ABSTRACT Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants, young children, and the elderly. Current licensed prefusogenic F-based RSV vaccines induce systemic immune responses through intramuscular injection. However, mucosal immunization will be required to elicit local sterilizing immunity to prevent virus replication in the nasopharynx and the lungs as well as virus shedding and transmission. Adenovirus vectors are a promising platform to develop RSV vaccines, but further evaluation of mucosal adenovirus-based prefusion F (preF) vaccines is still needed. In this study, we constructed a recombinant chimpanzee adenovirus serotype 68 vector expressing a second-generation disulfide-stabilized (DS2)trimeric preF protein (ChAd68-PreF). In mice, intranasal immunization with ChAd68-PreF induced dose-dependent increase in RSV-specific secretory IgA (sIgA) in the lower respiratory tract, demonstrating its capacity to elict mucosal immunity. Subsequently, in cotton rats, intratracheal instillation of ChAd68-PreF induced high cross-neutralizing antibody titers against RSV A and RSV B. After RSV A2 challenge, ChAd68-PreF vaccinated animals showed no detectable viral replication in the nose nor in the lungs. Moreover, ChAd68-PreF vaccination did not lead to enhanced respiratory disease (ERD) in cotton rats. These results demonstrate that mucosal delivery of ChAd68-PreF confers potent protective immunity against RSV with good safety profile, warranting further clinical development as a mucosa-targeting RSV vaccine for vulnerable populations.

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) infection in acute respiratory infection (ARI) cases in Guangdong Province from 2023 to 2024. Methods: From August 2023 to July 2024, 16 414 ARI cases in Guangdong Province were selected as the research subjects. The demographic characteristics of the subjects were collected, and multiplex respiratory pathogen detection kits were used to conduct multi-pathogen nucleic acid testing. The HRSV infection status of cases with different characteristics was analyzed and compared. Results: The M (Q1, Q3) of age of ARI cases was 16 (5, 38) years old, including 8 906 males, accounting for 54.3%. The total positive rate of HRSV in ARI cases was 2.46% (404/16 414), with positive rates of 2.64% (235/8 906) in males and 2.25% (169/7 508) in females, showing no statistically significant difference (P=0.110). The highest positive rate of HRSV was found in cases under two years old [7.88% (103/1 307)], and the positive rate decreased with age (P<0.001). The positive rates of HRSV in ILI and SARI cases were 2.37% (261/11 011) and 2.65% (143/5 403), respectively. The positive rate of HRSV in SARI cases under two years old was 11.40% (53/465), which was higher than that in ILI cases [5.94% (50/842)] (P<0.001). The peak detection periods of HRSV were in August 2023 and April 2024. The A subtype was predominant in 2023, but the B subtype became dominant in 2024. Conclusion: Infants and young children under two years old are the high-risk group for HRSV infection, with the peak periods in spring and summer. From 2023 to 2024, the dominant subtype of HRSV shifts from the A subtype to the B subtype.

Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical Hainan Island, China. We retrospectively analyzed 32,329 children (≤18 years) hospitalized at Hainan Women and Children’s Medical Center from January 2021 to December 2024. RSV positivity was determined using targeted next-generation sequencing. In total, 4483/32,329 (13.86%) patients were RSV-positive, with a high positivity in 2021 (20.27%, 957/4721), marked suppression in 2022 (2.03%, 106/5227) during intensive NPIs, and a rebound in 2023–2024 (15.31%, 1490/9732; 15.26%, 1930/12,649). RSV positivity was higher in boys than girls (14.42% vs. 13.00%). Seasonality shifted from a summer–autumn peak in 2021 to a spring–summer predominance in 2023–2024. Among 56 sequenced RSV-positive specimens (29 RSV-A; 27 RSV-B), all RSV-A strains belonged to genotype ON1 (lineages A.D.3 and A.D.5.2), and all RSV-B strains belonged to genotype BA9 (lineages B.D.4.1.1, B.D.E.1, and B.D.E.2). Subtype dominance transitioned from RSV-A (2021–2023; mainly A.D.3) to RSV-B in 2024 (all B.D.E.1). Lineage-specific amino-acid and predicted N-glycosylation changes were observed, including loss of the N179 site in A.D.5.2 and acquisition of N258 in B.D.E.1. These findings indicate that RSV circulation on tropical Hainan was strongly suppressed during intensive NPIs and re-established after policy relaxation, accompanied by earlier seasonal activity and clear lineage replacement, underscoring the need for sustained genomic surveillance to inform locally tailored clinical preparedness and immunization strategies.

Understanding parental decisions to decline or delay infant RSV immunisation, nirsevimab, in Western Australia in 2024.

Respiratory syncytial virus (RSV) causes substantial winter pressure on adult services. In the UK, RSV vaccination currently targets adults aged ≥75 years and care home residents; it remains uncertain whether this age criterion alone meaningfully discriminates risk of poor outcome among adults hospitalised with RSV. We pooled three UK hospital cohorts (one prospective, two retrospective) of adults admitted with acute respiratory infection (ARI) and PCR-confirmed RSV. The primary outcome was intensive care unit/high dependency unit (ICU/HDU) admission or all-cause mortality within 60 days. Prespecified predictors (age, sex and comorbidities) entered a least absolute shrinkage and selection operator (LASSO) penalised logistic regression; selected variables were refitted using standard logistic regression. Discrimination, calibration and decision-analytic performance were assessed using 1000-bootstrap internal validation and decision-curve analysis. Among 334 adults, 37 (11.1%) experienced the primary outcome. An age-only rule mirroring current UK vaccine age-eligibility (≥75 years) demonstrated only modest discrimination (optimism-adjusted area under the receiver operating characteristic curve (AUC) 0.58, 95% CI 0.48 to 0.65) and a compressed distribution of predicted risks. A four-predictor model-including age, COPD, active/previous cancer and dementia-achieved higher discrimination AUC (0.77 (0.69 to 0.85)), a wider spread of predicted risks and the greatest net benefit across clinically plausible escalation thresholds (5-20%). In adults hospitalised with RSV-associated ARI, simple age-based heuristics-including the UK ≥75-year threshold-showed only modest ability to discriminate risk of ICU/HDU admission/60-day mortality once hospitalised. Comorbidity-inclusive approaches may provide more informative hospital-level risk stratification and warrant evaluation in future RSV vaccine-effectiveness and outcome studies. Any application requires external validation, more systematic RSV testing and comparison with physiology-based scores in larger, vaccinated cohorts.

Heterozygous variants in DOCK2 leading to susceptibility to viral illnesses.

Establishing a rapid, broad-spectrum antiviral state in human cells offers a promising strategy to combat viral infections, especially when vaccines or pathogen-specific treatments are unavailable. Here, we evaluate immunostimulatory nucleic acid nanoparticles (iNANPs), identified as potent innate immune activators, for their ability to induce protective antiviral states. By mimicking pathogen-associated molecular patterns, iNANPs engage intracellular pattern recognition receptors to stimulate type I and III interferon responses. We tested iNANPs for antiviral efficacy against a replication-incompetent lentiviral vector pseudotyped with vesicular stomatitis virus (VSV) G protein, as well as replication-competent viruses, including VSV, Sendai virus (SeV), and respiratory syncytial virus (RSV). These viruses vary in their mechanisms of innate immune activation and evasion, providing a robust system to assess iNANP activity. Our results demonstrate that iNANPs dramatically restrict viral infection via induction of a robust IFN response, establishing an antiviral state that impairs replication of all tested viruses. This study highlights the potential of iNANPs as a broad-spectrum antiviral prophylactic platform.IMPORTANCEEstablishing a rapid, broad-spectrum antiviral state in human cells offers a promising strategy to combat viral infections, especially when vaccines or pathogen-specific treatments are unavailable. Here, we evaluate immunostimulatory nucleic acid nanoparticles (iNANPs) identified as potent innate immune activators for their ability to induce protective antiviral states. The highly modular design and tunable physicochemical properties of iNANPs with defined architectures and compositions can be tailored to engage specific innate immune sensors. This same modularity allows a seamless "plug-and-play" integration of diverse therapeutic nucleic acids, as well as other therapeutics and small molecules, directly into the iNANP structure. We tested iNANPs for antiviral efficacy against a replication-incompetent lentiviral vector pseudotyped with vesicular stomatitis virus (VSV) G protein, as well as replication-competent viruses, including VSV, Sendai virus (SeV), and respiratory syncytial virus (RSV). Our results demonstrate that iNANPs significantly restrict viral infection, highlighting their potential as a broad-spectrum antiviral prophylactic platform.

Long-Term Illness in Adults Hospitalized for Respiratory Syncytial Virus Disease, United States, February 2022-September 2023.

Respiratory syncytial virus (RSV) may trigger cardiorespiratory events in adults. To assess the risk of cardiorespiratory events in the 180 days following RSV-related hospitalization compared with a control period in adults. This self-controlled case series study had an observation period from January 1, 2017, through March 31, 2024. Data were obtained from the deidentified Optum Market Clarity Dataset, including RSV-related hospitalization and associated outcomes, which were identified based on diagnosis codes. Adults with 1 or more RSV-related hospitalizations and 1 or more cardiorespiratory events (myocardial infarction [MI], stroke, chronic obstructive pulmonary disease [COPD] exacerbation, congestive heart failure [CHF] exacerbation, and arrhythmia) were included. RSV-related hospitalization. A conditional Poisson regression model was fitted to compare the incidence of cardiorespiratory events during the risk period (ie, ≤180 days after RSV-related hospital index date) and control periods (ie, >21 days before or >180 days after the index date). Incidence rate ratios (IRRs) and 95% CIs were estimated and adjusted for time-varying covariates. A total of 11 887 patients (mean [SD] age, 69.4 [15.5] years; 7303 females [61.4%]) with RSV-related hospitalization were included. An increased risk was associated with each cardiorespiratory event during the first 14 days following RSV-related hospitalization, with the highest IRR estimates observed in the initial 7 days. For MI, the IRRs were 8.7 (95% CI, 6.7-11.2) during days 1 to 7, decreasing to 5.2 (95% CI, 3.7-7.2) during days 8 to 14 and 2.6 (95% CI, 1.6-4.3) during days 15 to 21. For stroke, the IRRs were 7.4 (95% CI, 5.5-10.1), 5.9 (95% CI, 4.2-8.3), and 3.7 (95% CI, 2.3-5.9) during the first 3 weeks with a similar pattern for CHF exacerbation (12.5 [95% CI, 10.5-14.8], 4.1 [95% CI, 3.1-5.5], and 2.4 [95% CI, 1.6-3.6], respectively). For COPD exacerbation and arrhythmia, the IRRs decreased during the first 3 weeks from 23.1 (95% CI, 20.2-26.5) through day 7 to 1.3 (95% CI, 0.8-2.4) during days 15 to 21 and from 16.5 (95% CI, 14.5-18.7) to 1.6 (95% CI, 1.1-2.5), respectively. This study demonstrated that RSV, similar to influenza and SARS-CoV-2, was associated with an increased risk of cardiorespiratory events 2 weeks following RSV-related hospitalization, and some conditions had significant risk elevations up to 180 days after admission. The findings reinforce the need to increase RSV immunization in adults.

Acute otitis media (AOM) affects over 709 million individuals globally each year, more than half of whom are children < 5 years. Respiratory syncytial virus (RSV) is a leading viral cause of pediatric respiratory illness. We aimed to estimate the burden of RSV in children < 5 years with AOM METHODS: We performed a systematic review of studies reporting RSV identified through laboratory testing in children < 5 years with AOM. We searched eight databases from January 1, 1996, to May 9, 2025. We extracted data on RSV proportion in AOM and on co-detection of bacterial pathogens. We reported pooled proportions using random-effects meta-analysis. We included 27 studies encompassing 8342 children with AOM. The pooled proportion of RSV in children with AOM was 16.9% (95% CI 11.0-23.8, I2 = 94.9%). RSV proportion was higher in inpatient-based studies, in studies conducted during peak RSV seasons, and in children aged < 12 months. Among RSV-positive AOM cases, an estimated 67.4% (95% CI 15.4-100) had at least one bacterial co-detection. The most frequent bacteria co-detected were Streptococcus pneumoniae, followed by Haemophilus influenzae and Moraxella catarrhalis. RSV is a common contributor to AOM in children < 5 years. Our findings indicate that RSV-associated AOM often involves concurrent bacterial detection. These results highlight the potential impact of recently introduced passive RSV immunization, such as maternal immunization and long-acting monoclonal antibody, in reducing AOM incidence and its complications. Preventing RSV in early childhood could lower the overall burden of AOM and decrease the need for antibiotics.

RSV-associated hospitalizations in Bangladeshi children under five: Unveiling the disease burden.

Bacterial colonization and life-threatening respiratory syncytial virus infection in children.

Low-concentration sucrose improves respiratory syncytial virus viability under thermal and Freeze-Thaw stress: An efficient solution for virology and vaccine studies.

Respiratory syncytial virus infection in non-severely immunocompromised adults: Clinical features and outcomes from a tertiary university hospital in Argentina.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections in children and the elderly worldwide. RSV pathogenesis is largely driven by exaggerated host immune responses that result in lung injury. In this study, we examined the role of A20 (TNFAIP3), a key regulator of immune signaling, in RSV infection using a BALB/c mouse model. Recombinant lentiviruses encoding TNFAIP3 (A20) or A20-specific shRNA were generated and administered to BALB/c mice. Animals received intravenous lentivectors, challenged intranasally with RSV-A2, and sacrificed on Day 5 postinfection. A20 expression, cytokine and chemokine levels, lung pathology, and viral load were assessed using real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and histopathological analysis. RSV infection significantly induced A20 expression in bronchoalveolar (BAL) cells. Lentivector-mediated modulation of A20 expression produced distinct outcomes: A20 downregulation amplified inflammatory responses, increased immune cell infiltration, and elevated pro-inflammatory mediator secretion in BAL fluid, leading to aggravated lung pathology. In contrast, A20 upregulation did not markedly alter immune cell recruitment, cytokine production, or histopathological changes following RSV infection. A20 downregulation exacerbates inflammation and lung injury following RSV infection, highlighting its critical role in immune regulation during the virus infection. Further studies employing targeted molecular delivery systems and human airway organoid models are warranted to evaluate the therapeutic potential of modulating A20 in RSV disease.

Protecting the Vulnerable: Narrative Review on RSV Vaccines in Adults and Pregnancy.

Limitations of Comprehensive Respiratory Viral Testing in Managing Young Infants with Fever.

Economic impact of RSV prefusion F protein-based (RSVpreF) vaccination and nirsevimab prophylaxis on RSV-associated disease among Japanese infants.

Visceral Leishmaniasis is a systemic vector-borne infection with a poor prognosis if not treated. Classical antiparasitic therapy with liposomal amphotericin B (LAmB) is effective, but occasionally not well-tolerated. An 11-month-old male infant was admitted to our hospital due to prolonged fever, following an RSV infection. The patient had pale skin and splenomegaly, but was hemodynamically stable. An infectious cause was investigated through serology for Leishmania species , Brucella melitensis , Toxoplasma gondii , EBV, CMV, PB19 and Salmonella species . After admission, the infant developed Hemophagocytic lymphohistiocytosis (HLH, with pancytopenia, triglycerides: 346 U/L, ferritin: 1071 ng/mL; γ-globulin was administered without clinical response). On the second hospitalization day, the Leishmania rapid test was positive, while blood polymerase chain reaction identified Leishmania Infantum as the cause of infection, and LAmB was initiated. After the 4th dose, the patient developed hypokalemia, bradycardia and premature supraventricular complexes. The arrhythmia persisted despite electrolyte replacement; amphotericin-induced cardiotoxicity was suspected, and LAmB was discontinued. Oral miltefosine was started after approval by the National Public Health Organization, since the medicine was given in Greece for the first time to a pediatric patient. Miltefosine therapy lasted 1 month, with remission. Hepatotoxicity occurred at the end of the treatment and gradually resolved over the following 4 months with complete normalization of hepatic markers. The child remained asymptomatic at the 1-year follow-up. Leishmaniasis should always be investigated in pediatric patients with secondary HLH, especially in endemic countries. Cardiotoxicity of LAmB is extremely rare; in this case, however, miltefosine is an effective and safe alternative.

ABSTRACTBackgroundMale sex is a well‐known risk factor for respiratory syncytial virus (RSV) hospitalization in children, but there are no data on potential differences in clinical features between boys and girls hospitalized with RSV infection.MethodsWe compared the average population‐based rates of hospitalization and the clinical features of the illness between boys and girls hospitalized with virologically confirmed RSV infection during 2006–2020 at Turku University Hospital, Finland. During this period, testing for RSV was routine in all children admitted with respiratory infections. The comparisons were performed in different age groups of children up to 5 years of age.ResultsAmong all 1204 children < 5 years of age hospitalized with RSV, the average annual RSV hospitalization rates were 4.0/1000 in boys and 3.3/1000 in girls (incidence rate ratio [IRR] 1.21; 95% CI, 1.07–1.35; p = 0.001). The difference was greatest in children aged 3–23 months, among whom the corresponding rates were 5.4/1000 in boys and 3.6/1000 in girls (IRR, 1.50; 95% CI, 1.25–1.80; p < 0.001). The occurrence of respiratory distress was consistently higher in boys than in girls among children aged 6–17 months. In this group of 233 children, 128 of 141 (90.8%) boys had documented respiratory distress, compared with 70 of 92 (76.1%) girls (p = 0.002).ConclusionsExcept for the first 3 months after birth, boys have a 50% higher risk of RSV hospitalization than girls during the first 2 years of life. In that same age group, boys hospitalized with RSV have also significantly more respiratory distress than girls.