents of positive children on Days 14 and 30. Results: RSV laboratory‐confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV‐positive swabs. RSV‐positive children were younger than RSV‐negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV‐A positive patients required more additional pediatric examinations than RSV‐B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs. Conclusions: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies. [ABSTRACT FROM AUTHOR]

Background Infants covered by Medicaid have higher respiratory syncytial virus (RSV) hospitalization rates than those with commercial insurance, but findings are limited to the inpatient setting. This birth cohort study describes healthcare encounters for RSV across all settings among infants covered by Medicaid and the Children's Health Insurance Program. Methods Medicaid claims for infants born and residing in Arizona (AZ), California (CA), Florida (FL), Michigan (MI), North Carolina (NC), New York (NY), and Texas (TX) were analyzed for first diagnosis of RSV in 2016–2018 using International Classification of Diseases, Tenth Revision codes. Encounters on the day of first diagnosis were examined by setting in 7 states and by setting and race in CA, FL, and NC. Results A total of 80 945 infants were diagnosed with RSV in 7 states in 2016–2018. The highest encounter rates for first RSV diagnosis were in the emergency department (ED) in 5 states (11.0–33.4 per 1000 in AZ, CA, FL, MI, and NY) and outpatient setting in 2 states (54.8 and 68.5 per 1000 in TX and NC). Significantly higher outpatient encounter rates were found in CA and NC for White infants compared to non-White infants. In NC, ED encounter rates were significantly higher for non-White infants than White infants, whereas in CA, the rates were comparable. In these 2 states, hospitalization rates were similar across groups. In FL, compared with White infants, non-White infants had significantly higher encounter rates in each setting on the day of first RSV diagnosis. Conclusions This is the first study to describe the burden of RSV by setting and race. Medicaid infants who are newly diagnosed with RSV have the highest burden in ED and outpatient settings. [ABSTRACT FROM AUTHOR]

The performance of the Xpert Xpress CoV-2/Flu/RSV plus and Alinity m Resp-4-Plex Assays were evaluated using 167 specimens, including 158 human respiratory specimens and 9 external quality assessment program (EQAP) samples. For respiratory specimens, CoV-2/Flu/RSV plus exhibited perfect agreement with the standard-of-care (SOC) methods (Cohen's κ: 1, 100% agreement). The overall positive and negative percent agreement (PPA and NPA) were 100%, with 95% confidence intervals of 96.50 to 100% and 85.70 to 100%, respectively. On the other hand, Resp-4-Plex revealed an almost perfect agreement with the SOC methods (Cohen's κ: 0.92, 97.71% agreement). The overall PPA and NPA were 100% (95.76 to 100%) and 88.46% (70.20 to 96.82%), respectively. For EQAP samples, the results of CoV-2/Flu/RSV plus (9/9) and Resp-4-Plex (4/4) were concordant with the expected results. The experimental limit of detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the lowest (25 copies/mL for both methods), and that of the respiratory syncytial virus was the highest (400 copies/mL for CoV-2/Flu/RSV plus and 100 copies/mL for Resp-4-Plex). Threshold cycle (Ct) value correlation showed a large positive linear association between CoV-2/Flu/RSV plus and Resp-4-Plex, with R-squared values of 0.92–0.97, and on average, the Ct values of CoV-2/Flu/RSV plus were higher than that of Resp-4-Plex by 1.86–2.78, except for Flu A1 target (−0.66). To conclude, the performance of both assay was comparable to the SOC methods for both upper and lower respiratory specimens. Implementation of these rapid assay may reinforce the diagnostic capacity for the post-pandemic co-circulation of SARS-CoV-2 and other respiratory viruses. [ABSTRACT FROM AUTHOR]

Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I2 statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable "muco‐trapping" variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections. [ABSTRACT FROM AUTHOR]

Background: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context. Methods: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described. Results: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use. Conclusions: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future. [ABSTRACT FROM AUTHOR]

After the decline of the COVID-19 pandemic, health systems were challenged by the simultaneous prevalence of different respiratory viruses causing a wide overlap in symptoms. This increased the demand for multi-virus diagnostic tests which require suitable pre-analytical workflow solutions in order to receive valid diagnostic results. In this context, the effects of specimen storage duration and temperature on the RNA/DNA copy number stability of influenza A/B, RSV A/B, SARS-CoV-2 and adenovirus were examined for four commercially available transport swab systems and saliva collection devices. The respiratory viruses were more stable in the saliva collection devices than in the transport swab systems when stored at RT or 37 °C for up to 96 h. Moreover, no differences between viral nucleic acid stability of enveloped and non-enveloped viruses were observed. The infectivity of all enveloped viruses could be inactivated by the saliva collection device from PreAnalytiX. The Norgen saliva device completely inactivated influenza A/B, while RSV A/B were partially inactivated. The non-enveloped adenovirus was inactivated by a reduction factor of 10E+ 4 in both saliva collection devices. All respiratory viruses remained infectious in the transport swab systems. Two possible transport medium additives were tested which inactivated or strongly reduced viral replication of tested enveloped viruses but had no effect on the non-enveloped adenovirus. Finally the implementation of multi-target detection procedures involving a direct amplification approach was successfully tested by spike-in of all enveloped viruses simultaneously into transport swab systems. This fast and reproducible setup presents a valuable solution for future implementations in multi-virus testing strategies. • Specimen collection, storage, transport and handling influence diagnostic results. • Multi-target detection assays could aid rapid identification of causative pathogens. • Tested saliva collection devices inactivated respiratory viruses used here. • Tested swab systems do not inactivate respiratory viruses used here. • Inactivating additives can reduce the risk of infection for healthcare personnel. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity. Methods Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray. Results While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10−8), we identified 816 candidate SNPs with a P -value of <1 × 10−4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P <.05). Conclusions These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations. [ABSTRACT FROM AUTHOR]

Background There is no consensus on how to best quantify disease severity in infants with respiratory syncytial virus (RSV) and/or bronchiolitis; this lack of a sufficiently validated score complicates the provision of clinical care and, the evaluation of trials of therapeutics and vaccines. The ReSVinet score appears to be one of the most promising; however, it is too time consuming to be incorporated into routine clinical care. We aimed to develop and externally validate simplified versions of this score. Methods Data from a multinational (the Netherlands, Spain, and United Kingdom) multicenter case-control study of infants with RSV were used to develop simplified versions of the ReSVinet score by conducting a grid search to determine the best combination of equally weighted parameters to maximize for the discriminative ability (measured by area under the receiver operating characteristic curve [AUROC]) across a range of outcomes (hospitalization, intensive care unit admission, ventilation requirement). Subsequently discriminative validity of the score for a range of secondary care outcomes was externally validated by secondary analysis of datasets from Rwanda and Colombia. Results Three candidate simplified scores were identified using the development dataset; they were excellent (AUROC >0.9) at discriminating for a range of outcomes, and their performance was not significantly different from the original ReSVinet score despite having fewer parameters. In the external validation datasets, the simplified scores were moderate to excellent (AUROC, 0.7–1) across a range of outcomes. In all outcomes, except in a single dataset for predicting admission to the high-dependency unit, they performed at least as well as the original ReSVinet score. Conclusions The candidate simplified scores developed require further external validation in larger datasets, ideally from resource-limited settings before any recommendation regarding their use. [ABSTRACT FROM AUTHOR]

Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI. [ABSTRACT FROM AUTHOR]

Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score. Methods We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated. Results Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified. Conclusions No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets. [ABSTRACT FROM AUTHOR]

Background During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. Methods We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. Results For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P <.001), whereas duration of respiratory symptoms and was comparable. Conclusions Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572). [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a common pathogen causing mostly cold-like symptoms, but in very young infants and elderly individuals it can lead to severe disease and even death. There are currently promising developments both in vaccine development and in therapeutics that are expected to be approved soon. To get an impression within European countries of the laboratory diagnostics and surveillance activities, in anticipation of these developments, we queried the members of the European Respiratory Syncytial Virus Laboratory Network (RSV-LabNet, under the umbrella of the PROMISE project) via an online survey. The answers from the consortium members showed scattered monitoring and the application of a broad array of techniques in the laboratories. A majority of the members expressed strong interest in harmonization and collaboration for setting up surveillance programs and the need for sharing laboratory protocols. The additional value of RSV whole-genome sequencing is broadly appreciated, but implementation requires further development and closer collaboration. The RSV-LabNet can have an important responsibility in establishing contacts and exchange of expertise and providing a platform for communication to advance diagnostics, preparedness, and surveillance. [ABSTRACT FROM AUTHOR]

Objective The main objective of this report was to comprehensively analyze the clinical characteristics of children hospitalized with respiratory syncytial virus (RSV) infections in 2021 during the coronavirus disease 2019 (COVID-19) pandemic and to compare them with those in the five previous RSV seasons. We hypothesized that the clinical and demographic features of children hospitalized with RSV infection in 2021 were different from those hospitalized in previous respiratory seasons. Study Design In this retrospective observational study, children younger than 2 years hospitalized with RSV bronchiolitis from January 1, 2015, to December 31, 2021, at the Department of Pediatrics of the Hospital Gregorio Marañón, Madrid, Spain, were included. We compared the clinical characteristics of children hospitalized with RSV bronchiolitis in the five seasons before the COVID-19 pandemic and during the subsequent off-seasonal surge of RSV infections. Results We found a significant reduction in hospitalizations for RSV bronchiolitis during the usual winter epidemic period due to the COVID-19 pandemic. Children hospitalized with RSV infection in 2021, during the COVID-19 pandemic, were older than children hospitalized in the prepandemic period (2015–2020; 4.0 [1.6–9.2] vs. 3 [1.5–6.5] months; p < 0.01). We also found shorter duration of oxygen days during the COVID-19 period compared with previous respiratory seasons (3 [2–5] vs. 4 [2–6] days; p = 0.02). Conclusion The COVID-19 pandemic modified the RSV seasonality with a significant reduction in RSV hospitalizations during the expected 2020–2021 season and a reappearance of RSV 7 months later than expected. We also found changes in the median age of children with RSV bronchiolitis during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic compared with the prepandemic RSV seasons and shorter duration of oxygen days suggesting a modest reduction in disease severity. We hypothesize that this observation reflects the lack of RSV circulation in the previous months (April 2020-March 2021), with a larger pool of vulnerable infants that had not been previously infected. Key Points The COVID-19 pandemic shifted RSV seasonality. RSV children hospitalized during the pandemic were older. Modest reduction in disease severity was observed during the pandemic. [ABSTRACT FROM AUTHOR]

Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been approved by Health Canada for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract disease. We estimated the health benefits and cost-effectiveness of these vaccines under a publicly funded single-dose vaccination program in Ontario that targets residents of long-term care homes (LTCHs). Additionally, we evaluated an extended program that broadens vaccination to include community-dwelling older adults. A discrete-event simulation model was parameterised with the burden of RSV disease including outpatient care, hospitalisation, and death among adults aged 60 years or older in Ontario, Canada. Accounting for direct and indirect costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained, and determined the range of price-per-dose (PPD) for vaccination programs to be cost-effective from both healthcare and societal perspectives over two RSV seasons. The incremental cost-effectiveness ratio (ICER) was calculated to estimate the additional costs required to gain one QALY. Using a willingness-to-pay of $50,000 per QALY gained, we found that vaccinating 90% of residents in LTCHs with Arexvy would be cost-effective from a societal perspective for a PPD up to $163, producing a mean ICER value of $49,984 (95% CI: $47,539 to $52,704) per QALY gained with a two-year budget impact of $463,468 per 100,000 older adults. The reduction of hospitalizations was estimated at 7.0% compared to the no-vaccination scenario. Extending the program to include community-dwelling older adults with a 74% coverage akin to influenza vaccination, Arexvy remains cost-effective for a PPD up to $139, with a mean ICER value of $49,698 (95% CI: 48,022 to 51,388) per QALY gained and a two-year budget impact of $8.63 million. Compared to the no-vaccination scenario, the extended program resulted in a 57.3% reduction in RSV-related hospitalisations. Vaccinating residents of LTCHs against RSV disease would be cost-effective depending on PPD; extending the program to community-dwelling older adults would provide substantial health benefits, averting significant direct healthcare costs and productivity losses. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV), a single-stranded RNA virus, is a leading cause of hospitalization in infants, especially ≤ 2 months of life. In the light new immunization strategies adoption, we described epidemiological and clinical characteristics of RSV-associated hospitalizations in pediatric and neonatal intensive care units of the Policlinico Foggia Hospital, Apulia Region, Italy. Methods: Hospitalized children with a laboratory-confirmed RSV infection from 2011 to 2023 were retrospectively evaluated. Clinical information was collected from Hospital Discharge Registry in the period 2011–2020. The proportion of the hospitalization for acute respiratory infections (ARIs) associated to RSV was calculated and the hospitalization cost was analyzed by using the diagnosis-related group reimbursement rate. The anticipated impact of immunization either with monoclonal antibodies or maternal immunization on the number of hospitalizations was estimated. All analyses and quality assessment were performed using STATA/SE15.0. Results: A total of 1,005 RSV-cases were included in the study, of which 86.3% occurred between December-March. In the period 2011–2020, 832 RSV-cases were matched with the corresponding hospital admissions; 75.2% were aged < 1 year (49.6% 0–2 months). Bronchiolitis was the most frequent admission diagnosis occurring in 63.3% of patients; 25% of children were affected by a very severe RSV-disease. Younger age ≤ 2 months (OR:14.8, 95%CI:8.30–26.31, p = 0.000), higher length-of-hospital-stay (OR:1.01, 95%CI:1.0–1.02, p = 0.030) and history of prematurity (OR:4.4, 95%CI:1.57–12.11, p = 0.005) were associated with a higher disease severity. RSV caused 48.9% of ARIs among children < 1 year. The mean cost of an RSV-associated hospitalization was 3,036 euros/year, with the higher cost in the 0–2 months age group (4,225 euros/year). Immunization programs with nirsevimab could prevent 51.4 RSV hospitalizations/year and 18.1 very severe RSV disease/year in infants < 1 year of age. RSV vaccine could prevent 46.1 of hospitalizations/year caused by RSV within 180 days after birth. Conclusions: Our study contributes to outlining the baseline profile of RSV-associated hospitalizations among Italian children by providing epidemiological/clinical/economic estimates. While awaiting new recommendations on immunization, healthcare-workers should persist in implementing public health measures and appropriate case management to control RSV seasonal epidemics. Strengthened laboratory RSV surveillance is needed to inform the implementation of the new immunization strategies. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in people of all ages and is the leading cause of hospitalization among infants in the United States. The year 2023 was exciting for RSV prevention. The Food and Drug Administration (FDA) approved 3 new tools for preventing severe lower respiratory tract RSV infections in infants, young children, and elderly persons. In May 2023, the FDA approved 2 vaccines, RSVpreF3 (Arexvy™, GSK) and RSVpreF (Abrysvo™, Pfizer), for adults ages 60 years or older to be given as a single-dose intramuscular injection. July 2023 brought the approval of the first long-acting monoclonal antibody nirsevimab (Beyfortus™, Sanofi and AstraZeneca) for the prevention of RSV disease in infants and young children. Then in August, the FDA approved a vaccine (Abrysvo™, Pfizer) to be given to pregnant women to protect their newborns through passive immunity. This article focuses on nirsevemab that has been recommended by the Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) to be administered for all infants <8 months of age and for children 8 to 19 months of age who are at increased risk for severe RSV disease. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems. A graphical plain language summary is available with this article. Graphical Plain Language Summary: [ABSTRACT FROM AUTHOR]

Introduction: Respiratory infections are an ongoing global health challenge. The COVID‐19 pandemic triggered global nonpharmacological measures that reshaped public health. In Japan, the shift from legal to individual discretion in pandemic management started on May 8, 2023. However, it still unknown how the relaxation of measures affects respiratory pathogens across age groups. Methods: We collected 16,946 samples from 13,526 patients between February 2020 and September 2023, analyzing the circulating respiratory pathogen dynamics using FilmArray respiratory panel. Results: Our analysis revealed significant increases in the positivity rates of respiratory pathogens across multiple age groups after relaxation. The pathogens including adenovirus, Bordetella pertussis, parainfluenza 2 and parainfluenza 4 showed increased positivity predominantly in children aged under 10 years. Conversely, some pathogens including human metapneumovirus, rhinovirus/enterovirus, and respiratory virus (RSV) increased in broad range of age groups. SARS‐CoV‐2 positivity rates decreased in children under 10 years but increased in those aged over 60 years. Discussion: Age‐stratified analysis reveals a dynamic pattern of circulating pathogen in each age group after relaxation measures. This study provides essential epidemiologic data that can guide strategies to protect different age groups and effectively respond to respiratory infections in post‐COVID‐19 era. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) can cause severe disease among infants and older adults. Less is known about RSV among pregnant women. Methods To analyze hospitalizations with laboratory-confirmed RSV among women aged 18 to 49 years, we used data from the RSV Hospitalization Surveillance Network (RSV-NET), a multistate population-based surveillance system. Specifically, we compared characteristics and outcomes among (1) pregnant and nonpregnant women during the pre–COVID-19 pandemic period (2014–2018), (2) pregnant women with respiratory symptoms during the prepandemic and pandemic periods (2021–2023), and (3) pregnant women with and without respiratory symptoms in the pandemic period. Using multivariable logistic regression, we examined whether pregnancy was a risk factor for severe outcomes (intensive care unit admission or in-hospital death) among women aged 18 to 49 years who were hospitalized with RSV prepandemic. Results Prepandemic, 387 women aged 18 to 49 years were hospitalized with RSV. Of those, 350 (90.4%) had respiratory symptoms, among whom 33 (9.4%) were pregnant. Five (15.2%) pregnant women and 74 (23.3%) nonpregnant women were admitted to the intensive care unit; no pregnant women and 5 (1.6%) nonpregnant women died. Among 279 hospitalized pregnant women, 41 were identified prepandemic and 238 during the pandemic: 80.5% and 35.3% had respiratory symptoms, respectively (P <.001). Pregnant women were more likely to deliver during their RSV-associated hospitalization during the pandemic vs the prepandemic period (73.1% vs 43.9%, P <.001). Conclusions Few pregnant women had severe RSV disease, and pregnancy was not a risk factor for a severe outcome. More asymptomatic pregnant women were identified during the pandemic, likely due to changes in testing practices for RSV. [ABSTRACT FROM AUTHOR]

Background. The impact of SARS-CoV-2 infection alongside with influenza and RSV, the major viral agents in pediatric disordes, may be an important concern to the healthcare system. Clinical outcomes of the interaction are unknown. The aim of this systematic review is to contribute at establishing the prevalence of the co-infection, its clinical outcomes and potential risk factors. Methods. A systematical literature search was performed for papers published in PubMed, Scopus, Web of Science, Pedro and Cochrane Library, from January 2020 - the beginning of the COVID 19 pandemic - to June 2023. Our review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methods. Studies were eligible for inclusion if they approached the co-infection COVID 19 and influenza or RSV, and were available in English. Due to the fact that studies conducted on pediatric population are scarce, we included patients of all ages. Results. Out of 159 articles found, 12 were eligible for inclusion. The prevalence of co-infection was between 5% and 12 % for influenza viruses and 10% for RSV. The most common symptoms were high-grade fever, cough, headache, and shortness of breath and the most frequent complications were pneumonia and respir-atory distress. In terms of laboratory findings, co-infected patients presented with signifi-cant lymphopenia and pronounced inflammatory response, as well as a progressive ten-dency towards pneumonia and respiratory distress. Regarding the clinical outcomes of co-infection, the majority of articles indicated that simultaneous infection with SARS-CoV-2 and influenza predisposes to a more severe course of the disease(s), with a longer length of hospital stay and an increased risk of death. Conclusion. Our study underlines that the frequency of such co-infections, although not very high, predisposes to more frequent hos-pitalisations and a longer length of stay, complications including admission to intensive care and more severe outcomes, including life-threatening events. It is therefore essential to determine the epidemiological impact of such an interaction nowadays, in order to in-form and adjust treatment and control and prevention strategies, for limiting co-infection between major respiratory viruses. Due to the lack of studies on children, we were unable to identify specific features of co-infections in this population. Therefore, more studies are needed to evaluate the paediatric population and consequently, our doctoral research en-deavour is warranted. [ABSTRACT FROM AUTHOR]

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life. NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function. [ABSTRACT FROM AUTHOR]

Introduction: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children. Methods: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics. Results: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups. Conclusion: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory illness (LRI) and a vaccine for immunization of children is needed. RSV/6120/ΔNS2/1030s is a cDNA-derived live-vaccine candidate attenuated by deletion of the interferon antagonist NS2 gene and the genetically stabilized 1030s missense polymerase mutation in the polymerase, conferring temperature sensitivity. Methods A single intranasal dose of RSV/6120/ΔNS2/1030s was evaluated in a double-blind, placebo-controlled trial (vaccine to placebo ratio, 2:1) at 105.7 plaque-forming units (PFU) in 15 RSV-seropositive 12- to 59-month-old children, and at 105 PFU in 30 RSV-seronegative 6- to 24-month-old children. Results RSV/6120/ΔNS2/1030s infected 100% of RSV-seronegative vaccinees and was immunogenic (geometric mean RSV plaque-reduction neutralizing antibody titer [RSV-PRNT], 1:91) and genetically stable. Mild rhinorrhea was detected more frequently in vaccinees (18/20 vaccinees vs 4/10 placebo recipients, P =.007), and LRI occurred in 1 vaccinee during a period when only vaccine virus was detected. Following the RSV season, 5 of 16 vaccinees had ≥4-fold rises in RSV-PRNT with significantly higher titers than 4 of 10 placebo recipients with rises (1:1992 vs 1:274, P =.02). Thus, RSV/6120/ΔNS2/1030s primed for substantial anamnestic neutralizing antibody responses following naturally acquired RSV infection. Conclusions RSV/6120/ΔNS2/1030s is immunogenic and genetically stable in RSV-seronegative children, but the frequency of rhinorrhea in vaccinees exceeded that in placebo recipients. Clinical Trials Registration NCT03387137. [ABSTRACT FROM AUTHOR]

Background Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care. Objective To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children. Methods We searched Ovid MEDLINE and EMBASE for published clinical studies that investigated outcomes of palivizumab use in children. We included clinical trials, cohort studies, and case–control studies. The primary outcomes were RSV-related or respiratory viral infection-related hospitalizations, or RSV-related mortality. This systematic review was registered in PROSPERO (ID CRD42021248619) and is reported in accordance with the PRISMA guidelines. Results From the 1993 records, six studies were eligible and included, for a total of 625 immunocompromised children with an heterogeneous composition of primary and acquired immunodeficiencies enrolled from palivizumab programs. There were no intervention studies. None of the studies included a control group. RSV hospitalizations were infrequent (0%–3.1% of children). Most children included received palivizumab, although one study (n  = 56) did not specify how many received palivizumab. RSV mortality was neither observed, in three studies, nor reported, in three other studies. Conclusions The evidence supporting the use of palivizumab for prevention of severe RSV disease in immunocompromised children remains extremely limited and appears insufficient to justify prioritizing this intervention as the current standard of care over alternative interventions. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection is associated with significant morbidity in infants. Risk factors for severe disease beyond the first 2 years of life have not been fully defined. Methods: Children <5 years hospitalized with virologically confirmed RSV infection were identified over six respiratory seasons (10/2012–4/2018) and their medical records manually reviewed. Multivariable analyses were performed to define the age‐specific (<6, 6–24, and >24–59 months) risk factors associated with oxygen administration, PICU admission, mechanical ventilation, and duration of hospitalization. Results: We identified 5143 children hospitalized with RSV infection: 53.5% (n = 2749) <6 months; 31.7% (n = 1631) 6–24 months; and 14.8% (n = 763) >24–59 months. Rates of ICU admission were high (35%–36%) and comparable across age groups, while children >24–59 and 6–24 versus those <6 months required supplemental oxygen more frequently (73%; 71%; 68%, respectively; p =.003). The presence of comorbidities increased with age (25%, <6 months; 46%, 6–24 months; 70%, >24–59 months; p <.001). Specifically, neuromuscular disorders, chronic lung disease, and reactive airway disease/asthma were predictive of worse clinical outcomes in children aged 6–24 and >24–59 months, while RSV‐viral codetections increased the risk of severe outcomes in children aged <6 and 6–24 months of age. Conclusions: Almost half of children hospitalized with RSV infection were >6 months. Underlying comorbidities increased with age and remained associated with severe disease in older children, while RSV‐viral codetections were predictive of worse clinical outcomes in the youngest age groups. These data suggest the importance of defining the clinical phenotype associated with severe RSV according to age, and the persistent burden associated with RSV beyond infancy. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post–ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post–dose 2. Conclusions ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration.  NCT03636906. [ABSTRACT FROM AUTHOR]

Background Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest"). Methods Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups. Results In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without. Conclusions RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease. Clinical Trials Registration ClinicalTrials.gov: NCT04886596. [ABSTRACT FROM AUTHOR]

The approval of nirsevimab brings light to reducing the heavy disease burden caused by respiratory syncytial virus (RSV). Considering the seasonality of RSV, the timing of administrating monoclonal antibody (mAb) is critical to maximize health utility. This study aimed to model and seek the optimal seasonal mAb administration strategy for preventing RSV-associated hospitalization. Age-season specific hospitalization rates for RSV-associated acute lower respiratory infection (RSV-ALRI) were estimated from a hospital-based birth cohort. Using these rates, we simulated and evaluated the effect of diverse mAb administration strategies on preventing RSV-ALRI hospitalization. Optimal strategies were selected based on their effectiveness and relative cost-effectiveness. Compared with the year-round strategy of administration mAb at birth for all children, 291 out of the 854 candidate strategies, featuring diverse administration timing and age thresholds, demonstrated a greater number of averted RSV-ALRI hospitalizations and a lower number needed to treat (NNT). The NNT represents the number of mAb doses needed to prevent one case of RSV-ALRI hospitalization. Among the 291 strategies, administration mAb to children born in July-January or August-January at birth and administrating to the remaining <12 months old children in September, exhibited the highest increase in averted RSV-ALRI hospitalizations than the year-round strategy, with a magnitude of 23 %, while also achieve an 18 % reduction in NNT. Administrating monoclonal antibodies to children born in July to January at birth, and administrating to the remaining <1-year-old children in September or October would be the optimal seasonal mAb administration strategy for children in Suzhou, China. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children worldwide. RSV-associated deaths in children are underreported in Bangladesh. We analyzed hospital-based surveillance data on severe acute respiratory infections (SARIs) in under-five children before (August 2009–February 2020) and during the COVID-19 pandemic (March 2020–March 2022). Using the World Health Organization definition, we identified SARI cases in 14 tertiary-level hospitals. Nasopharyngeal and oropharyngeal swabs were collected for real-time reverse-transcriptase–polymerase chain reaction (rRT-PCR) testing of six respiratory viruses, including RSV. SARI deaths during the pandemic (2.6%, 66) were higher than pre-pandemic (1.8%, 159; p < 0.001). Nearly half of pandemic deaths (47%) had underlying respiratory viruses, similar to the pre-pandemic rate (45%). RSV detection in deaths was consistent pre-pandemic (13%, 20/159) and during the pandemic (12%, 8/66). Children aged < 6 months constituted 57% (16) of RSV-related deaths. Evaluating interventions like maternal vaccination and infant monoclonal antibody prophylaxis is crucial to address RSV, a major contributor to under-five SARI deaths. [ABSTRACT FROM AUTHOR]

Infants are a unique pediatric group due to their high hospitalization rates and unfavorable outcomes from acute infectious diseases. Understanding the clinical differences and aftereffects of SARS-CoV-2 in comparison to other prevalent viruses in this age group, like RSV, is crucial for effective management. We conducted a retrospective case–control study of infants hospitalized with SARS-CoV-2 or respiratory syncytial virus (RSV) infection in one year, in a tertiary pediatric hospital in Bucharest, Romania. A total of 188 infants were included in the analysis in a 1:1 ratio (94 with SARS-CoV-2 infection and 94 with RSV infection). Infants with COVID-19 were 10.2 times more likely to have fever (p < 0.001) and 2.4 times more likely to have diarrhea (p = 0.016). Conversely, infants with RSV were 2.5 times more likely to have a cough (p < 0.001), 3.0 times more likely to have nasal congestion (p < 0.001), and 14.7 times more likely to present with dyspnea (p < 0.001). Increased lymphocyte count was more common in infants with RSV (p = 0.008), while lymphopenia was more frequent in infants with SARS-CoV-2 (p = 0.011). The median length of hospital stay was one day longer in infants with RSV infection (5 days vs. 4 days). Overall, infants with RSV infection had a 27.3-fold increased risk of developing respiratory failure (p < 0.001), while infants with COVID-19 had a 5.8-fold increased risk of laryngitis (p = 0.003). Our findings suggest that infants with SARS-CoV-2 infection may present with polymorphic symptoms, mostly dominated by fever, whereas infants with RSV often present with respiratory symptoms. Laboratory differentiation between the two infections is challenging; therefore, the use of rapid antigen or molecular diagnostic tests is crucial for accurate diagnosis, epidemiologically appropriate measures, and effective management. Continued surveillance of both viruses in infants, and beyond, and the implementation of specific control measures are needed to mitigate their impact on this vulnerable pediatric group. [ABSTRACT FROM AUTHOR]

Background In autumn 2022, the epidemics due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza overlapped, and these diseases can present with the same symptomatology. The use of a triple antigen test (SARS-CoV-2 + influenza A/B + RSV) seems crucial for accurate viral diagnosis in the context of implementing long-acting monoclonal antibody vaccination against RSV in the upcoming RSV season. Methods We assessed the usefulness of the triple test in real life in this prospective study performed from October 2022 to May 2023 and involving 116 pediatricians (2 emergency department pediatricians and 114 ambulatory pediatricians). Children <15 years old with flu-like illness (with fever), bronchiolitis (dyspnea ± wheezing), otitis, and croup were enrolled and sampled with a nasal triple test. Results For 8329 children with flu-like illness (65.3%), bronchiolitis (17.9%), otitis (8.8%), and croup (6.3%), the use of the triple test led to a viral diagnosis in 47.9% of cases. The highest RSV positivity occurred in children with bronchiolitis (32.9%). The highest influenza A and B positivity (24.6% and 19.6%) occurred in children with flu-like illness. A succession of 3 epidemics (RSV and influenza A and B) occurred over time with several overlap periods. Conclusions The triple test allowed for a viral diagnosis in half of our cases. The upcoming introduction of RSV prevention will emphasize the need for active surveillance with viral results both in ambulatory settings and hospitals. Clinical Trials Registration. NCT0441231. [ABSTRACT FROM AUTHOR]

The aim of this work is to analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two-antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection. [ABSTRACT FROM AUTHOR]

Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1‐like protein 3 (ORMDL3) and lead to NOD‐like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV‐induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12‐SV40 2B (BEAS‐2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV‐bronchiolitis follow‐up. In BEAS‐2B, ORMDL3‐induced NLRP3 inflammasome expression. BEAS‐2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3‐small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression. [ABSTRACT FROM AUTHOR]

Studies have linked respiratory syncytial virus (RSV) antibody-mediated phagocytosis and complement deposition to severe RSV infection in humans. This study shows waning of these antibody functions in women of childbearing age in 2020-2021 during the implementation of COVID-19 mitigation measures, in absence of RSV circulation. These functions could be explored as correlates of protection against severe RSV disease. [ABSTRACT FROM AUTHOR]

This study examined attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya. First pregnancy was associated with higher vaccine hesitancy among pregnant and lactating people, and social norms were associated with higher vaccine hesitancy among lactating people. Understanding maternal RSV attitudes is critical for vaccine acceptance. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. Since the beginning of the COVID-19 pandemic, non-pharmacological interventions were applied, interfering with the circulation of most respiratory viruses, including RSV. The aim of this study is to analyze the RSV infection trend among hospitalized infants during the actual epidemic season (2022–2023) in comparison with the last pre-pandemic season (2018–2019), in order to outline whether significant differences emerge due to COVID-19 pandemia. We retrospectively reviewed medical data on infants hospitalized at the Bambino Gesù Children's Hospital with diagnosis of bronchiolitis in the current epidemic season and in the last pre-pandemic season, 2018–2019. RSV remains the main etiological agent of bronchiolitis in terms of frequency and severity of infections in the ongoing epidemic season. The first RSV case of the 2022–2023 season was detected at week 42 vs week 47 in the 2018–2019 season. The length of epidemic season was of 17 weeks in 2022–2023 vs 18 weeks in 2018–2019. Comparing the two seasons, age at admission was significantly higher in the current season (median age 2022–2023 65 days vs median age 2018–2019 58 days), but the disease severity was similar. Conclusions: The 2022–2023 bronchiolitis season in Italy started earlier than the usual pre-pandemic seasons but seasonality pattern may be going back to the pre-pandemic one. This season was not more severe than the previous ones. The impact of RSV disease on health care systems and costs remains a critical issue. What is Known: • RSV is one of the major leading causes of hospitalization among children aged less than 3 months. SarsCOV2 pandemic interfered with the seasonal circulation of most respiratory viruses, Including RSV. What is New: • The 2022–2023 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons but seasonality pattern may be realigning to the pre-pandemic one. The impact of RSV disease on health care systems and costs is concerning. [ABSTRACT FROM AUTHOR]

Identifying and understanding genetic factors that influence the propagation of the human respiratory syncytial virus (RSV) can lead to health benefits and possibly augment recent vaccine approaches. We previously identified a p53/immune axis in which the tumor suppressor p53 directly regulates the expression of immune system genes, including the seven members of the APOBEC3 family of DNA cytidine deaminases (A3), which are innate immune sentinels against viral infections. Here, we examined the potential p53 and A3 influence in RSV infection, as well as the overall p53-dependent cellular and p53/immune axis responses to infection. Using a paired p53 model system of p53+ and p53- human lung tumor cells, we found that RSV infection activates p53, leading to the altered p53-dependent expression of A3D, A3F, and A3G, along with p53 site-specific binding. Focusing on A3G because of its 10-fold-greater p53 responsiveness to RSV, the overexpression of A3G can reduce RSV viral replication and syncytial formation. We also observed that RSV-infected cells undergo p53-dependent apoptosis. The study was expanded to globally address at the transcriptional level the p53/immune axis response to RSV. Nearly 100 genes can be directly targeted by the p53/immune axis during RSV infection based on our p53BAER analysis (Binding And Expression Resource). Overall, we identify A3G as a potential p53-responsive restriction factor in RSV infection. These findings have significant implications for RSV clinical and therapeutic studies and other p53-influenced viral infections, including using p53 adjuvants to boost the response of A3 genes. [ABSTRACT FROM AUTHOR]