Abstract Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly ...effective treatment or vaccine is available. To clarify the potential for an anti-G mAb, 131-2G which has both anti-viral and anti-inflammatory effects, to effectively treat RSV disease, we determined the kinetics of its effect compared to the effect of the anti-F mAb, 143-6C on disease in mice. Treatment administered three days after RSV rA2-line19F (r19F) infection showed 131-2G decreased breathing effort, pulmonary mucin levels, weight loss, and pulmonary inflammation earlier and more effectively than treatment with mAb 143-6C. Both mAbs stopped lung virus replication at day 5 post-infection. These data show that, in mice, anti-G protein mAb is superior to treating disease during RSV infection than an anti-F protein mAb similar to Palivizumab. This combination of anti-viral and anti-inflammatory activity makes 131-2G a promising candidate for treating for active human RSV infection.
Respiratory syncytial virus (RSV) and rotavirus infections are long-standing infectious diseases that affect children worldwide. RSV and rotavirus were first discovered in clinical specimens in 1955 ...and 1973, respectively. From their discovery to the present day, significant progress has been made in understanding these two infections. The introduction of a simple and rapid antigen diagnostic test into clinical settings in the 1990s offered new insight into the clinical characteristics and epidemiology of these infections. Regarding therapeutics, symptomatic treatments have remained the mainstay; however, prophylactic humanized anti-RSV monoclonal antibodies have been developed and advances in structural biology may allow for more effective human anti-RSV monoclonal antibodies and novel RSV vaccines to be developed soon. For rotavirus, two vaccines have been licensed and broadly applied over the past 10 years, which have been successful clinically and have changed the epidemiology of rotavirus infections in Japan.
Well-established surveillance and monitoring system for respiratory viruses need be improved and epidemiological data about respiratory viruses is scarce in China. This study aimed to investigate ...epidemiological characteristics of respiratory viruses among hospitalized children ≤ 2 years old with acute respiratory tract infections (ARTIs) in Xiamen, China from October 2014 to September 2017. The clinical records of 7248 children hospitalized for ARTIs were analyzed retrospectively. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children ≤ 2 years old, followed by parainfluenza (5.0%), adenovirus (3.5%) and influenza (1.7%). RSV-infected children possessed a higher disease burden including higher ICU admission rate (12.7%) and hospital charges ($635.36). Especially, infants < 6 months of age had the highest risk of RSV infection (OR= 2.4, 95% CI: 1.9-2.9) and higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital costs ($923.3 vs. $785.5, $811.7) than other age groups. Therefore, infants aged 0-6 months, especially premature infants and children with congenital diseases, should receive more concern. There is an urgent need to develop effective immunization strategies to protect these infants through the first 6 months of life or RSV season.
Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of ...children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases.
Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases.
RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults with pulmonary diseases aged ≥ 60 years. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease.
The COVID-19 pandemic has reinforced an interest in the relationship between air pollution and respiratory viral infections, indicating that their burden can be increased under poor air quality. This ...paper reviews the pathways through which air pollutants can enhance susceptibility to such infections and aggravate their clinical course and outcome. It also summarizes the research exploring the links between various viral infections and exposure to solid and gaseous pollution in Poland, a region characterized by poor air quality, especially during a heating season. The majority of studies focused on concentrations of particulate matter (PM; 86.7%); the other pollutants, i.e., BaP, benzene, CO, NOx, O3, and SO2, were studied less often and sometimes only in the context of a particular infection type. Most research concerned COVID-19, showing that elevated levels of PM and NO2 correlated with higher morbidity and mortality, while increased PM2.5 and benzoapyrene levels were related to worse clinical course and outcome in hospitalized, regardless of age and dominant SARS-CoV-2 variant. PM10 and PM2.5 levels were also associated with the incidence of influenza-like illness and, along with NO2 concentrations, with a higher rate of children's hospitalizations due to lower respiratory tract RSV infections. Higher levels of air pollutants also increased hospitalization due to bronchitis (PM, NOx, and O3) and emergency department admission due to viral croup (PM10, PM2.5, NOx, CO, and benzene). Although the conducted studies imply only correlations and have other limitations, as discussed in the present paper, it appears that improving air quality through reducing combustion processes in energy production in Poland should be perceived as a part of multilayered protection measures against respiratory viral infections, decreasing the healthcare costs of COVID-19, lower tract RSV infections, influenza, and other respiratory viral diseases prevalent between autumn and early spring, in addition to other health and climate benefits.
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•Polluted air may increase the severity of respiratory viral infections.•Poland is a PM and BaP pollution hot spot in Europe.•Air pollution is associated with a higher burden of respiratory viral infections.•Improving the air quality should be a protection measure against infections.•Further studies are encouraged to explore the relationships with other pathogens.
Abstract
Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial ...virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.
•A preventive RSV vaccine for use in infants is an important unmet medical need.•Past studies observed vaccine-associated ERD after RSV infection in RSV-naïve infants.•Risk of vaccine-associated ERD ...has stalled efforts to develop new candidate vaccines.•Understanding the immunopathology of ERD has guided renewed efforts at vaccine development.•This report summarizes presentations and discussion of a recent VRBPAC meeting.
Respiratory syncytial virus (RSV), is a common cause of serious acute lower respiratory tract illness in infants and young children, causing substantial morbidity and mortality globally. Treatment is mainly supportive and currently there is no licensed preventive vaccine. Clinical trials conducted in the 1960s evaluating a formalin-inactivated RSV vaccine (FI-RSV) in RSV-naïve infants resulted in observations of enhanced respiratory disease (ERD) following subsequent natural RSV infection in vaccinees. In these studies, infants immunized with FI-RSV had higher rates of severe RSV disease compared with controls. This outcome redirected focus on identifying the immunologic mechanisms that precipitated ERD as a prerequisite to further vaccine development. Improved understanding of the immunopathogenesis of ERD derived from animal models has stimulated development of new candidate vaccines and engendered discussions among RSV experts about the safety data needed to advance these products into the clinic, and ultimately, into the target population of RSV-naïve infants. The recognition that multiple products would soon be ready for testing in infants and children prompted the FDA to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to seek perspectives and advice of experts regarding the types and extent of preclinical and clinical data that might be needed to support testing in RSV-naïve infants for specific types of candidate RSV vaccines. Committee members agreed that, if certain conditions are met in preclinical and early clinical studies, it would be reasonable to move forward from studies in adults and older children and into clinical trials evaluating vaccine safety and efficacy in RSV-naïve infants. Herein, we review and summarize perspectives on the discussion regarding recommendations for RSV vaccine development in this population.
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children and the elderly, often progressing to pneumonia and severe sequelae. However, there are ...currently no feasible and cost-effective interventions with proven efficacy for children, making medications with anti-RSV activity urgently needed. Traditional Chinese medicine has shown promising therapeutic efficacy in alleviating viral infection symptoms. Therefore, we aimed to develop effective strategies for RSV treatment based on traditional Chinese medicine.
The infection status was assessed in BALB/c mice with or without Xuanfei Formula (XFF) treatment over a one-week period using H&E staining, cytokine assays and RSV titer testing after RSV challenge. Remarkably, on the first day of XFF intervention, both the pro-inflammation cytokine levels in the serum and RSV-N gene copies in the lung of mice were plummeted, compared to the RSV-infected group. This implied that XFF might possess the immune-independent anti-RSV capability. To elucidate the underlying mechanism, we employed transcriptome analysis followed by k-means analysis. The reversal effects of XFF against RSV primarily focused on the processes of innate and adaptive immunity. Additionally, we found that XFF administration corrected the disordered fatty acid and cholesterol metabolism processes during RSV infection. Lipidomics profiling indicated consistent cholesterol abundance with transcriptional changes but not fatty acids. Cholesterol synthesis-related genes mRNA levels and cholesterol synthesis intermediates detection supported XFF's repression upon cholesterol biosynthesis. Aberrantly increased cholesterol production has been reported as necessary for RSV infection. To mimic that, we observed lovastatin treatment inhibited RSV replication and pro-inflammation cytokine expression
. Transcription factor prediction of differentially expressed genes (DEGs) involved in cholesterol synthesis implicated SREBP2. Through network pharmacology, stigmasterol and β-sitosterol were identified as the effective active ingredients within the XFF, with the help of further molecular docking and mass spectrum detection.
experiments demonstrated β-sitosterol and stigmasterol reinforced the bonding between SREBP cleavage-activation protein (SCAP) and insulin-induced gene proteins (INSIGs) to inhibit SREBP2 cleavage maturation and consequent RSV infection.
Xuanfei Formula (XFF) exhibits excellent anti-RSV efficacy by inhibiting SREBP2-mediated cholesterol synthesis to reduce RSV replication and ameliorate inflammation in the lung of infected mice.
Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection among infants and young children worldwide, with seasonal peaks in January and February. This ...study aimed to characterize the RSV samples from a pediatric cohort in the 2021-2022 season in Italy.
In total, 104 samples were collected from pediatric patients attending the "Vittore Buzzi" Children's Hospital in Milan, Italy in the 2021-2022 season. RT-PCR and next-generation sequencing were used to discriminate subgroups and obtain whole genomes. Maximum likelihood and Bayesian phylogenetic methods were used to analyze Italian sequences in the European contest and date Italian clusters.
The median age was 78 days, and 76.9% of subjects required hospitalization, with a higher proportion of patients under 3 months of age. An equal proportion of subgroups A (GA2.3.5) and B (GB5.0.5a) was found, with significant differences in length of hospitalization, days of supplemental oxygen treatment, and intravenous hydration duration. Phylogeny highlighted 26 and 37 clusters containing quite the total of Italian sequences for RSV-A and -B, respectively. Clusters presented a tMRCA between December 2011-February 2017 and May 2014-December 2016 for A and B subgroups, respectively. Compared to European sequences, specific mutations were observed in Italian strains.
These data confirmed a more severe clinical course of RSV-A, particularly in young children. This study permitted the characterization of recent Italian RSV whole genomes, highlighting the peculiar pattern of mutations that needs to be investigated further and monitored.
Abstract
Hospitalizations due to non-coronavirus disease 2019 (non-COVID-19) respiratory illnesses decreased dramatically after social distancing was implemented in a high-risk population in rural ...Alaska; an unprecedented decline compared to the past 10 respiratory seasons. This demonstrates the potential secondary benefits of implementing social distancing and travel restrictions on respiratory illnesses.
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