Search Results (650)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC₅₀ = 1.01 mg/mL) compared to Osage orange (EC₅₀ = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article

Background/Objectives: Bronchiolitis is the leading cause of hospitalization in infants under 12 months. While often self-limiting, a subset of cases evolves into severe disease requiring intensive care. This study aimed to identify risk factors for severe bronchiolitis in two consecutive respiratory syncytial virus (RSV) seasons (before and after the introduction of nirsevimab) in Southern Italy. Methods: A retrospective, multicenter cohort study was conducted on all infants ≤12 months hospitalized with bronchiolitis from October 2023 to March 2025. Patients were categorized by disease severity: those requiring Sub-Intensive or Intensive Care (IC group) and others (n-IC group). Demographic and clinical data, virological testing, and therapeutic interventions were analyzed. Multivariable logistic regression was used to identify independent risk factors for severe disease. Results: Among 1056 hospitalized infants, 10.5% required intensive care. RSV was detected in 73.5% of tested patients and was significantly associated with severe outcomes. Independent risk factors for IC admission included younger age (<3 months), comorbidities, and RSV infection. A 33% reduction in bronchiolitis admissions was observed in the second season (post-nirsevimab), although the rate of severe cases remained stable (about 10% in both seasons). Conclusions: Younger age, comorbidities, and RSV infection are significant predictors of severe bronchiolitis. Although overall admissions decreased post-nirsevimab, severe cases persisted. These findings underscore the need for targeted preventive strategies and highlight the potential role of intermediate care approaches in managing bronchiolitis severity. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Artificial intelligence (AI) techniques—ranging from hybrid mechanistic–machine learning (ML) ensembles to gradient-boosted decision trees, support-vector machines, and deep neural networks—are transforming the management of seasonal influenza, respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptom-based triage models using eXtreme Gradient Boosting (XGBoost) and Random Forests, as well as imaging classifiers built on convolutional neural networks (CNNs), have improved diagnostic accuracy across respiratory infections. Transformer-based architectures and social media surveillance pipelines have enabled real-time monitoring of COVID-19. In HIV research, support-vector machines (SVMs), logistic regression, and deep neural network (DNN) frameworks advance viral-protein classification and drug-resistance mapping, accelerating antiviral and vaccine discovery. Despite these successes, persistent challenges remain—data heterogeneity, limited model interpretability, hallucinations in large language models (LLMs), and infrastructure gaps in low-resource settings. We recommend standardized open-access data pipelines and integration of explainable-AI methodologies to ensure safe, equitable deployment of AI-driven interventions in future viral-outbreak responses. Full article

Introduction: Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infections in infants and children, as well as hospitalizations for respiratory infections in the pediatric population, representing a significant public health concern. Nirsevimab, a long-acting anti-RSV monoclonal antibody, has recently been approved by the European Medicines Agency (EMA). The aim of this study is to assess the utility of certain parameters, such as the Number Needed to Immunize (NNI), in supporting decision-makers regarding the introduction of nirsevimab as a universal prophylactic measure. Methods: A literature review was conducted to identify the definition and application of the NNI in the context of infectious disease prevention. The following online databases were consulted: Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library. The search was restricted to English-language texts published between 1 January 2000 and 30 January 2025. Results: The NNI represents the number of individuals who need to be immunized to prevent clinical outcomes such as medical visits and hospitalizations caused by infectious diseases. Six studies were identified that utilized this parameter to outline the benefits of immunization and describe the advantages of using monoclonal antibodies for RSV disease. Finelli and colleagues report that to prevent one RSV-related hospitalization, 37–85 infants aged 0–5 months and 107–280 infants aged 6–11 months would need to be immunized with long-acting anti-RSV antibodies. A recent study by Mallah et al. on the efficacy of nirsevimab estimates that the NNI required to prevent one RSV-related hospitalization is 25 infants. Studies by Francisco and O’Leary report NNI values of 82 and 128 infants, respectively, to prevent one RSV-related hospitalization with nirsevimab. Mallah et al. describe NNI as a metric useful to quantify the immunization effort needed to prevent a single RSV hospitalization. A recent Italian study reports that 35 infants need to be immunized to prevent one hospitalization due to RSV-LRTI and 3 infants need to be immunized to prevent one primary care visit due to RSV-LRTI. The studies indicate that the NNI for anti-RSV monoclonal antibodies is lower than the corresponding Number Needed to Vaccinate (NNV) for vaccines already included in national immunization programs. The main limitations of using this parameter include the absence of a shared threshold for interpreting results and the lack of consideration for the indirect effects of immunization on the population. Conclusions: The NNI is an easily understandable tool that can be used to convey the value of an immunization intervention to a variety of stakeholders, thereby supporting public health decision-making processes when considered in association with the uptake of the preventative strategy. At the current status, the estimated NNI of monoclonal antibodies against RSV results favourable and confirms the use in the first year of life for the prevention of RSV disease. Full article

Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in Tanzania to understand the distribution of respiratory viruses shortly after nonpharmaceutical interventions (NPIs) were lifted. A total of 475 samples that tested negative for SARS-CoV-2 and influenza from March through May 2022 were included in this study. The samples were tested for 16 virus targets using Anyplex II RV16 multiplex assays. The findings indicate that most hospitalizations (74%) were among children under 15 years, with human bocavirus (HBoV) being the most prevalent (26.8%), followed by rhinovirus (RV, 12.3%), parainfluenza viruses (PIVs1–4, 10.2%), respiratory syncytial virus (RSV, 8.7%), adenovirus (AdV, 4.3%), and metapneumovirus (MPV, 2.9%). Notably, 54% of respiratory hospitalizations had no viruses detected. The findings highlight the broad circulation of respiratory viruses shortly after NPIs were lifted in Tanzania. Surveillance for respiratory pathogens beyond influenza and SARS-CoV-2 can inform public health officials of emerging threats in the country and should be considered an important pandemic preparedness measure at a global level. Full article

The COVID-19 pandemic significantly impacted the circulation, seasonality, and disease burden of viral respiratory infections. This study aimed to evaluate the impact of SARS-CoV-2 on the frequency of viral respiratory infections at a teaching hospital in Southern Italy by comparing data from before, during, and after the COVID-19 pandemic and by investigating how the emergence of SARS-CoV-2 affected the circulation and seasonality of other respiratory viruses. This retrospective and prospective study was performed on de-identified nasopharyngeal specimens classified as pre-COVID-19 (before 15 March 2020), during-COVID-19 (from 16 March 2020 to 5 May 2023), and post-COVID-19 (from 6 May 2023 to 31 December 2024). Overall, 790 out of 3930 (20%) patient samples tested positive for at least one respiratory virus. The mean age of patients was 60 ± 19 years, with significant positivity rates observed in the 65–98 age group (p ≤ 0.05) across all periods. In the pre-COVID-19 period, the most prevalent virus was influenza A (47.5%, 47/99), followed by the human rhinovirus (19.2%, 19/99). During the COVID-19 pandemic, SARS-CoV-2 was the most prevalent (64.9%, 290/447), before decreasing to 38% (92/244) after the pandemic, while influenza A’s positivity prevalence increased to 14.3% (35/244). Rhinovirus/enterovirus remained relatively stable throughout all periods. The pandemic notably altered viral co-infection dynamics, with its effects lasting into the post-COVID-19 period. Specifically, a marked decrease in influenza A circulation was observed, while respiratory syncytial virus (RSV) epidemiology remained stable and significant co-circulation of rhinovirus/enterovirus with SARS-CoV-2 persisted. Therefore, since COVID-19 and influenza affect the same high-risk groups, those individuals must be vaccinated against both viruses. Full article

Introduction: Respiratory Syncytial Virus (RSV) infection causes seasonal respiratory illness in both children and adults, with increasing recognition of its impact in older adults with chronic comorbidities. This study aimed to characterize adult patients hospitalized with RSV infection in Switzerland and identify comorbidities linked to poor outcomes. Methods: Adults hospitalized with RSV infection between May 2022 and April 2024 at a Swiss public teaching hospital were included in this retrospective observational study. To assess the association between comorbidities and patient outcomes, separate multivariable regression analyses for each comorbidity, adjusted for age and sex, were performed. The primary composite endpoint was ’severe course’ (in-hospital death or intensive care unit (ICU) admission), secondary endpoints included in-hospital death, ICU admission, and length of stay. Results: Among 136 included patients (mean age 78, 38% male), 98% had comorbidities, most commonly cardiovascular (75.7%), respiratory (51%), and chronic kidney disease (CKD) (36.7%). Further, 18.4% experienced a severe course. The ICU admission rate was 14.0%, in-hospital mortality 6.6%, and the median hospital stay of survivors was 6 days (IQR 4–10). CKD was significantly associated with severe course (OR 2.64, p = 0.045) and in-hospital mortality (OR 11.6, p = 0.025), while immunosuppression predicted ICU admission (OR 5.7, p = 0.018). Length of stay was not linked to any comorbidities. Conclusions: In this cohort of hospitalized adults, mainly elderly individuals with chronic comorbidities were tested positive for RSV. CKD and immunosuppression were associated with severe course. Prevention strategies, including RSV vaccination, should prioritize these high-risk populations. Full article

Background/Objective: Maternal immunization is highly recommended, particularly in developed countries. However, its awareness among pregnant women in Japan remains low. This study aimed to assess the awareness and attitudes toward maternal immunization among pregnant women in Japan and to identify the factors that may promote its acceptance. Methods: We conducted a cross-sectional questionnaire survey among pregnant women attending antenatal checkups at nine facilities in Kanagawa Prefecture, Japan, from August 2024 to January 2025. The survey assessed knowledge and intention regarding maternal immunization for influenza, pertussis, respiratory syncytial virus (RSV), and group B streptococcus (GBS) as well as attitudes toward vaccination costs and information sources. Results: Overall, 523 respondents were included in this study. The overall awareness of maternal immunization was 16%. Willingness to receive vaccinations during pregnancy was reported for influenza (68%), pertussis (58%), RSV (59%), and GBS (71%). A common reason for vaccine hesitancy included uncertainty about its effects on the fetus. The key factors associated with vaccine acceptance were higher educational attainment and prior knowledge of maternal immunization. Regarding costs, most respondents were willing to pay up to JPY 5000 (approximately USD 35). The most frequently prioritized sources were explanations from physicians, followed by explanations from midwives. Conclusions: Despite low awareness, vaccination intention was comparable to that reported in other countries. Points that may contribute to improved vaccine uptake were also identified. These findings may lead to the prevention of infectious diseases in newborns and infants in Japan and possibly improve public health. Full article

Background: Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of lower respiratory tract infections in children under two years of age. NF-κB is a key transcription factor in antiviral and inflammatory responses. This study investigates the expression of NF-κB mRNA in both blood and buccal swab samples of pediatric patients hospitalized for RSV bronchiolitis, comparing levels at admission and discharge. Methods: Paired peripheral blood and buccal swab samples were collected from pediatric patients (n = 85) at hospital admission and discharge. Quantitative real-time PCR was used to assess NF-κB mRNA levels. Results: NF-κB mRNA levels significantly decreased in blood between admission and discharge (p < 0.05), while no significant change was observed in buccal swabs. Conclusions: These results suggest a compartment-specific regulation of NF-κB, with systemic inflammatory resolution at discharge and persistent or distinct mucosal immune activity. Understanding these dynamics may improve our approach to monitoring and treating RSV bronchiolitis. Full article

This study examined whether SNPs at the 17q12-q21 locus that are associated with childhood asthma are also associated with severe respiratory syncytial virus (RSV) infection and viral load. We conducted a candidate SNP association study in the subset of RSV-infected infants who were parent-identified as White (n = 159) in the INSPIRE cohort. Nine SNPs at the 17q12-q21 locus were genotyped. We used an additive model to evaluate each SNP’s association with RSV infection severity and viral load. Replication of significant associations was tested in the TCRI cohort: infants with severe RSV illness. In INSPIRE, an SNP rs8069202-G in the GSDMA gene was associated with increased RSV viral load (and marginally associated with RSV severity). SNP rs2941504, in the PGAP3 gene, was associated with a reduced risk of RSV severity. All significant associations were directionally replicated in the TCRI cohort but were insignificant at a p-value < 0.05. The association of a SNP in GSDMA with RSV viral load and RSV infection severity suggests that GSDMA may be contributing to both severe RSV infection and asthma development. On the other hand, the association between an SNP in PGAP3 and reduced RSV infection severity suggests distinct pathways link PGAP3 to these two respiratory outcomes. Full article

Airborne respiratory viruses (e.g., influenza, respiratory syncytial virus (RSV), and SARS-CoV-2) continue to pose a serious threat to global public health due to their ability to spread through multiple transmission pathways. Among these, aerosol transmission stands out as a key route, particularly in enclosed environments. However, current monitoring systems have major limitations in sensitivity, standardization, and high time resolution. This study provides a summary of the latest information on the monitoring technologies for respiratory virus aerosols. It discusses the technical and ethical challenges in real-world applications. In addition, this study proposes practical solutions and future development pathways. The aim of this study is to provide theoretical support for building a dynamic, precise, and effective early warning system for monitoring variants of airborne respiratory viruses Full article

Background/Objectives: Concurrent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A and B viruses (IAV/IBV), and respiratory syncytial virus (RSV) necessitate rapid and precise differential laboratory diagnostic methods. This study aimed to evaluate the multiplex molecular diagnostic performance of the geneLEAD VIII system (Precision System Science Co., Ltd., Matsudo, Japan), a fully automated sample-to-result precision instrument, in conjunction with the VIASURE SARS-CoV-2, Flu & RSV Real Time PCR Detection Kit (CerTest Biotec, S.L., Zaragoza, Spain). Methods: The specific detection capabilities of SARS-CoV-2, IAV/IBV, and RSV genes were evaluated using virus-spiked saliva and nasal swab samples. Using saliva samples, the viral titer detection limits of geneLEAD/VIASURE and manual referent singleplex RT-qPCR assays were compared. The performance of geneLEAD/VIASURE in analyzing single- and multiple-infection models was scrutinized. The concordance between the geneLEAD/VIASURE and the manual assays was assessed. Results: The geneLEAD/VIASURE successfully detected all the virus genes in the saliva and nasal swab samples despite some differences in the Ct values. The viral titer detection limits in the saliva samples for SARS-CoV-2, IAV, IBV, and RSV using geneLEAD/VIASURE were 10⁰, ≤10⁻², 10⁰, and 10² TCID₅₀/mL, respectively, compared to ≤10⁻¹, ≤10⁰, ≤10⁰, and ≤10⁴ TCID₅₀/mL, respectively, in the manual assays. geneLEAD/VIASURE yielded similar Ct values in the single- and multiple-infection models, with some exceptions noted in the triple-infection models when low titers of RSV were spiked with high titers of the other viruses. The concordance between geneLEAD/VIASURE and the manual assays was high, with Pearson’s R² values of 0.90, 0.85, 0.92, and 0.95 for SARS-CoV-2, IAV, IBV, and RSV, respectively. Conclusions: geneLEAD/VIASURE is a reliable diagnostic tool for detecting SARS-CoV-2, IAV/IBV, and RSV in single- and multiple-infection scenarios. Full article

Macrophages are a principal pulmonary source of type I and III interferons (IFNs), initiating and coordinating the early antiviral response to respiratory viral infections. Yet the contribution of macrophage-derived IFNs to host defense during human metapneumovirus (HMPV) infection remains poorly defined. Here, we use human primary monocyte-derived macrophages (MDMs) and THP-1-derived macrophages to analyze the IFN responses induced by HMPV compared to its closely related human pneumovirus, respiratory syncytial virus (RSV). We show that HMPV induced a robust response of type I and type III IFNs and ISGs, whereas RSV elicited only a modest, delayed IFN response despite strong IRF activation; instead, RSV preferentially activates NF-κB and exhibits a pronounced proinflammatory cytokine output. Our results highlight the role of macrophages as key modulators of the IFN and proinflammatory responses during HMPV and RSV infection. Full article