Search Results (703)

The biological progression of aging encompasses complex physiological processes. As individuals grow older, their physiological functions gradually decline, including compromised immune responses, leading to immunosenescence. Immunosenescence significantly elevates disease susceptibility and severity in older populations while concurrently compromising vaccine-induced immune responses. This comprehensive review aims to elucidate the implications of immunosenescence for vaccine-induced immunity and facilitate the development of optimized vaccination strategies for geriatric populations, with specific focus on COVID-19, influenza, pneumococcal, herpes zoster, and respiratory syncytial virus (RSV) vaccines. This review further elucidates the relationship between immunosenescence and vaccine-induced immunity. This review presents a systematic evaluation of intervention strategies designed to enhance vaccine responses in older populations, encompassing adjuvant utilization, antigen doses, vaccination frequency modification, inflammatory response modulation, and lifestyle interventions, including physical activity and nutritional modifications. These strategies are explored for their potential to improve current vaccine efficacy and inform the development of next-generation vaccines for geriatric populations. Full article

The beneficial effect of milk kefir on respiratory heath has been previously demonstrated; however, water kefir and kefiran in the context of respiratory viral infections have not been investigated. Water kefir and kefiran could be alternatives to milk kefir for their application in persons with lactose intolerance or milk allergy and could be incorporated into vegan diets. Using mice models, this work demonstrated that the oral administration of water kefir or kefiran can modulate the respiratory Toll-like receptor (TLR3)-mediated innate antiviral immunity and improve the resistance to respiratory syncytial virus (RSV) infection. The treatment of mice with water kefir or kefiran for 6 days improved the production of interferons (IFN-β and IFN-γ) and antiviral factors (Mx2, OAS1, RNAseL, and IFITM3) in the respiratory tract after the activation of the TLR3 signaling pathway, differentially modulated the balance of pro- and anti-inflammatory cytokines, reduced RSV replication, and diminished lung tissue damage. Maintaining a proper balance between anti-inflammatory and pro-inflammatory mediators is vital for ensuring an effective and safe antiviral immune response, and the results of this work show that water kefir and kefiran would help to maintain that balance promoting a controlled inflammatory response that defends against infection while minimizing tissue damage. Full article

The study highlights the significant changes in respiratory virus epidemiology following the lifting of COVID-19 restrictions. Method: In this single-centre retrospective study, the virological readouts of adenovirus (AdV), influenza virus A (IAV), influenza virus B (IBV), parainfluenza viruses (PIV) 1, 2, 3, 4, respiratory syncytial virus (RSV), and coupled enterovirus and rhinovirus (EV/RV) were extracted from the respiratory specimens of paediatric patients in Hong Kong from January 2015 to February 2024. The subjects were stratified into five age groups. Results: The study included 18,737 and 6001 respiratory specimens in the pre-COVID-19 and post-COVID-19 mask mandate period, respectively. The mean age of hospitalised patients increased from 3.49 y ± 0.03 y to 4.37 y ± 0.05 y after the COVID-19 lockdown. The rates of single-virus infection and co-infection were significantly higher in the post-COVID-19 mask mandate period. The odds ratio for AdV for all age groups (OR: 4.53, 4.03, 2.32, 2.46, 1.31) and RSV in older children from 3 years old and above (OR: 1.95, 3.38, p < 0.01) were significantly elevated after the COVID-19 outbreak. Conclusions: Our findings suggest that public health measures to contain COVID-19 may have unintended consequences on children’s natural exposure and immunity to other respiratory viruses, potentially increasing their morbidity in the post-pandemic era. Full article

Bovine respiratory syncytial virus (BRSV) is an enveloped RNA virus that utilizes clathrin-mediated endocytosis for cell entry and is a significant pathogen in bovine respiratory disease (BRD). Heat shock protein family A member 4 (HSPA4), a member of the HSP70 family, is known to be involved in the progression of various cancers. However, its role in virus entry has not been previously explored. Through experiments involving Western blot analysis, virus titer, and virus copies analysis, we demonstrated that HSPA4 can regulate BRSV entry and replication. The specific regulation mode is to enhance BRSV entry by promoting clathrin-mediated endocytosis. We used Western blot, virus titer, virus copies analysis, and IFA to demonstrate that HSPA4 can promote clathrin heavy chain protein (CHC) expression and further promote BRSV entry by activating the PI3K–Akt signaling pathway. Furthermore, we observed that HSPA4 boosts the efficiency of clathrin-mediated endocytosis by increasing the ATPase activity of heat shock cognate protein 70 (HSC70), thereby facilitating BRSV entry. Additionally, our investigation into the impact of HSPA4 on the entry of other viruses revealed that HSPA4 can facilitate the entry of a variety of viruses into host cells. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn²⁺) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2′, suggesting interference with SARS-CoV-2’s spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies. Full article

Which patients should be monitored for coinfections or should receive empirical antibiotic treatment, in patients with an acute viral respiratory infection, is largely unknown. We evaluated the prevalence, characteristics, outcomes of coinfected patients, and risk factors associated with a coinfection among patients with an acute viral infection. A retrospective, single-center study recruited consecutive patients from October 2022 to March 2023 presenting to the emergency department with signs of a respiratory tract infection. Patients were screened for respiratory viruses and bacterial/fungal secondary infections according to local standard procedures. Outcomes included severe disease, in-hospital complications, all-cause in-hospital and ICU-related mortality, time to death, time to discharge, and time to coinfection. The analysis included 652 patients. A viral infection and a secondary bacterial/fungal infection were detected in 39.1% and 40% of cases. Compared with the rest of the cohort, coinfected patients had more frequently severe disease (88.3%, p < 0.001; 51% in patients with SARS-CoV-2) and higher in-hospital mortality (16.5%, p = 0.010). Nephropathy (OR 3.649, p = 0.007), absence of COVID-19 vaccination (OR 0.160, p < 0.001), SARS-CoV-2 infection (OR 2.390, p = 0.017), and lower blood pressure at admission (OR 0.980, p = 0.007) were independent risk factors for coinfection. Multidrug-resistant pathogens were detected in 30.8% of all coinfections. Patients with a viral infection are at high risk of bacterial coinfections, which carry a significant morbidity and mortality burden. Full article

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections. Full article

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization. Full article

The impact of common respiratory virus infections on adults and older individuals in the community is unclear, excluding seasonal influenza viruses. We examined FilmArray® tests performed on 1828 children aged <10 years and 10,803 adults, including cases with few respiratory symptoms, between January 2021 and June 2024. Approximately 80% of the children tested positive for ≥1 viruses, while 9.5% of the adults tested positive mostly for severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). Besides SARS-CoV-2 infection, 66 out of 97 patients (68.0%) aged >60 years with rhinovirus/enterovirus (RV/EV), respiratory syncytial virus (RSV), parainfluenza virus-3 (PIV-3), or human metapneumovirus (hMPV) infection required hospitalization, of whom seven died; 26 out of 160 patients (16.3%) aged <60 years required hospitalization mostly because of deterioration of bronchial asthma, with no reported deaths. In older patients with RV/EV infection, three with few respiratory symptoms died due to worsened heart failure. Although the frequency of common respiratory virus infections in older adults is low, it may be overlooked because of subclinical respiratory symptoms, and its clinical significance in worsening comorbidities in older adults should not be underestimated. Full article

Bovine respiratory syncytial virus (BRSV) is a major respiratory pathogen in cattle and is relevant to the livestock industry worldwide. BRSV is most severe in young calves and is often associated with stressful management events. The disease is responsible for economic losses due to lower productivity, morbidity, mortality, and prevention and treatment costs. As members of the same genus, bovine and human RSV share a high degree of homology and are similar in terms of their genomes, transmission, clinical signs, and epidemiology. This overlap presents an opportunity for One Health approaches and translational studies, with dual benefits; however, there is still a relative lack of studies focused on BRSV, and the continued search for improved prophylaxis highlights the need for a deeper understanding of its immunological features. BRSV employs different host-immunity-escaping mechanisms that interfere with effective long-term memory responses to current vaccines and natural infections. This review presents an updated description of BRSV’s immunity processes, such as the PRRs and signaling pathways involved in BRSV infection, aspects of its pathogeny, and the evading mechanisms developed by the virus to thwart the immune response. Full article

(1) Background: To describe hospitalizations due to respiratory syncytial virus (RSV) infection among children and elderly patients with asthma. (2) Methods: We used a nationwide discharge database to select patients with asthma aged 0 to 15 years and ≥65 years admitted to Spanish hospitals from 2016 to 2022. (3) Results: We identified 49,086 children and 471,947 elderly patients hospitalized with asthma (3.52% and 0.51%, respectively, with RSV). The proportion of RSV increased over time in children with asthma (from 1.44% to 7.4%, p < 0.001) and in elderly individuals (from 0.17% to 1.01%, p < 0.001). Among children with RSV infection, the presence of influenza (OR 3.65; 95% CI 1.46–9.1) and pneumonia (OR 1.85; 95% CI 1.02–3.55) increased the risk of poor outcome. The presence of RSV was associated with severity in these patients, defined by use of mechanical ventilation and/or admission to the intensive care unit (OR 1.44; 95% CI 1.11–1.86). In elderly patients with RSV infection, older age, congestive heart failure, COVID-19, and pneumonia increased the risk of in-hospital mortality (IHM). However, RSV infection was not associated with IHM (OR 0.88; 95% CI 0.68–1.15) in these patients. (4) Conclusion: Our results highlight the impact of RSV infection in children and elderly patients hospitalized with asthma. Strategies to improve surveillance, prophylaxis, and management of RSV infection should be evaluated. Full article

Background/Objectives: Respiratory illnesses frequently lead to hospitalization in adults aged 60 and older, especially due to respiratory viral infectious (RVI). This study investigates hospitalization patterns and characteristics of RVI at HM Hospitals from October 2023 to March 2024; Methods: We retrospectively explored hospitalizations of patients aged 60 years and older with RVIs, gathering data on demographics, clinical profiles, comorbidities, and treatments. Outcomes included hospitalization, ICU admissions, and mortality, and independent factors associated with outcomes were identified using a multi-state model; Results: From October 2023 to March 2024, from a total of 3258 hospitalizations, 1933 (59.3%) were identified as positive for RVIs. Overall, SARS-CoV-2 was the most prevalent (52.6%), followed by influenza (32.7%), and RSV (11.8%). Most RVI involved single infections (88.2%). Hospitalization rates increased with age for SARS-CoV-2 (333.4 [95% CI: 295.0–375.2] to 651.6 [95% CI: 532.1–788.4]), influenza (169.8 [95% CI: 142.6–200.7] to 518.6 [95% CI: 412.1–643.1]), and RSV (69.2 [95% CI: 52.2–90.0] to 246.0 [95% CI: 173.8–337.5]), with SARS-CoV-2 showing the highest rate, followed by influenza and RSV. In the multi-state model, RSV infection significantly increased ICU admission risk (HR: 2.1, 95%, p = 0.037). Age on admission (HR: 1.1, 95%, p < 0.001) and Charlson score (HR: 1.4, 95%, p = 0.001) were associated with transitioning from admission to death. ICU to death risks included age at admission (HR: 1.7, 95%, p < 0.001); Conclusions: RVI in adults 60 years and older are associated with high hospitalization and mortality rates, primarily driven by influenza and SARS-CoV-2, followed by RSV. Age and comorbidities significantly impact disease severity, emphasizing the need for targeted prevention and management strategies for RSV in this vulnerable population. Full article

Acute respiratory infection is one of the leading causes of morbidity and mortality among children in low- and middle-income countries. Due to limited diagnostic capability, many respiratory pathogens causing influenza-like illness go undetected. This study aims to detect enterovirus, respiratory syncytial virus, seasonal coronavirus and respiratory pathogens other than influenza in patients with influenza-like illness. A total of 997 (54.3%) respiratory samples (collected in the years 2016–2018) were randomly selected from 1835 influenza-negative samples. The xTAG Respiratory Viral Panel (RVP) FAST v2 panel was used to detect respiratory pathogens including enterovirus/rhinovirus (EV/RV), respiratory syncytial virus (RSV) and seasonal coronavirus (HKU1, OC43, NL63 and 229E). A total of 78.7% (785/997) were positive for respiratory viruses. Of these viruses, EV/RV was detected in 36.3% (362/997), which is the highest number, followed by RSV in 13.7% (137/997). The seasonal coronaviruses HKU1 and OC43 (1.5%, 15/997), NL63 (1.2%, 12/997) and 229E (1%, 10/997) were also detected. The EV/RV-positive samples were sequenced, of which 16.7% (5/30) were confirmed as EVs and were identified as coxsackievirus (CV) types CVB5, CVB3, CV21 and CVB2. The findings of this study highlight the importance of strengthening influenza-like illness surveillance programs in the region by including other respiratory viruses in their scope besides seasonal human influenza viruses. Full article

Background: During seasonal influenza activity, circulation of other respiratory viruses (ORVs) may contribute to the increased disease burden that is attributed to influenza without laboratory confirmation. The objective of this study was to characterize and evaluate the magnitude of this contribution over 12 seasons of influenza using the Acute Respiratory Infection Sentinel Surveillance system in Catalonia (PIDIRAC). Methods: A retrospective descriptive study of isolations from respiratory samples obtained by the sentinel surveillance network of physicians was carried out from 2008 to 2020 in Catalonia, Spain. Information was collected on demographic variables (age, sex), influenza vaccination status, epidemic activity weeks each season, and influenza laboratory confirmation. Results: A total of 12,690 samples were collected, with 46% (5831) collected during peak influenza seasonal epidemic activity. In total, 49.6% of the sampled participants were male and 51.1% were aged <15 years. Of these, 73.7% (4298) of samples were positive for at least one respiratory virus; 79.7% (3425 samples) were positive for the influenza virus (IV), with 3067 samples positive for one IV type, 8 samples showing coinfection with two types of IV, and 350 showing coinfection of IV with more than one virus. The distribution of influenza viruses was 64.2% IVA, 35.2% IVB, and 0.1% IVC. Of the other respiratory viruses identified, there was a high proportion of human rhinovirus (32.3%), followed by human adenovirus (24.3%) and respiratory syncytial virus (18; 7%). Four percent were coinfected with two or more viruses other than influenza. The distribution of coinfections with ORVs and influenza by age groups presents a significant difference in proportions for 0–4, 5–14, 15–64 and >64 (21.5%, 10.8%, 8.2% and 7.6%: p < 0.001). A lower ORVs coinfection ratio was observed in the influenza-vaccinated population (11.9% vs. 17.4% OR: 0.64 IC 95% 0.36–1.14). Conclusions: During the weeks of seasonal influenza epidemic activity, other respiratory viruses contribute substantially, either individually or through the coinfection of two or more viruses, to the morbidity attributed to influenza viruses as influenza-like illness (ILI). The contribution of these viruses is especially significant in the pediatric and elderly population. Identifying the epidemiology of most clinically relevant respiratory viruses will aid the development of models of infection and allow for the development of targeted treatments, particularly for populations most vulnerable to respiratory viruses-induced diseases. Full article

The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a lack of ideal animal models. Despite the demonstration of efficacy in animal studies, numerous RSV vaccine candidates have been unsuccessful in clinical trials, primarily due to the lack of suitable animal models. The most commonly utilized animal models for RSV research are cotton rats, mice, lambs, and non-human primates. These animals have been extensively employed in mechanistic studies and in the development and evaluation of vaccines and therapeutics. However, each model only exemplifies some, but not all, aspects of human RSV disease. The aim of this study was to provide a comprehensive summary of the disease symptoms, viral replication, pathological damage, and enhanced RSV disease (ERD) conditions across different RSV animal models. Furthermore, the advantages and disadvantages of each model are discussed, with the intention of providing a valuable reference for related RSV research. Full article