Search Results (1,050)

Background: Bronchiolitis, due to respiratory syncytial virus, is the most common cause of hospitalization and lower respiratory tract infections in infants and toddlers across the globe. Data on RSV epidemiology in Romania are limited and are mainly derived from national surveillance systems. Understanding regional trends in RSV bronchiolitis, its etiology, and its severity is important while assessing the potential impacts of future prevention measures. Methods: We conducted a retrospective cohort study including infants hospitalized with bronchiolitis between 2019 and 2023 in a tertiary pediatric center in Central Romania. Demographic, clinical, and treatment data were analyzed. Comparative analyses between RSV-positive and RSV-negative cases were performed among patients tested for RSV. Disease severity was assessed using oxygen saturation at admission and length of hospital stay. Results: A total of 2967 bronchiolitis hospitalizations were identified during the study period. After exclusion of 167 cases due to hospitalization <24 h or incomplete medical records, 2800 patients were included in the final analysis. The number of admissions decreased in 2020 (n = 301) compared to 2019 (n = 638), followed by an increase in 2021 (n = 463) and a peak in 2022 (n = 745), with a slight decrease in 2023 (n = 653). Among tested patients, RSV positivity increased from 14.4% in 2019 to 37.7% in 2022, then decreased to 27.4% in 2023. RSV-positive cases were more frequent in younger age groups, particularly those under 6 months of age. Compared to RSV-negative cases, RSV-positive bronchiolitis was associated with lower oxygen saturation at admission, and a longer hospital stay (<0.001), indicating a more severe clinical course. Treatment differences were also observed, with higher use of corticosteroids in RSV-positive patients (p < 0.002), while antibiotic use was similar between groups (p = 0.149). Conclusions: RSV infection was associated with a more severe clinical course in our cohort and continues to play a central role in the burden of disease. The variability observed in treatment practices also suggests that further efforts are needed to better align clinical management with current evidence-based recommendations. Full article

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children, but predictors of critical illness remain poorly defined. This study aimed to identify risk factors for critical RSV pneumonia and develop a predictive model. Methods: A retrospective analysis of 12,035 children hospitalized with RSV infection between 2019 and 2025 identified 304 eligible patients after applying exclusion criteria. Among these, 30 children with critical illness and 90 randomly selected non-critical controls were included. Clinical characteristics, laboratory parameters, and co-infection patterns were compared. Univariate, Lasso, and multivariable logistic regression analyses were performed to identify independent predictors, which were then incorporated into a nomogram. Model performance was assessed using the ROC curve, calibration plot, and decision curve analysis. Results: Among the 304 eligible children, 30 (9.9%) developed critical illness. Co-infection with three or more pathogens was most frequent in the critical group (43.3%), whereas single RSV infection predominated in the non-critical group (38.9%). Multivariable logistic regression identified four independent predictors of critical illness: interleukin-6 (IL-6), creatine kinase-MB (CK-MB), serum bilirubin excretion (SBE), and neutrophil percentage. The nomogram combining these factors exhibited excellent discrimination (AUC = 0.921, 95% CI: 0.868–0.974). The calibration curve closely matched the ideal 45° reference line (Hosmer–Lemeshow χ² = 3.233, p = 0.919), and decision curve analysis demonstrated clinical benefit across threshold probabilities ranging from 0.01 to 0.99. Conclusions: Elevated IL-6, CK-MB, neutrophil percentage, and SBE are independent predictors of critical RSV infection in children. The nomogram based on these accessible biomarkers provides a robust tool for early risk assessment and guiding clinical decisions. Full article

Background/Objectives: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus type 3 (PIV3) are leading causes of acute respiratory infections in children and the elderly, yet no licensed T-cell vaccines are available. This study aimed to develop multivalent T-cell vaccine candidates against these pathogens using a live attenuated influenza virus (LAIV) vector platform. Methods: Conserved F, N, and M proteins of RSV, hMPV, and PIV3 were identified through multiple sequence alignments. Fragments enriched with experimentally confirmed and predicted T-cell epitopes were selected using the IEDB and NetMHCpan servers. These fragments were assembled into polyepitope immunogenic cassettes, and their selected order was determined by thermodynamic analysis of mRNA secondary structures using the RNAfold Web Server. The selected cassettes were cloned into the neuraminidase (NA) gene of a cold-adapted LAIV vector. Recombinant viruses were rescued by reverse genetics and assessed for replicative fitness in embryonated chicken eggs and MDCK cells, NA enzymatic activity and genetic stability upon serial passaging. Results: Four cassettes were designed for RSV, three for hMPV, and one for PIV3, all containing fragments with multiple T-cell epitopes. Three recombinant viruses of LAIV/RSV type and three of LAIV/hMPV type were successfully rescued, while attempts to recover the remaining recombinant viruses, i.e., LAIV/RSV and LAIV/PIV3, were not successful. All rescued recombinant viruses replicated to titers comparable to the parental LAIV strain and retained the full-length insert for at least eight passages in eggs. Importantly, NA enzymatic activity of the LAIV vector was not compromised by the insertion of the polyepitope T-cell cassettes. Conclusions: We developed a panel of recombinant T cell-based vaccine candidates against RSV and hMPV using the LAIV vector platform. These recombinant viruses encode conserved T-cell epitopes of the target viruses while retaining the biological properties of LAIV strains. Taken together, these characteristics warrant further evaluation of these recombinant viruses in appropriate relevant in vitro models to directly assess their immunogenicity in terms of stimulating a T-cell response against target pathogens. Full article

We aimed to characterize age-stratified C-reactive protein (CRP) patterns across respiratory virus infections, assess age-related CRP shifts in virus-not-detected-by-PCR episodes, and evaluate the independent associations of age and virus type with CRP levels. We retrospectively analyzed 19,002 test-level episodes with paired respiratory PCR and serum CRP results from a single tertiary-care center between 2008 and 2024. Episodes were classified as virus-not-detected-by-PCR or virus-positive according to multiplex PCR results; the former was not considered a healthy control and may include off-panel infections, bacterial/mixed infections, false-negative results, or non-infectious inflammation. Descriptive analyses and multivariable linear regression of log-transformed CRP were used to assess adjusted associations. Median CRP increased with age in both virus-positive and virus-not-detected-by-PCR episodes, rising from 0.38 to 7.42 mg/dL across age groups in the latter. Age showed the strongest association with CRP. Adenovirus showed a positive adjusted association, whereas influenza A/B, respiratory syncytial virus A/B, and parainfluenza virus types 1 and 3 showed selective negative associations. Overall, CRP variation was more strongly associated with age-related clinical background than with virus type, although selective virus-associated differences were observed, supporting the interpretation of CRP as a non-specific, composite host-response indicator within broader clinical contexts. Full article

Background: Respiratory syncytial virus (RSV) is a serious disease in older adults and is associated with various comorbidities; however, comparative data across epidemic waves, both clinically and in terms of inflammatory profiles and their diagnostic and prognostic utility, remain limited. Methods: We conducted a retrospective study of adults hospitalized with RSV infection across two epidemic waves (2022–2023 and 2024–2025). Data on clinical characteristics, comorbidities, severity scores, and outcomes were collected, and serum interleukin-6 (IL-6), C-reactive protein (CRP), and hematological parameters were analyzed and compared with those in healthy controls. Results: A total of 152 patients were included in this study (81 in wave 1 and 71 in wave 2). Patients in wave 2 were older and had a higher burden of comorbidities, although ICU admission and in-hospital mortality were similar across waves. RSV induced a consistent systemic inflammatory response in both waves, characterized by elevated IL-6 and CRP levels, neutrophilia, lymphopenia, and increased neutrophil-to-lymphocyte ratios, with no relevant inter-wave differences. All biomarkers demonstrated good diagnostic performance. The neutrophil-to-lymphocyte ratio showed the highest accuracy, while IL-6 exhibited high rule-in capacity. However, none of the evaluated biomarkers were associated with disease severity or mortality. Conclusion: RSV infection in older adults is associated with a similar inflammatory profile across waves. Although biomarkers showed strong diagnostic utility, they did not show any significant prognostic discrimination in this cohort. We suggest that disease severity is primarily associated with host-related factors, particularly comorbidities, rather than with differences in the inflammatory response, highlighting the need for improved preventive and risk-stratification strategies in this population. Full article

Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. Results: JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-γ (IFN-γ) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including Gemella, Sutterella, and CC_115, and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. Conclusions: JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite–microbiota interactions underlying the anti-RSV activity of JYH. Full article

Background/Objectives: Respiratory tract infections (RTIs) are a leading cause of morbidity in children under five, with over 75% experiencing recurrent episodes and an increased risk of asthma by school age, particularly following respiratory syncytial virus (RSV) and rhinovirus (RV) infections. While current therapies primarily address acute symptoms, effective preventive strategies remain limited. Bacterial-derived immunomodulators have emerged as promising interventions, but their mechanisms and pediatric clinical evidence remain incompletely characterized. This narrative review examines preclinical mechanisms and clinical findings for four such agents, contextualizing current evidence and identifying key gaps. Methods: A targeted narrative review of PubMed-indexed literature (inception to September 2025) was conducted. Mechanistic studies, pediatric (0–18 years) clinical trials, and meta-analyses evaluating OM-85, polyvalent mechanical bacterial lysates (PMBL/Ismigen), MV130, and Lactobacillus rhamnosus CRL1505 were included. Outcomes of interest comprised immunological mechanisms, RTI incidence, wheezing, and asthma-related outcomes. Results: All four agents share convergent immunomodulatory mechanisms involving epithelial barrier reinforcement, innate immune activation, and adaptive immune modulation. OM-85 has the most extensive preclinical evidence. PMBL enhances epithelial repair via the IL-23/IL-22 axis, MV130 induces trained immunity, and CRL1505 acts through the gut–lung axis. Clinical evidence varies markedly, with OM-85 showing the most comprehensive data (18 RCTs and 7 meta-analyses), followed by PMBL and MV130, while evidence for CRL1505 remains predominantly preclinical. Conclusions: Despite variable evidence maturity, these agents share a coherent mechanistic rationale and favorable safety profiles, with ongoing studies expected to clarify their clinical role in early-life respiratory prevention. Full article

Background/Objectives: Respiratory syncytial virus (RSV) is the leading cause of infant hospitalizations in the United States. Prevention strategies are recommended to mitigate severe RSV outcomes. In addition to identifying potential coverage gaps, preventative administration timing is important for estimating product effectiveness. This study characterized administration timing of maternal and infant immunization against RSV across the United States during the 2024–2025 RSV season. Methods: A retrospective cross-sectional study was conducted using administrative claims of a commercially insured population from Kythera Labs. Pregnant individuals who received RSVpreF vaccine and infants who received nirsevimab were included. The seasonal cohort included infants born during the RSV season, while infants born from April to September were considered as the catch-up cohort. Baseline characteristics and calendar month and age at immunization (gestational age for RSVpreF) were evaluated. Results: Overall, 37,686 (71.9%) of maternal vaccinations were administered at 32–34 gestational weeks and 92.7% of all vaccinations occurred ≥14 days before delivery. Among infants who received nirsevimab, 34.8% of the seasonal cohort were immunized within 1 week of birth and 33.4% of the catch-up cohort were immunized in October 2024. Conclusions: Most maternal RSVpreF vaccinations occurred early in the recommended eligible gestational age window, while only approximately one-third of infants received nirsevimab during the first week of life or at the beginning of the RSV season. These findings highlight the importance of timely administration of RSV preventives. They further demonstrate that immunization timing should be incorporated into evaluation of the effectiveness and population level impact of RSV prevention programs. Full article

Background/Objectives: Marine-derived bioactive compounds have attracted increasing interest due to their potential antiviral properties. This study investigated in vitro antiviral activity of oil extracted from the green-lipped mussel (Perna canaliculus, GLM) and low-molecular-weight (LMW) fucoidan from Undaria pinnatifida against three human viruses in mammalian cell systems. herpes simplex virus-1 (HSV-1), respiratory syncytial virus (RSV), and SARS-CoV-2. These marine compounds were selected with the longer-term aim of evaluating their combination as a potential synergistic antiviral strategy. Methods: Antiviral efficacy was assessed using complementary assay platforms, including plaque reduction assays in mammalian cell systems and a lentiviral pseudovirus system delivering a bioluminescent reporter gene in HEK293/ACE2 cells pseudotyped with the SARS-CoV-2 spike glycoprotein. Cytotoxicity was assessed in parallel, and the selectivity index (SI) was calculated as the ratio of CC₅₀ to IC₅₀ for each compound and virus tested. Results: GLM oil showed potential antiviral activity against SARS-CoV-2 pseudovirus (SI > 6.20), with limited activity against RSV (SI > 3.48) and HSV-1 (SI > 2.28). In contrast, LMW fucoidan did not demonstrate antiviral activity against any of the tested viruses. Conclusions: These findings support further investigation of GLM-derived bioactive compounds as potential antiviral agents, including studies to elucidate their mechanisms of action and in vivo studies to confirm their antiviral efficacy. Combination studies were not pursued in the present work as both compounds require further optimisation individually; however, future studies should evaluate their combined antiviral potential, as synergistic or additive effects remain plausible. Full article

Background/Objective: Respiratory syncytial virus (RSV) is an often under-recognized cause of respiratory illness in older adults. Clinical overlap with bacterial infections and delayed virologic confirmation may lead to the unnecessary prescription of antibiotics and antimicrobial resistance (AMR). This systematic review was conducted to assess antibiotic prescription in older adults with RSV and the factors influencing these decisions. Methods: This systematic review was preregistered in PROSPERO (CRD42024586905) and reported according to PRISMA guidelines. PubMed/MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and Scopus were searched for studies published between January 2000 and August 2025. Eligible studies were those including adults aged ≥60 or ≥65 years with RSV infection and reporting antibiotic use. Data on antibiotic prescription, confirmed bacterial infection, hospitalization, length of stay (LOS), and prescribing indications were extracted. Results: Eight observational studies across inpatient, outpatient, emergency, and primary-care settings were included. Antibiotic prescribing ranged from 40.0% to 97.7%, whereas confirmed bacterial infection did not exceed 20% in any study. Antibiotic prescribing was associated with diagnostic uncertainty, radiologic findings, inflammatory markers, respiratory distress, delayed RSV testing, and multimorbidity rather than microbiological confirmation. Hospitalization rates varied across settings, and the LOS ranged from 3.5 to 11 days. None of the studies reported antibiotic discontinuation following RSV confirmation. Conclusions: Older adults with RSV frequently receive antibiotics despite low rates of confirmed bacterial infection, indicating substantial empirical prescribing. Improved rapid diagnostics, reassessment of therapy, and strengthened antimicrobial stewardship may help reduce unnecessary antibiotic use. RSV vaccination may be a promising strategy for reducing severe disease and hospitalization, with a potential indirect effect on antibiotic use, although these effects remain hypothetical. Full article

The coronavirus disease pandemic impacted respiratory virus circulation and seasonality, but its effect on viral co-detection patterns remains unclear. We examined temporal changes in co-detection burden and dominant pairwise patterns across pandemic periods. We analyzed 23,284 respiratory virus multiplex PCR tests performed at a tertiary care center in the Republic of Korea from 2007 to 2024. Co-detection was defined as detection of ≥2 viruses in a single episode. To address temporal panel changes, we used crude full-panel, restricted 12-target, and recent-period sensitivity analyses based on a stable respiratory virus target set. Co-detection burden showed discordant trends across analytical approaches. In the crude analysis, co-detection among positive episodes was the highest during the pandemic. In the restricted analysis, co-detection decreased from 20.5% before to 14.8% during and 12.2% after the pandemic. Pairwise co-detection patterns also shifted: adenovirus–rhinovirus predominated before the pandemic, whereas rhinovirus-containing pairs involving parainfluenza virus type 3 or respiratory syncytial virus B accounted for relatively larger shares during and, to a lesser extent, after the pandemic. These findings suggest that post-pandemic respiratory virus surveillance should consider not only single-virus positivity or overall co-detection frequency, but also the composition of dominant pairwise viral combinations captured by multiplex PCR. Full article

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants, older adults, and immunocompromised individuals. Over the past decade, advances in structural biology, particularly cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), have transformed our understanding of RSV architecture, dynamics, and the mechanisms of entry and replication. High-resolution structures of the prefusion F glycoprotein (pre-F) and its complexes with neutralizing antibodies established the rationale for structure-guided antigen stabilization and directly enabled the development of the first licensed RSV vaccines. Complementary structures of the ribonucleoprotein, polymerase complex, and matrix lattice have broadened therapeutic targets beyond F. Here, we summarize these structural advances; review current structure-guided vaccine, antibody, and antiviral development efforts; and highlight priorities for next-generation vaccines and therapeutics. Full article

Influenza sentinel surveillance in Libya was formally established in 2022 by the Libyan National Center for Disease Control (NCDC). Between 2022 and 2024, a total of 1864 nasopharyngeal specimens were collected from patients presenting with influenza-like illness and tested using the GeneXpert for influenza A virus, influenza B virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV). Influenza A virus was detected in 21.1% (393/1864) of samples and influenza B virus was detected in 5.4% of samples (100/1864). SARS-CoV-2 and RSV were identified in 11.6% (216/1864) and 4.1% (77/1864) of specimens, respectively. A subset of 22 influenza A-positive samples was selected based on sample availability and sufficient remaining volume after the initial test for confirmatory testing and further molecular characterization. Real-time RT-PCR subtyping identified 11 A(H1N1)pdm09 and four A(H3N2) viruses. Whole-genome sequencing was successfully performed for 11 isolates, followed by phylogenetic analysis. Genetic characterization revealed that all A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.2a (5a.2a), while A(H3N2) viruses clustered within clade 3C.2a1b.2a.2a.3a.1 (2a.3a.1) were based on hemagglutinin gene mutations. No neuraminidase mutations associated with antiviral resistance were detected. This study represents the first molecular and phylogenetic characterization of circulating human influenza viruses in Libya, with sequence data submitted to the Global Initiative on Sharing All Influenza Data (GISAID) to establish baseline genetic data for influenza viruses in Libya. Full article

The objective of this study was to evaluate the effects of timing of injectable trace mineral (ITM) administration (28 days (d) prior to or at weaning) on performance and health in mixed-sex beef calves (n = 115; 224 ± 40 kg). Calves were randomly assigned to one of the following treatments: (1) no ITM (CON), (2) ITM administered 28 d before weaning (PW), or (3) ITM administration at weaning (WEAN). At weaning, calves were transported to a local auction barn, held overnight, and returned the following day; BW, blood, and hair samples were collected prior to and through the receiving period. Data were analyzed using SAS 9.4. Serum Se increased in PW calves following ITM administration (p < 0.01). Serum Mn increased in PW and WEAN groups (p < 0.01) and PW calves showed increased serum Cu at weaning (p < 0.01). Across treatments, calves experienced 6% shrink following weaning and transport, with recovery of BW and intake occurring within 21 d and 8 d, respectively. Despite improved mineral status, no performance benefits were observed during the receiving period, reflecting adequate baseline mineral status and low-stress management conditions, suggesting that ITMs may have limited benefits in well-managed herds. Full article

Introduction. Bronchiolitis is the leading cause of Pediatric Intensive Care Unit (PICU) admission for lower respiratory tract infection in infants. Although survival has improved, concerns remain regarding potential long-term functional impairments, including alterations in psychomotor development, learning, and behavior. This study aimed to describe the epidemiological and clinical characteristics of children admitted to the PICU for bronchiolitis and to evaluate their functional outcomes at 12-month follow-up. Methods. A retrospective descriptive cohort study was conducted, including all patients admitted to the PICU for bronchiolitis during the 2021–2022 period. Epidemiological, clinical, microbiological, and laboratory data were collected. Functional health status was assessed using the Pediatric Overall Performance Category (POPC), Pediatric Cerebral Performance Category (PCPC), and Functional Status Scale (FSS) at PICU discharge and 12 months. Changes in functional status were categorized as improved, stable, or worsened. Exploratory unadjusted analyses were performed to describe differences between outcome groups. Results. A total of 164 patients were included (43.9% female), with a median age of 51 days (IQR 26.25–118.5). Respiratory syncytial virus was identified in 79.7% of cases. Invasive mechanical ventilation was required in 31.1% of patients, and 45.7% developed complications during PICU admission. Mortality was 0.6%. At 12 months, functional deterioration was observed in 14.6% of patients according to POPC, 16.5% according to PCPC, and 3.6% according to FSS. Higher proportions of functional deterioration were observed among patients with underlying medical conditions, those requiring invasive mechanical ventilation, those with complications, and those with longer PICU and hospital stays, particularly in the PCPC scale. Conclusions. Most children admitted to the PICU for bronchiolitis showed stable or improved functional status at 12 months. However, a subset experienced functional deterioration, more frequently observed in patients with greater clinical severity and complexity during admission. These results support the need for further studies to better characterize long-term outcomes and to identify children who may benefit from closer follow-up. Full article