Search Results (354)

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants worldwide. Despite extensive study in animal models and humans, fundamental age-dependent differences in mucosal immunity continue to limit the development of durable protective strategies in early life. Compared to adults, infants mount weaker humoral responses to RSV, underscoring the urgent need for effective vaccines in this age group. Immunoglobulin A (IgA), the dominant antibody isotype at respiratory mucosal surfaces, plays a central role in limiting viral replication and disease severity during RSV infection. While IgA limits RSV severity in adults, infants fail to generate robust IgA responses. Impaired IgA responses in infancy reflect unique immune regulatory pathways that shape early-life antiviral immunity. Emerging evidence highlights a critical role for regulatory B cells (Bregs), particularly neonatal Bregs (nBregs), in suppressing antiviral responses, limiting class switch recombination, and contributing to severe RSV disease. This review summarizes current evidence on IgA regulation during RSV infection, with particular emphasis on age-specific B-cell responses and the emerging role of Bregs. Improved understanding of these mechanisms has direct implications for the rational design of vaccines and immunomodulatory strategies tailored to infants. Full article

Background: Viral respiratory tract infections (RTIs) frequently lead to emergency department (ED) presentations and hospital admissions, particularly among older adults and individuals with underlying health conditions. Identifying patients at increased risk for hospitalization is essential for optimizing triage and resource allocation. This study aimed to determine independent demographic, clinical, and virological predictors of hospital admission among adults presenting with confirmed viral RTIs. Methods: A retrospective cohort study was conducted at a tertiary hospital between September 2022 and May 2024. Adult patients with molecularly confirmed viral RTIs were included. Demographic, clinical, and microbiological data were extracted from electronic medical records. Predictors of admission were assessed using univariate and multivariate logistic regression. Results: Among 311 patients, 147 (47.3%) required hospitalization. Hospitalized patients were significantly older and more likely to present with fever, cough, tachypnea, dyspnea, chest pain, comorbidities, and lower or mixed respiratory tract infections (all p < 0.001). In multivariate analysis, older age, fever, cough, and lower or mixed RTIs were strong independent predictors of admission. Several viral pathogens, including human rhinovirus, non–SARS-CoV-2 coronaviruses, influenza A, and parainfluenza virus, were associated with reduced odds of hospitalization. Conclusions: Age, comorbidity burden, and lower respiratory tract involvement are key determinants of hospitalization in viral RTIs. Integrating clinical and virological data may improve risk stratification and guide ED triage during seasonal and emerging respiratory virus activity. Full article

Interferons (IFNs) are essential mediators of the innate immune response to viral infections. Among the type III IFNs, the role of IFN-λ4 in respiratory viral infections remains largely understudied. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are clinically significant pneumoviruses that elicit divergent IFN responses in epithelial cells. Here, we investigate the virus-specific induction and antiviral activity of IFN-λ4 by HMPV and RSV infections. We demonstrate that RSV induces a limited expression of IFN-λ4, which is regulated by the expression of the NS1 protein. Furthermore, RSV and HMPV rely primarily on RIG-I for IFN-λ4 induction. Finally, we show that IFN-λ4 exerts antiviral activity against both viruses, with RSV displaying greater sensitivity. These findings highlight the antiviral role of IFN-λ4 to clinically relevant respiratory viruses. Full article

Respiratory viruses such as SARS-CoV-2, influenzas A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human parainfluenza virus type 3 (HPIV-3), and rhinoviruses remain major causes of global morbidity. Their rapid evolution, high transmissibility, and limited therapeutic options, together with the absence of approved vaccines for several pathogens, highlight the need for broad-acting and pathogen-independent antiviral strategies. Nitric oxide exhibits antiviral activity through redox-dependent mechanisms, including S-nitrosylation of cysteine-containing viral proteins and disruption of redox-sensitive structural domains. Clinical studies conducted during the SARS-CoV-2 pandemic demonstrated that a nitric oxide nasal spray (NONS) rapidly reduced nasal viral load and transmission. In this study, we evaluated the in vitro virucidal activity of the NONS against a panel of clinically relevant respiratory viruses representing four major virus families. Virus suspensions of approximately 10⁴ CCID₅₀ were exposed to a full-strength NONS for contact times ranging from 5 s to 2 min at room temperature, followed by neutralization and quantification of residual infectivity using endpoint dilution assays. The NONS rapidly reduced viral infectivity across all viruses tested, achieving >3 log₁₀ reductions within 2 min. SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, Omicron BA.1, and XBB 2.0 were reduced to levels at or below the assay detection limit within 30 s to 2 min. Influenza A and B viruses showed the fastest loss of infectivity, reaching detection limits within 10–15 s. RSV, hMPV, HPIV-3, and human rhinovirus 14 were similarly inactivated within 1–2 min. These findings demonstrate that the NONS exhibits rapid and broad-spectrum virucidal activity against diverse respiratory viruses and supports its potential role in pandemic preparedness but also seasonal use. Full article

With new emerging diseases such as COVID-19 and an increasing incidence of cancer, there remains a significant need for investigating new therapeutic options to treat a wide range of ailments and disorders. Peppermint (Mentha × piperita) and white snakeroot (Ageratina altissima) have been used medicinally by native people in the Midwestern United States for centuries. However, the antiproliferative and antimicrobial properties of the aqueous extracts of these plants remain unclear. In this study, we evaluate the therapeutic potential of peppermint and white snakeroot aqueous leaf extracts by examining their activity against mammalian cancer cells, bacteria, and viruses. Both peppermint and snakeroot extracts showed no reductions in viability at concentrations lower than 25 mg/mL and 10 mg/mL, respectively, in two different cancer lines, HEp-2 and DBT-9 cells, in vitro. While treatment with the snakeroot extract resulted in significant disruption to cytoskeletal organization in HEp-2 cells at a concentration of 10 mg/mL, peppermint and snakeroot extracts did not have a major impact on the viability or proliferation of the cancer cell lines tested. Peppermint and snakeroot were then evaluated for antibacterial activity against four different bacterial pathogens. Significant inhibition of bacterial replication was observed for E. coli (at concentrations greater than 0.1 mg/mL) and S. aureus (at concentrations greater than 1 mg/mL) treated with either peppermint or snakeroot extracts. No significant activity was observed against the bacterial strains P. aeruginosa and S. pyogenes. Peppermint (EC₅₀ = 2.36 mg/mL) and snakeroot (EC₅₀ = 2.64 mg/mL) significantly reduce infectivity and replication (at concentrations above 0.2 mg/mL) of the major human pathogen, human respiratory syncytial virus (hRSV). However, testing for antiviral activity against a mouse coronavirus (murine hepatitis virus, MHV) showed no impact on replication at concentrations up to 2.5 mg/mL. Lastly, chemical analysis of the extracts identified several prominent compounds, which were subsequently evaluated for their biological contributions to the observed plant extract phenotypes. Two of the identified compounds, 1,8-cineole (Eucalyptol) and menthol, show significant antimicrobial activity. We report that aqueous extracts of peppermint and white snakeroot exhibit specific antibacterial and antiviral activities that support further investigation for therapeutic potential. Full article

Human respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract infections in infants and immunocompromised populations, causing approximately 160,000 annual deaths globally. Despite recent approvals of prefusion F (pre-F) protein-based vaccines (Arexvy, Abrysvo) for older adults and pregnant women, pediatric vaccine development faces unique challenges including enhanced respiratory disease (ERD) risks, maternal antibody interference, and immature infant immune responses. Meanwhile, G protein glycosylation variability and NS1/NS2-mediated interferon suppression remain the outstanding difficulties in structure-based vaccine design. Additionally, current animal models demonstrate notable constraints in virus replication, host susceptibility, immune responses, clinical symptoms, and ERD phenomena. This review synthesizes current obstacles and innovative strategies, highlighting that the selection of multi-antigen strategies, appropriate adjuvants, and the development of more precise preclinical animal models are critical elements that will determine the efficacy and safety of future RSV vaccines. Full article

Background: Rapid pathogen detection is crucial for the timely containment of outbreaks, particularly for respiratory infectious diseases which are highly transmissible and possess high epidemic potential. Methods: We developed a sensitive reverse transcription recombinase-aided amplification (RT-RAA) assay for the rapid detection of six common respiratory viruses: respiratory syncytial virus type A (RSV A), influenza A virus (Flu A), influenza B virus (Flu B), human parainfluenza virus (HPIV), SARS-CoV-2 and adenovirus (ADV). The assay employs a single, standardized protocol for the on-demand detection of any one of the six targets. Its performance was validated using nucleic acid standards and clinical pharyngeal swab specimens. Results: The assay enables rapid detection within 20 min at 39 °C using a portable, self-powered device. It demonstrated high sensitivity, with detection limits below 10³ copies/mL for all targets and as low as 10¹ copies/mL for ADV. Cross-reactivity testing with 21 other pathogens confirmed excellent specificity. Validation with 85 clinical samples showed 100% concordance with RT-PCR, while offering significantly faster results and enhanced portability compared to RT-PCR. Conclusions: This sensitive, specific, and user-friendly RT-RAA assay provides a robust tool for rapid detection of respiratory viruses, particularly suitable for deployment in resource-limited settings and point-of-care testing during outbreaks. Full article

Post-translational modifications (PTMs) are crucial chemical alterations occurring on proteins post-synthesis, impacting various cellular processes. During viral infections, PTMs are shown to play a multitude of roles in viral replication, host interaction, and immune evasion. Thus, these modifications can influence infectivity, with direct impact on the anti-viral host immune responses and potentially viral adaptation across species. This field is still scarcely explored, whilst understanding PTMs is not only important to advance the knowledge of virus pathology but also potentially to provide insights for vaccine development. In this review, we attempt to summarize the latest findings mainly published over the last 10 years, focusing on the roles of PTMs involved in virus infection and anti-viral immune responses, in the context of relevant human respiratory infections: influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. We decided to concentrate on these three viruses because they currently represent a global health problem due to recurrent outbreaks and pandemic potential. A deeper characterization of the PTMs may help in understanding virus–host interaction with possible implications on curative strategies. Further, we will report on cutting-edge technologies to study in vitro virus infection in different cellular-based systems. In particular, we describe and discuss the application of 2D and 3D lung organoid cell-culture systems as in vitro models to mimic respiratory environments and to study the PTMs in a controlled setting. Finally, we will discuss the importance of PTMs in the context of next-generation vaccine design, especially for their potential role to offer effective protection against respiratory viruses. Full article

Background/Objectives: Human Respiratory Syncytial Virus (HRSV) is a major global cause of acute lower respiratory infections in children. With recent approval of pre-fusion F protein-based vaccines and monoclonal antibodies, ongoing molecular surveillance is critical. This study examined HRSV molecular epidemiology and evolution in Riyadh, focusing on mutations in the attachment (G) and fusion (F) glycoproteins and their potential impact on vaccine efficacy. Methods: Nasopharyngeal aspirates (NPAs) (200 samples) were collected from pediatric patients. HRSV-positive samples were typed, and the G gene hypervariable region and F gene were sequenced. Sequence and phylogenetic analyses were performed to identify circulating genotypes and amino acid substitutions. Results: HRSV was detected in 15% of samples, with HRSV-B slightly predominant over HRSV-A. Infants aged 2–5 months had the highest incidence rate of infection. The ON1 subgenotype remained dominant. The duplicated region of the G gene showed constrained evolution, with 18 variable and 6 conserved residues over 13 years. In the F protein, HRSV-A isolates exhibited high conservation, with only three amino acid substitutions in antigenic sites (Ø and II). Sites III, IV, and V remained fully conserved. In contrast, HRSV-B isolates displayed eight substitutions in antigenic sites, including six in site II (palivizumab-binding epitope). Conclusions: Given the highly effective HRSV prophylactics, including the approved vaccines and monoclonal antibodies, these mutations raise critical concerns regarding vaccine efficacy against HRSV-B. These findings underscore the necessity of sustained, seasonal molecular surveillance to monitor the emergence of variants and provide a molecular basis for further clinical studies. Full article

Ultraviolet (UV) disinfection is a powerful method for inactivating viruses. However, comparative wavelength-dependent sensitivities among human viruses and bacteriophages remain poorly characterized. Here, we evaluated the virucidal efficiencies of UV-light emitting diode (UV-LED) against multiple coliphages (MS2, Qβ, PhiX174, and T1) and mammalian viruses, including respiratory syncytial virus (RSV) and human metapneumovirus (HMPV). We used a standardized irradiation system equipped with interchangeable UV-LED modules (250–365 nm), a low-pressure mercury lamp (254 nm), and a filtered krypton-chloride excimer lamp (222 nm). All coliphages exhibited wavelength-dependent inactivation with maximal efficiency at 263–270 nm, closely matching the action spectra of RSV and HMPV (r > 0.94, p < 0.001). However, their absolute UV sensitivities were markedly lower: under 254–281 nm irradiation. RSV and HMPV were approximately 21 and 12 times more sensitive than MS2, respectively. In contrast, far-UVC (222 nm) irradiation reduced these differences, indicating simultaneous damage to viral genomes and structural proteins. These results demonstrated that coliphages and human viruses exhibit similar wavelength-dependent sensitivity to UV-LED irradiation but differ in their absolute susceptibility. Therefore, while coliphages can be conservative surrogates for evaluating UV-LED virucidal performance, their applicability to far-UVC assessments should be interpreted with caution. Full article

Background/Objectives: Given the overlapping seasonality of influenza (Flu) and respiratory syncytial virus (RSV) infections in human populations, Flu–RSV combination vaccines are urgently needed. However, development of combo-vaccines is often faced with intra-vaccine interference which could compromise vaccination outcomes. Here we present an approach to overcoming this problem using a microneedle array patch (MAP)-based combo-vaccine with minimum intra-vaccine interference. Methods: Vaccine-laden dissolving MAPs were fabricated using a two-step micro-molding process with polyvinyl alcohol as major excipient. A partition-loading strategy was adopted to ensure spatially segregated distribution of a split-virus Flu vaccine and recombinant prefusion protein of RSV in separate MAP sectors. Serum samples from BALB/c mice post-vaccination were assessed for titers of binding and neutralizing antibodies against the viruses. Live virus challenge studies were carried out to assess the protection efficacy of the MAP-based vaccines. Results: Although i.m. administered standalone Flu and RSV vaccines were able to induce strong IgG responses in BALB/c mice, bidirectional intra-vaccine interference was observed when the two vaccines were co-administered in premixed form. However, when the two vaccines were loaded onto nonoverlapping sectors of D-MAPs for intradermal vaccination, the intra-vaccine interference effect was effectively overcome. The partition-loaded MAP-Flu/RSV combo-vaccine elicited antigen-specific IgG with robust virus-neutralizing activity and was strongly efficacious against either virus in challenge studies. Conclusions: Our data provide proof-of-concept evidence for the potential usefulness of partition-loaded MAPs in overcoming a critical barrier in vaccinology and offer a promising platform for future clinical translation. Full article

Since the emergence of COVID-19, the epidemiological and seasonal patterns of respiratory pathogens have shifted, highlighting the need for ongoing surveillance. This study investigated the epidemiology, seasonal trends, and age-specific detection of respiratory viruses among patients with acute respiratory infections (ARIs) in Thailand from January to December 2024. Eight respiratory viruses were detected using multiplex real-time RT-PCR. Of 7853 samples, 60.8% (4777) tested positive. The most frequently detected pathogens were influenza virus (IFV, 24.8%), SARS-CoV-2 (21.5%), and human rhinovirus (HRV, 20.8%). IFV showed biannual peaks during the cold and rainy seasons, SARS-CoV-2 peaked in the warm months, and HRV circulated year-round. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) were primarily detected during the rainy season (July–November), reflecting a return toward pre–COVID-19 seasonal patterns. Age-specific differences were notable: HRV was most prevalent in children < 5 years, IFV predominated among those aged 6–18 years, and adults ≥ 19 years were mainly positive for IFV and SARS-CoV-2. Co-infections were most frequent in children aged 3–5 years, often involving HRV. These findings provide updated insights into post–COVID-19 viral epidemiology, emphasize the importance of age- and season-specific surveillance, and support the development of effective public health strategies for ARI control. Full article

The epidemiology of respiratory viruses shifted considerably following the COVID-19 pandemic and the subsequent rollback of non-pharmaceutical interventions (NPIs). The initial global containment strategies implemented during the SARS-CoV-2 outbreak profoundly altered viral transmission dynamics and circulation patterns. As the World Health Organization (WHO) declared COVID-19 no longer a public health emergency in May 2023, viral circulation began reverting to pre-pandemic trends. This retrospective observational study examined the evolving epidemiological patterns of respiratory infections during and after the lifting of NPI, assessing associated clinical manifestations and their relationship with patient-specific risk factors. Data were collected from 307 patients tested between October 2021 and December 2024 using a respiratory multiplex PCR at the Rodolphe Mérieux Laboratory in Lebanon. Results revealed a reemergence of pre-pandemic seasonal trends for most viruses. Rhinovirus remained the most prevalent pathogen, likely due to the absence of a vaccine. Respiratory syncytial virus (RSV) and Influenza A resumed their characteristic winter peaks, while human metapneumovirus (HMPV) showed no co-infections, suggesting viral interference. The persistence of Influenza A and SARS-CoV-2 appeared influenced by vaccine coverage, viral mutations, and environmental factors. Multiplex PCR testing proved to be a valuable yet costly tool for both diagnosis and epidemiological surveillance. Overall, this study highlights the importance of continued viral monitoring in the post-NPI period, reflecting both the effectiveness of NPIs in limiting viral spread and the importance of ensuring wider access to advanced diagnostic methods. Full article

Viral respiratory infections pose a significant risk for pediatric cancer patients and may lead to a delay in chemotherapy, prolonged hospitalization, and mortality. Limited data exist regarding the contributors to adverse clinical outcomes. The present study aims to describe the associations between clinical, epidemiological, and laboratory factors and severe outcomes of respiratory viral infections among children with cancer. This was a retrospective cohort study among pediatric cancer patients treated in the Pediatric Hematology–Oncology Department at Rambam Health Care Campus from 2016 to 2022. Patients with a positive rt-qPCR test for one of the following viruses were included: Adenovirus, Respiratory Syncytial Virus (RSV), Human Metapneumovirus (HMPV), SARS-CoV-2, Parainfluenza, or Influenza. Demographic, clinical, and laboratory data were collected for each case. GEE analyses were conducted to assess the associations between independent variables and severe outcomes (admission to the Pediatric Intensive Care Unit (PICU), hospitalizations exceeding seven days, co-bacterial infections, and mortality within 30 days). A total of 366 viral infections episodes were identified among 238 patients. There were 187 (51%) children with hematological malignancies, 113 (31%) with solid tumors, and 66 patients (18%) who had undergone bone marrow transplantation. Influenza was the most frequently detected virus, accounting for 89 events (24%), followed closely by Adenovirus, with 82 events (23%). Among the 38 severe events, prolonged hospitalization was the most prevalent outcome, occurring in 33 cases. Adenovirus infection was significantly associated with severe outcomes (OR = 2.97, p = 0.010), and antibiotic therapy was associated with 3.62 times higher odds of severe outcomes (p = 0.010). Patients presenting with O2 saturation levels below 92% had 5.71 times higher odds of experiencing severe outcomes. Among the subgroup of hematological malignancies, RSV was positively associated with severe outcomes (OR = 4.08, p = 0.048). Adenovirus was associated with severe outcomes in pediatric cancer patients, highlighting its prevalence and potential for treatment. Similarly, RSV was associated with adverse outcomes specifically among hematological cancer patients, emphasizing the importance of vaccination. A very low mortality from viral infection was also notable. Full article

Background: Respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection (LRTI) in infants, the elderly, and immunocompromised individuals. This review focuses on the progress of RSV vaccine development, especially subunit vaccines targeting the fusion protein (F) and attachment glycoprotein (G), aiming to summarize key strategies, challenges, and future directions in the field. Methods: The review is based on a comprehensive literature search and analysis of recent studies on RSV vaccine development, with a specific focus on subunit vaccines and related technologies. Results: Approved vaccines such as Abrysvo and Arexvy utilize structural engineering to stabilize the prefusion conformation of the F protein (PreF), thereby exposing neutralizing epitopes. Subunit vaccine candidates such as DS-Cav1 and DT-PreF enhance stability through disulfide bonds and dityrosine linkages, while ADV110 targets the conserved domain of the G protein to elicit cross-strain immunity. Virus-like particle (VLP) vaccines like IVX-A12 combine RSV and human metapneumovirus antigens to provide broad-spectrum immunity. However, challenges exist, including maintaining PreF stability, overcoming immunosenescence in the elderly, and addressing safety concerns like Guillain-Barré syndrome (GBS). Conclusions: Future RSV vaccine development should center on combined PreF-G protein vaccines, VLP technology, and optimizing cold-chain logistics to improve global accessibility and overcome existing challenges, thereby providing more effective prevention and control of RSV infections. Full article