Abstract
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%–70% of children have been infected by RSV. In addition, ...early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.
Respiratory syncytial virus (RSV) is a highly contagious seasonal virus and the leading cause of Lower Respiratory Tract Infections (LRTI), including pneumonia and bronchiolitis in children. ...RSV-related LRTI cause approximately 3 million hospitalizations and 120,000 deaths annually among children <5 years of age. The majority of the burden of RSV occurs in previously healthy infants. Only a monoclonal antibody (mAb) has been approved against RSV infections in a restricted group, leaving an urgent unmet need for a large number of children potentially benefiting from preventive measures. Approaches under development include maternal vaccines to protect newborns, extended half-life monoclonal antibodies to provide rapid long-lasting protection, and pediatric vaccines. RSV has been identified as a major global priority but a solution to tackle this unmet need for all children has yet to be implemented. New technologies represent the avenue for effectively addressing the leading-cause of hospitalization in children <1 years old.
Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious ...seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.
Respiratory syncytial virus (RSV) is widely known as a frequent cause of respiratory distress among adults, particularly in older people. Recent years have witnessed several improvements in ...respiratory virus detection, leading to more questions about therapeutic management strategies.
This narrative review focuses on the RSV burden in older people and adults with risk factors and provides an update on the main recent developments regarding managing this infection.
A comprehensive PubMed search was conducted till August 2023 to identify studies on RSV among the adult population. We included observational studies, RCTs on vaccines, and different therapies.
This review should give clinicians an overview of RSV epidemiology and burden among older people and adults with pre-existing risk factors, the most recent randomized clinical trials on RSV vaccines, and the existing data on the different therapeutics existing and under development.
There is a growing body of evidence on RSV burden in adults. The landscape of preventive and curative treatments is quickly evolving.
Respiratory syncytial virus (RSV) is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly. Passive immunoprophylaxis with monoclonal antibody (mAb) ...has been approved to prevent morbidity and mortality from RSV infection in infants. Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion (F) glycoprotein as bait. One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay, and protected mice from RSV infection in vivo. An RV11 escape mutant was identified, which contains an S443P mutation in F protein. Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein. RV11 showed a strong synergistic effect when combined with two RSV antivirals, an F-targeting small molecular inhibitor ziresovir and a site Ø neutralizing mAb D25 (the parental mAb for nirsevimab). The study extended our knowledge to the neutralizing and protective epitopes of RSV, and the mAb RV11 deserves further development for clinical translation.
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•Isolation of human neutralizing antibodies against RSV from the convalescent children.•One potent monoclonal antibody RV11 potently neutralizes both RSV A and B subtypes.•RV11 binds to a conserved epitope across site IV/V site of the fusion glycoprotein in its prefusion state.•RV11 is synergistic with an small molecular inhibitor ziresovir and a site Ø neutralizing mAb.
•Quinoline derivatives have been synthesized as potent antiviral agents.•Molecular docking and dynamics simulation illustrated stable ligand-protein complexes formation of all compounds.•All ...compounds were subjected for broad spectrum antiviral activity.•Antiviral screening showed that compound 4 was active against RSV and compound 6 against YFV.
The designed and synthesized quinoline derivatives were screened for their anti-RSV, anti-YFV and broad spectrum anti-viral activity. Initially, physicochemical and drug-like properties of all compounds were evaluated then molecular docking and molecular dynamics (MD) simulations were performed on the active site of RSV G (glycoproteins) and Mtase (methyltransferase) enzyme against RSV and YFV respectively. All compounds interacted well with amino acid residues Thr173 (2.85 Å), Ser123 (3.02 Å), Gln89 (3.00 Å), Tyr34 (3.62 Å), Val147 (3.08 Å), Leu46 (3.03 Å), Tyr34 (3.62 Å), Trp96 (2.70 Å) of RSV G protein and with amino acid residues Ile124 (2.94 Å), Phe126 (3.08 Å), Tyr89 (3.77 Å), Arg41 (2.91 Å), Arg37 (2.89 Å), Arg84 (2.97 Å) of the MTase protein, showing their nature as probable inhibitors of RSV and YFV. Antiviral screening revealed that compound 4 was an effective inhibitor against RSV, showing an SI value of 11.6 and an EC50 of 8.6 µg/mL (3.2 × 103 µM), while compound 6 was effective against YFV, with an SI value of 28.5 and an EC50 of 3.5 µg/mL (1.17 × 103 µM). Molecular dynamics parameters, such as RMSD, RMSF, and RGyr, were satisfactory for the 6BLH:4 complex, with a predicted binding energy of -5.64 kcal/mol, which was lower than that of the 6BLH: ribavirin complex (-4.13 kcal/mol). Similarly, the MD parameters for the 3EVA:6 complex were also highly satisfactory. Therefore, compounds 4 and 6 may serve as potential inhibitors against RSV and YFV, respectively.
Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and hospitalization in all infants. Many RSV vaccines and monoclonal antibodies (mAb) are currently under development to protect all ...infants, but to date preventive options are available only for preterms. In this study, we assessed the knowledge, attitudes, and practices towards RSV and the preventive use of mAb in a sample of Italian Pediatricians. An internet survey was administered through an internet discussion group, with a response rate of 4.4% over the potential respondents (No. 389 out of 8842, mean age 40.1 ± 9.1 years). The association of individual factors, knowledge, and risk perception status with the attitude towards mAb was initially inquired by means of a chi squared test, and all variables associated with mAb with
< 0.05 were included in a multivariable model calculating correspondent adjusted Odds Ratio (aOR) with 95% confidence intervals (95%CI). Of the participants, 41.9% had managed RSV cases in the previous 5 years, 34.4% had diagnosed RSV cases, and 32.6% required a subsequent hospitalization. However, only 14.4% had previously required mAb as immunoprophylaxis for RSV. Knowledge status was substantially inappropriate (actual estimate 54.0% ± 14.2, potential range 0-100), while the majority of participants acknowledged RSV as a substantial health threat for all infants (84.8%). In multivariable analysis, all these factors were characterized as positive effectors for having prescribed mAb (aOR 6.560, 95%CI 2.904-14.822 for higher knowledge score; aOR 6.579, 95%CI 2.919-14.827 for having a hospital background, and a OR 13.440, 95%CI 3.989; 45.287 for living in Italian Major Islands). In other words, reporting less knowledge gaps, having worked in settings with a higher risk of interaction with more severe cases, and being from Italian Major Islands, were identified as positive effectors for a higher reliance on mAb. However, the significant extent of knowledge gaps highlights the importance of appropriate medical education on RSV, its potential health consequences, and the investigational preventive interventions.
Abstract
Background
Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over ...time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection.
Methods
We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission.
Results
The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6–23 months of age, with an adjusted HR of 3.9 (95% confidence interval CI, 3.1–4.9) for the first 2 years, 2.3 (95% CI, 1.6–3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2–2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0–5 months.
Conclusions
We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6–23 months compared to those whose first severe RSV infection occurred at 0–6 months. This provides new evidence for further assessment of the association and RSV intervention programs.
This correspondence discusses on res awpiratory syncytial virus areness, risk perception and causes. Important limitations and possible furture direction for researching are mentioned.