Search

Federal regulators recently authorised two vaccines designed to prevent infection with respiratory syncytial virus (RSV) for adults aged 60 or older. While some efforts have been made to study vaccine uptake thus far, few have studied this group's intentions to vaccinate, as well as potential barriers to vaccination. This omission is noteworthy as adults aged 60 or older may be at an increased risk of experiencing severe complications from RSV infection. We fielded a nationally representative survey of 1200 US adults (n = 362 aged 60+). Respondents aged 60 or older were asked a series of questions about their willingness to receive an RSV vaccine, vaccine safety, and efficacy attitudes, and their knowledge about vaccination eligibility. We find that a majority of seniors (53%) intend to refuse an RSV vaccine. As of late fall 2023, just 14% of those eligible had already received an RSV vaccine. Multivariate regression models suggest that belief in the safety and efficacy of the RSV vaccine, as well as previous flu and COVID-19 vaccine uptake, are associated with increased RSV vaccination intentions. We document high levels of RSV vaccine hesitancy among adults aged 60 or older and show that negative vaccine attitudes and non-vaccination behaviors motivate RSV vaccine refusal. Our work thereby raises the possibility that efforts to communicate the safety and efficacy of RSV vaccination may have beneficial effects on RSV vaccine uptake. [ABSTRACT FROM AUTHOR]

While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19. [ABSTRACT FROM AUTHOR]

To assess factors associated with the risk of severe disease in children aged 5 years or younger with laboratory-confirmed respiratory syncytial virus (RSV) infection. We conducted a nationwide retrospective cohort study in Mexico. Eligible participants included children aged 5 years or younger with laboratory-confirmed RSV infection January 1, 2023, and May 15, 2024. We collected relevant clinical and epidemiological data. Risk ratios (RR) and 95% confidence intervals (CI) were employed to identify factors associated with the risk of severe disease, characterized by clinical and radiographic evidence of bronchiolitis or pneumonia requiring hospital admission. Data from 2022 children were analyzed and the overall risk of severe disease was 21.0% (n = 424/2022). In multiple generalized linear regression analysis, a personal history of immunosuppression (due to any cause) showed a protective effect (RR = 0.14, 95% CI 0.05–0.42, P = 0.001) against severe RSV disease, while an increased risk was documented for each additional day elapsed between the date of symptom onset and the date of seeking healthcare RR = 1.06, 95% CI 1.02–1.10, P = 0.004). These findings provide insights into risk stratification and suggest specific directions for future research. This information informs the development of targeted intervention strategies to mitigate the impact of RSV infections in this vulnerable population. [ABSTRACT FROM AUTHOR]

With remarkable progress in the field of respiratory syncytial virus (RSV) prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F IgG antibodies across all age groups in Southern China and to evaluate the risk factors associated with lower antibody levels. We performed a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, Southern China, from July 15, 2021, to November 5, 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. The generalized linear models were built to identify factors associated with antibody levels. A total of 890 participants aged 4 months to older than 89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to younger than 2 years (3.0; 95% CI, 2.6–3.5). With increasing age, the RSV pre-F IgG GMT increased to 4.3 (95% CI, 4.1–4.4) between the ages of 2 and younger than 5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.9-fold (95% CI, 0.8–3.6) increase in titre per year before 5 years of age, although it was not significantly associated with antibody levels in adults aged older than 60 years. Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The study aimed to describe respiratory syncytial virus infections among hospitalized adults between January 2021 and February 2023 from a single medical center in Taiwan. Clinical information from infected patients with RSV was via medical charts review. The incidence of RSV during the study period among adult inpatients showed seasonal variation and could be up to around 2 % in peak season. Among 19 patients identified, the major comorbidity was chronic heart disease (10/19; 52.6 %) followed by chronic pulmonary disease (5/19; 26.3 %) and diabetes mellitus (5/19; 26.3 %). A quarter of infected patients required intensive care with overall mortality reached 26.3 % and the readmission rates within 30 days after was 15.8 %. Our study results suggests that RSV infections among adults could cause a substantial disease burden on healthcare systems. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection is an acute respiratory infection caused by RSV. It occurs worldwide, and for over 50 years, several attempts have been made to research and develop vaccines to prevent RSV infection; effective preventive vaccines are eagerly awaited. The RSV fusion (F) protein, which has gained attention as a vaccine antigen, causes a dynamic structural change from the preF to postF state. Therefore, the structural changes in proteins must be regulated to produce a vaccine antigen that can efficiently induce antibodies with high virus-neutralizing activity. We successfully discovered several mutations that stabilized the antigen site Ø in the preF state, trimerized it, and improved the level of protein expression through observation and computational analysis of the RSV-F protein structure and amino acid mutation analysis of RSV strains. The four RSV-F protein mutants that resulted from the combination of these effective mutations stably conserved a wide range of preF- and trimeric preF-specific epitopes with high virus-neutralizing activity. Absorption assay using human serum revealed that mutants constructed bound to antibodies with virus-neutralizing activity that were induced by natural RSV infection, whereas they hardly bound to anti-postF antibodies without virus-neutralizing activity. Furthermore, mouse immunization demonstrated that our constructed mutants induced a high percentage of antibodies that bind to the preF-specific antigen site. These characteristics suggest that the mutants constructed can be superior vaccine antigens from the viewpoint of RSV infection prevention effect and safety. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness and death among children worldwide, particularly in children younger than 6 months and in low-income and middle-income countries. Feasible and cost-effective interventions to prevent RSV disease are not yet widely available, although two new products aimed at preventing RSV disease—long-acting monoclonal antibodies and maternal vaccines—have been licensed within the past 2 years. The primary target of these products is reduction of the substantial burden of RSV-associated acute lower respiratory tract infections (LRTI) in infants younger than 1 year. However, other important public health benefits might also accrue with the prevention of RSV-associated LRTI during the first year of life. Mounting evidence shows that preventing RSV-associated LRTI in infants younger than 1 year could prevent secondary pneumonia caused by other pathogens, reduce recurrent hospitalisations due to other respiratory diseases in later childhood, decrease all-cause infant mortality, ameliorate the burden of respiratory diseases on health-care systems, reduce inappropriate antibiotic use, and possibly improve lung health beyond infancy. We herein review current evidence and suggest approaches to better assess the magnitude of these potential secondary effects of RSV prevention, which, if proven substantial, are likely to be relevant to policy makers in many countries as they consider the use of these new products. [ABSTRACT FROM AUTHOR]

To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9–14 years, 84.6% in those aged 15–24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved. [ABSTRACT FROM AUTHOR]

Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been approved by Health Canada for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract disease. We estimated the health benefits and cost-effectiveness of these vaccines under a publicly funded single-dose vaccination program in Ontario that targets residents of long-term care homes (LTCHs). Additionally, we evaluated an extended program that broadens vaccination to include community-dwelling older adults. A discrete-event simulation model was parameterised with the burden of RSV disease including outpatient care, hospitalisation, and death among adults aged 60 years or older in Ontario, Canada. Accounting for direct and indirect costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained, and determined the range of price-per-dose (PPD) for vaccination programs to be cost-effective from both healthcare and societal perspectives over two RSV seasons. The incremental cost-effectiveness ratio (ICER) was calculated to estimate the additional costs required to gain one QALY. Using a willingness-to-pay of $50,000 per QALY gained, we found that vaccinating 90% of residents in LTCHs with Arexvy would be cost-effective from a societal perspective for a PPD up to $163, producing a mean ICER value of $49,984 (95% CI: $47,539 to $52,704) per QALY gained with a two-year budget impact of $463,468 per 100,000 older adults. The reduction of hospitalizations was estimated at 7.0% compared to the no-vaccination scenario. Extending the program to include community-dwelling older adults with a 74% coverage akin to influenza vaccination, Arexvy remains cost-effective for a PPD up to $139, with a mean ICER value of $49,698 (95% CI: 48,022 to 51,388) per QALY gained and a two-year budget impact of $8.63 million. Compared to the no-vaccination scenario, the extended program resulted in a 57.3% reduction in RSV-related hospitalisations. Vaccinating residents of LTCHs against RSV disease would be cost-effective depending on PPD; extending the program to community-dwelling older adults would provide substantial health benefits, averting significant direct healthcare costs and productivity losses. [ABSTRACT FROM AUTHOR]

The reader will be able to: • Understand the basics of RSV virology. • Recognize the needs and challenges associated with RSV vaccine and monoclonal antibody development in pediatrics. • Gather knowledge on the prevention methods currently available. • Learn about ongoing vaccine clinical trials. Respiratory Syncytial Virus (RSV) is a leading cause of hospitalization in young children and represents a substantial health-care burden around the world. Advances in research have helped identify the prefusion F protein as the key target component in RSV immunization. In this article, we review the previous, current, and ongoing research efforts for immunization against RSV in children. We present the different types of immunization which include monoclonal antibodies, maternal immunization and vaccines while addressing the challenges of preventing RSV infections in the pediatric population. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a frequent cause of acute lower respiratory infection in children, imposing a substantial economic burden on healthcare systems. This systematic review aimed to assess the economic burden and healthcare utilisation of RSV in children aged 0–59 months in Italy. Systematic review. A systematic search of PubMed, Embase, Scopus, and the International HTA Database, including studies published in English or Italian, was conducted between January 2000 and July 2022. Inclusion criteria required studies to be conducted in Italy and provide data on the economic costs and healthcare resource utilisation related to RSV infections. Out of 20,845 records screened, 18 articles met the inclusion criteria. Only one study provided comprehensive data on RSV disease costs, including hospitalisation, diagnostic tests, and medical procedures for infants with RSV-bronchiolitis. The mean cost per inpatient was higher for RSV-positive children (€5753.43 ± €2041.62) than that for RSV-negative children. Additionally, five studies reported a median length of hospital stay of 5 days for RSV-infected children, and four studies indicated a higher frequency of intensive care unit admissions for RSV-infected children than for those with other viral infections. This is the first systematic review to examine the economic burden and healthcare utilisation of RSV in children aged 0–59 months in Italy. While limited data were available, the findings underscore the urgency to conduct further research and gather additional evidence on the costs and healthcare resource utilisation associated with RSV infections. Such efforts are essential for informing the development of effective prevention strategies for paediatric RSV infections in Italy. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus is a leading cause of lower respiratory tract illness globally in children aged <5 years. Each year, approximately 58,000 hospitalizations in the United States are attributed to respiratory syncytial virus. Infants aged ≤6 months experience the most severe morbidity and mortality. Until recently, prevention with the monoclonal antibody, palivizumab, was only offered to infants with high-risk conditions, and treatment primarily consisted of supportive care. Currently, 2 products are approved for the prevention of respiratory syncytial virus in infants. These include the Pfizer bivalent recombinant respiratory syncytial virus prefusion F protein subunit vaccine, administered seasonally to the pregnant person between 32 0/7 and 36 6/7 weeks of gestation, and the monoclonal antibody, nirsevimab, administered to infants aged up to 8 months entering their first respiratory syncytial virus season. With few exceptions, administering both the vaccine to the pregnant person and the monoclonal antibody to the infant is not recommended. All infants should be protected against respiratory syncytial virus using one of these strategies. Key considerations for pregnant individuals include examining available safety and efficacy data, weighing accessibility and availability, and patient preferences for maternal vaccination vs infant monoclonal antibody treatment. It will be critical for maternal–fetal medicine physicians to provide effective and balanced counseling to aid patients in deciding on a personalized approach to the prevention of respiratory syncytial virus in their infants. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

New prevention strategies for respiratory syncytial virus (RSV) are emerging, but it is unclear if they will be cost-effective in low- and middle-income countries. We evaluated the potential impact and cost-effectiveness of two strategies to prevent RSV disease in young children in Vietnam. We used a static cohort model with a finely disaggregated age structure (weeks of age <5 years) to calculate the RSV disease burden in Vietnam, with and without a single dose of maternal vaccine (RSVpreF, Pfizer) or of monoclonal antibody (Nirsevimab, Sanofi, Astra Zeneca). Each strategy was compared to no pharmaceutical intervention, and to each other. We assumed both strategies would be administered year round over a ten-year period. The primary outcome measure was the cost per disability-adjusted life year (DALY) averted, from a societal perspective. We ran probabilistic and deterministic uncertainty analyses. With central input assumptions for RSVpreF vaccine ($25/dose, 69 % efficacy, 6 months protection) and Nirsevimab ($25/dose, 77 % efficacy, 5 months protection), both options had similar cost-effectiveness ($3442 versus $3367 per DALY averted) when compared separately to no pharmaceutical intervention. RSVpreF vaccine had a lower net cost than Nirsevimab (net discounted cost of $213 m versus $264 m) but prevented fewer RSV deaths (24 % versus 31 %). Our results were very sensitive to assumptions about the dose price, efficacy, and duration of protection. At $5/dose and a willingness-to-pay threshold of 0.5 times the national GDP per capita, both prevention strategies have the potential to be cost-effective. RSVpreF vaccine and Nirsevimab may be cost-effective in Vietnam if appropriately priced. [ABSTRACT FROM AUTHOR]

Most respiratory virus surveillance relies on medically attended respiratory illness, but an understanding of the true patterns of infection independent of care-seeking behaviour would enhance clinical and public health responses to respiratory virus outbreaks. We evaluated the potential of decedent surveillance by estimating the burden of respiratory virus infection in decedents in a large, urban medical examiner's office. Observational. In 2020–2022, we tested nasopharyngeal swabs from 4121 decedents in Detroit, Michigan for 15 respiratory viruses, including SARS-CoV-2, respiratory syncytial virus, and influenza virus A and B. We analysed infection prevalence over time and by age, sex, race/ethnicity, and manner of death. Of 4113 valid tests, 30.2% were positive for at least one virus, and 6.1% were positive for multiple viruses. All viruses were detected except for influenza A/H1N1 and influenza B. The most prevalent viruses were SARS-CoV-2 (15.7%), rhinovirus (11.2%), and adenovirus (4.9%), which were detected in all months. Most viruses exhibited decreasing prevalence with age, higher prevalence among Black and Hispanic than among White decedents and lower prevalence among deaths from natural causes; SARS-CoV-2 was a notable exception to the patterns by age and manner of death, instead reflecting community trends in catchment counties. There was high prevalence and diversity of respiratory viruses in decedents entering a large, urban medical examiner's office. Decedent surveillance could offer a clearer picture of the true underlying burden of infection, motivating public health priorities for intervention and vaccine development, and augmenting data for real-time response to respiratory virus outbreaks. [ABSTRACT FROM AUTHOR]

• An association of TNFAIP3-interacting protein 1 (TNIP1) single-nucleotide polymorphisms with human respiratory syncytial virus (HRSV) disease was found. • Rs73272842 G and rs999011 C carriers had lower odds of HRSV disease. • TNIP1 haplotype GC was associated with a lower probability of HRSV disease. • Rs73272842 G and rs999011 C alleles could be protective against HRSV disease. This study analyzed the association of TNFAIP3-interacting protein 1 (TNIP1) polymorphisms with the symptomatic human respiratory syncytial virus (HRSV) infection and bronchiolitis in infants. A case-control study was conducted involving 129 hospitalized infants with symptomatic HRSV infection (case group) and 161 healthy infants (control group) in South Africa (2016-2018). Six TNIP1 polymorphisms (rs869976, rs4958881, rs73272842, rs3792783, rs17728338, and rs999011) were genotyped. Genetic associations were evaluated using logistic regression adjusted by age and gender. Both rs73272842 G and rs999011 C alleles were associated with reduced odds for symptomatic HRSV infection (adjusted odd ratio [aOR] = 0.68 [95% confidence interval {CI} = 0.48-0.96] and aOR = 0.36 [95% CI = 0.19-0.68], respectively] and bronchiolitis (aOR = 0.71 [95% CI = 0.50-1.00] and aOR = 0.38 [95% CI = 0.22-0.66], respectively). The significance of these associations was validated using the BCa Bootstrap method (P <0.05). The haplotype GC (composed of rs73272842 and rs999011) was associated with reduced odds of symptomatic HRSV infection (aOR = 0.53 [95% CI = 0.37-0.77]) and bronchiolitis (aOR = 0.62 [95% CI = 0.46-0.84]), which were validated by the BCa Bootstrap method (P = 0.002 for both). TNIP1 rs73272842 G allele and rs999011 C allele were associated with reduced odds of symptomatic HRSV infection and the development of bronchiolitis in infants, suggesting that TNIP1 polymorphisms could impact susceptibility to HRSV illness. [ABSTRACT FROM AUTHOR]

Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial. To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection. MEDLINE, Embase, and the Institute for Scientific Information Web of Science. Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection. Patients with HM/HSCT. Ribavirin versus no ribavirin. The risk of bias in non-randomized studies of exposure (ROBIN-E). The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence. One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I2 = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I2 = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I2 = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I2 = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I2 = 71% (low certainty of evidence). Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents. [ABSTRACT FROM AUTHOR]

To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes. RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (−0.837; 1.011), −0.10 (−2.171; 1.963), and −1.03 (−4.746; 2.682) log 10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log 10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively. Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. This study is registered with clinicaltrials.gov (NCT03379675). [ABSTRACT FROM AUTHOR]

• The global mortality and disability-adjusted life years (DALYs) rates of respiratory syncytial virus showed a downward trend. • The pace of decline for mortality and DALYs rates was not uniform across age groups. • The mortality is still high in the children under 5 years, which needs more attention. • More attention should be paid to the low Socio-demographic Index area and the elderly over 70 years. Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies. Data on RSV-related burden were extracted from the Global Burden of Disease 2019. Joinpoint regression models were used to assess the global temporal trends of RSV and further stratified analyses were conducted according to the Socio-demographic Index (SDI), which is a composite measure of income, education, and total fertility. Age-period-cohort model was used to evaluate age, period, and cohort effects. In 2019, the global age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASR-DALYs) of RSV were 4.79/100,000 (95% uncertainty interval [95% UI]: 1.82/100,000-9.32/100,000) and 218.34/100,000 (95% UI: 92.06/100,000-376.80/100,000), respectively. The burden of RSV was higher in men than women. The highest ASMR (10.26/100,000, 3.80/100,000-20.16/100,000) and ASR-DALYs (478.71/100,000, 202.40/100,000-840.85/100,000) were reported in low-SDI region. Although mortality and DALYs rates in all age groups declined globally, the pace of decline was not uniform across age groups. Mortality rate in the elderly over 70 years surpassed that in children under 5 years in 2019. This study highlights the need for targeted interventions to reduce the burden of RSV, particularly in low-SDI region, and among the elderly over 70 years. [Display omitted] [ABSTRACT FROM AUTHOR]

• The detection of respiratory syncytial virus (RSV) in infants is significantly associated with illness. • In outpatients aged < 44 years the detection of RSV is associated with illness. • The detection of RSV in HIV-exposed infants is associated with illness. • The point estimate in older adults with severe illness was high but not significant. The detection of respiratory syncytial virus (RSV) in upper airway samples does not necessarily infer causality of illness. We aimed to calculate the attributable fraction (AF) of RSV in clinical syndromes across age groups. Using unconditional logistic regression models, we estimated the AF of RSV-associated influenza-like illness (ILI) and severe acute respiratory illness (SARI) cases by comparing RSV detection prevalence among ILI and SARI cases to those of healthy controls in South Africa, 2012-2016. The analysis, stratified by HIV serostatus, was conducted in the age categories <1, 1-4, 5-24, 25-44, 45-64, and ≥65 years. We included 12,048 individuals: 2687 controls, 5449 ILI cases, and 5449 SARI cases. RSV-AFs for ILI were significant in <1, 1-4, 5-and 24, 25-44-year age groups: 84.9% (95% confidence interval [CI] 69.3-92.6%), 74.6% (95% CI 53.6-86.0%), 60.8% (95% CI 21.4-80.5%) and 64.1% (95% CI 14.9-84.9%), respectively. Similarly, significant RSV-AFs for SARI were 95.3% (95% CI 91.1-97.5) and 83.4% (95% CI 70.9-90.5) in the <1 and 1-4-year age groups respectively. In HIV-infected persons, RSV was significantly associated with ILI cases vs controls in individuals aged 5-44 years. High RSV-AFs in young children confirm RSV detection is associated with severe respiratory illness in South African children, specifically infants. These estimates will assist with refining burden estimates and cost-effectiveness models. [ABSTRACT FROM AUTHOR]

As part of the antiviral response, cells activate the expressions of type I interferons (IFNs) and proinflammatory mediators to control viral spreading. Viral infections can impact DNA integrity; however, how DNA damage repair coordinates antiviral response remains elusive. Here we report Nei-like DNA glycosylase 2 (NEIL2), a transcription-coupled DNA repair protein, actively recognizes the oxidative DNA substrates induced by respiratory syncytial virus (RSV) infection to set the threshold of IFN-β expression. Our results show that NEIL2 antagonizes nuclear factor κB (NF-κB) acting on the IFN-β promoter early after infection, thus limiting gene expression amplified by type I IFNs. Mice lacking Neil2 are far more susceptible to RSV-induced illness with an exuberant expression of proinflammatory genes and tissue damage, and the administration of NEIL2 protein into the airway corrected these defects. These results suggest a safeguarding function of NEIL2 in controlling IFN-β levels against RSV infection. Due to the short- and long-term side effects of type I IFNs applied in antiviral therapy, NEIL2 may provide an alternative not only for ensuring genome fidelity but also for controlling immune responses. [ABSTRACT FROM AUTHOR]

Seasonal influenza vaccine is effective against influenza hospitalisations, but little is known about non-specific effects of the vaccine on other respiratory pathogens with similar seasonal patterns. We aimed to assess the causal impact of seasonal influenza vaccine on laboratory-confirmed hospitalisations for respiratory syncytial virus (RSV) in children using an instrumental variable (IV) strategy. We used probabilistically linked population-based data on childhood immunisations, births, deaths, hospitalisations, perinatal factors, and microbiology test results (2000–2013) of all Western Australian (WA) children born 2000–2012, observed longitudinally until the earliest of 7 years of age or 31 December 2013. We exploited a unique natural experiment created from the WA's state-funded preschool influenza vaccination policy commencing in 2008 and used this as an instrument for children's seasonal influenza vaccination status. We estimated a system of two simultaneous probit equations: determinants of influenza vaccine uptake, and determinants of RSV-confirmed hospitalisation. Influenza vaccine coverage was low prior to 2008 but increased to 36 % in children aged 6–23 months in 2009. The majority (90 %) of RSV-hospitalisations occurred in children <2 years. Receipt of influenza vaccine reduced RSV-hospitalisations, especially in those <2 years with a rate reduction of 2.27 per 1000 (95 % CI: −3.26; −1.28), and a smaller rate reduction of 0.53 per 1000 (95 % CI: −1.04; −0.02) in those 2–7 years. Over the 5-year period (2008–2013), the state-funded preschool-influenza vaccine program resulted in 1,193 fewer RSV-hospitalisations. Of these, 793 (67 %) were in young children <2 years. To our knowledge, this is the first analysis utilising an IV estimation strategy on a population level to assess the causal impact of seasonal influenza vaccine on risk of RSV-hospitalisations. We estimated a small protective effect that warrants further investigation. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients. In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for ≤7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symptoms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function measured by spirometry. Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [−0.43, 0.63] log 10 copies/ml; p = 0.72) or the shorter symptom-duration subgroup (−0.12 [−0.94, 0.69] log 10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated. Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients. [ABSTRACT FROM AUTHOR]

• An overview of the history of treatments for bronchiolitis, including those that failed as well as recent therapies. • To discuss factors that complicated the interpretation of study results, hampered research efforts and current gaps of knowledge. • To highlight those therapies that are accepted for treating bronchiolitis in children. Viral bronchiolitis, which is most commonly caused by an infection with the respiratory syncytial virus (RSV), can lead to respiratory difficulties in young children which may require hospitalization. Despite years of research and medical trials, the mainstay of bronchiolitis treatment remains supportive only. This review provides an overview of the history of different treatments for bronchiolitis, including those that failed, as well as new therapies that are under study. Future studies for the treatment of bronchiolitis should consider different age-groups, important subgroups (i.e., those with a prior history of wheezing, those with a family history of asthma and those with non-RSV viral etiologies) whose response to treatment may differ from that of the composite group. [ABSTRACT FROM AUTHOR]

Respiratory viruses including the respiratory syncytial virus (RSV) aggravate the global burden of virus-inflicted morbidity and mortality. Entry inhibitors are a promising class of antiviral drugs for combating these viruses, as they can prevent infection at the site of viral entry, i.e., the respiratory tract. Here we used a broad-spectrum entry inhibitor, composed of a β-cyclodextrin backbone, functionalized with 11-mercapto-1-undecanesulfonate (CD-MUS) that is capable of neutralizing a variety of viruses that employ heparan sulfate proteoglycans (HSPG) to infect host cells. CD-MUS inactivates viral particles irreversibly by binding to viral attachment proteins through a multivalent binding mechanism. In the present study, we show that CD-MUS is well tolerated when administered to the respiratory tract of mice. Based on this, we developed an inhalable spray-dried powder formulation that fits the size requirements for lung deposition and disperses well upon use with the Cyclops dry powder inhaler (DPI). Using an in vitro dose-response assay, we show that the compound retained its activity against RSV after the spray drying process. Our study sets the stage for further in vivo studies, exploring the efficacy of pulmonary administered CD-MUS in animal models of RSV infection. [Display omitted] • The novel antiviral entry inhibitor CD-MUS is well-tolerated in vivo. • CD-MUS shows suitable pharmacokinetic behavior after pulmonary administration. • CD-MUS can successfully be formulated into an inhalable dry powder formulation. • CD-MUS retains its activity against respiratory syncytial virus after spray drying. • CD-MUS is well dispersed from the Cyclops dry powder inhaler. [ABSTRACT FROM AUTHOR]

• We collected daily data to assess the impact of RSV on infants and caregivers. • RSV quality of life loss was substantial, irrespective of medical attendance. • The quality of life loss in a caregiver trailed that of their infant with RSV. • Costs varied by country and were negligible for non-medically attended RSV. Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs. [ABSTRACT FROM AUTHOR]

Model-based cost-effectiveness analyses on maternal vaccine (MV) and monoclonal antibody (mAb) interventions against respiratory syncytial virus (RSV) use context-specific data and produce varied results. Through model comparison, we aim to characterize RSV cost-effectiveness models and examine drivers for their outputs. We compared 3 static and 2 dynamic models using a common input parameter set for a hypothetical birth cohort of 100 000 infants. Year-round and seasonal programs were evaluated for MV and mAb interventions, using available evidence during the study period (eg, phase III MV and phase IIb mAb efficacy). Three static models estimated comparable medically attended (MA) cases averted versus no intervention (MV, 1019-1073; mAb, 5075-5487), with the year-round MV directly saving ∼€1 million medical and €0.3 million nonmedical costs, while gaining 4 to 5 discounted quality-adjusted life years (QALYs) annually in <1-year-olds, and mAb resulting in €4 million medical and €1.5 million nonmedical cost savings, and 21 to 25 discounted QALYs gained. In contrast, both dynamic models estimated fewer MA cases averted (MV, 402-752; mAb, 3362-4622); one showed an age shift of RSV cases, whereas the other one reported many non-MA symptomatic cases averted, especially by MV (2014). These differences can be explained by model types, assumptions on non-MA burden, and interventions' effectiveness over time. Our static and dynamic models produced overall similar hospitalization and death estimates, but also important differences, especially in non-MA cases averted. Despite the small QALY decrement per non-MA case, their larger number makes them influential for the costs per QALY gained of RSV interventions. • Several static and dynamic cost-effectiveness models for respiratory syncytial virus (RSV) prevention interventions have been published, but these models used context-specific data and produce varied results. • The static and dynamic models produced similar estimated hospitalizations and deaths. The main differences can be explained by (1) model types and structures, (2) assumptions regarding nonmedically attended symptomatic RSV infections, and (3) waning assumptions for maternal vaccine and monoclonal antibody effectiveness. • Nonmedically attended cases' quality-adjusted life-years and waning effectiveness of RSV interventions are influential and uncertain and should be explored in economic evaluations of RSV interventions. [ABSTRACT FROM AUTHOR]

• During the COVID-19 pandemic, infectious disease epidemiology has changed worldwide. • In Japan, 75% of infectious diseases decreased in incidence. • In contrast, 17% of those increased, particularly vector-borne diseases. • Respiratory syncytial virus infection and hand-foot-and-mouth disease showed unique epidemiological changes. • These changes can occur even in countries applying mitigation policies. To elucidate the impact of the COVID-19 pandemic on the epidemiology of other infectious diseases. We investigated the epidemiology of 36 communicable diseases during 2015-2021 in Japan and compared the number of cases in each disease between the prepandemic (2015-2019) and intrapandemic (2020-2021) periods. Relationships between the incidence of the infectious diseases and the COVID-19 pandemic were also investigated. Of 36 communicable diseases, the number of cases in the 27 diseases (75%) mainly caused by pathogens transmitted by droplet or contact was lower intrapandemic than prepandemic, and the cases of 21 diseases (58%) continued to decrease intrapandemic. The number of cases of six diseases (17%) was higher intrapandemic than prepandemic, and the cases of two diseases (5.6%), Japanese spotted fever and syphilis, continued to increase intrapandemic. Time trend analyses revealed a positive correlation between case numbers of communicable diseases and the COVID-19 pandemic, whereas the case numbers of hand-foot-and-mouth disease and respiratory syncytial virus infection rebounded in 2021 after decreasing in 2020. The COVID-19 pandemic has greatly impacted the epidemiology of communicable diseases, suggesting that countermeasures against COVID-19 and lifestyle changes might be involved in these epidemiological changes. [Display omitted] [ABSTRACT FROM AUTHOR]

Pulmonary disorders are exacerbated by high blood sugar, leading to a disordered immune defense and increased susceptibility to infection. Type 2 diabetes mellitus (T2D) is characterized by insulin resistance and inadequate insulin production. Mechanisms leading to pulmonary alternation due to T2D are not clear. The advancements in single-cell RNA sequencing aid in characterizing the effects of T2D on lungs and its altered mechanisms. Our results first revealed that in late-stage diabetic mice, the number of immune cells in the lungs significantly increased, with these immune cells predominantly being immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). At the early stages of diabetes, alveolar cell type I and type II (AT I & II) exhibited a mesenchymal phenotype and showed reduced expression of several key cytokines essential for maintaining lung immunity, including Cxcl15 , Cxcl14 , and Il34. Additionally, the antigen-presenting cell function of AT II, resulting from the downregulation of several MHC type II proteins, was markedly diminished in diabetic mice. Moreover, decreased expressions of interferon-related genes Ifnar1 and Ifnar2 , along with impaired Sftpd expression, compromised lung immunity impairment in diabetic mice. These pathogenic changes contributed to the increased susceptibility and severity of respiratory syncytial virus and tuberculosis in the lung of diabetes. In addition to alveolar cells, pulmonary capillary endothelial cells also exhibited an immature transition phenotype, with a significant increase in angiogenic capacity. Our findings provided a comprehensive exploration of lung pathology under the influence of diabetes and explained the multiple factors impacting lung immunity in diabetic conditions. • Respiratory tract infections by RSV, coronavirus, and Mtb have been linked to T2D with limited information. • In early stage of T2D, a decreased APC function and increased susceptibility to viral and Mtb infection occur in AT II cells. • In late stage of T2D, a dysfunctional PMN-MDSCs of imbalanced IFN-γ/IL-10- signaling contributes to infection. • Further investigation and development of targeted therapy would be required to overcome enhanced infection by T2D. [ABSTRACT FROM AUTHOR]

• The fecal shedding rate of RSV was first measured by detecting RSV RNA in 168 RSV-infected patients. • Distinct patterns of RSV epidemics were found based on wastewater surveillance. • This study filled the gaps of assessment for the suitability of RSV vaccination in the region without clinical surveillance. Respiratory syncytial virus (RSV) represents a significant global health threat, with a disproportionately high disease burden in low and middle-income regions (LMIRs). Estimating the prevalence of RSV infection at the community levels remains a huge challenge, particularly in LMIRs where clinical data are scarce. In this study, we first detected RSV RNA in the fecal samples from 300 patients to understand the fecal shedding patterns of RSV. Meanwhile, we conducted sewage surveillance of RSV in four geographically distinct LMIRs in China from April 2023 to June 2024. Real-time reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR) was employed to monitor the dynamics of sewage RSV concentration in a typical sewershed from Yingkou, Xi'an, Nanchang, and Nanning, respectively. Subsequent amplicon sequencing was conducted to understand the genotype and mutations of sewage RSV. Through RT-qPCR, we observed two RSV epidemics that lasted from late April to May and October to February in both Yingkou and Xi'an. For Nanchang, only one RSV epidemic was observed which emerged from September to February. Notably, in Nanning, a prolonged RSV epidemic was observed from August to April, suggesting RSV vaccination in Nanning faced more challenges. Amplicon sequencing revealed that sewage RSV found in four LMIRs is genetically distinct, highlighting the need for local initiatives for wastewater monitoring of RSV. This study filled the gaps in previous assessment of suitability of RSV vaccination in LMIRs based on clinical surveillance, demonstrating the effectiveness of wastewater surveillance in guiding public health interventions. [ABSTRACT FROM AUTHOR]

Liorice (Glycyrrhiza uralensis Fisch.), a widely used Chinese herbal medicine, is frequently employed in clinical practice to treat viral pneumonia. However, the pharmacodynamic substances and mechanisms of action responsible for its antiviral effects against H1N1 and RSV remain unclear. To investigate the antiviral effects of licorice against H1N1 and RSV. Building on this, we aimed to more comprehensively and accurately identify the pharmacodynamic substances in licorice responsible for its antiviral activity and mechanisms of action against these two viruses. Firstly, the antiviral effects of licorice against H1N1 and RSV were confirmed through in vivo and in vitro experiments. Then, a combination of virus-based affinity ultrafiltration method (VAUM) and serum pharmacochemistry were used to screen for pharmacological substances in licorice and identify their molecular targets against H1N1 and RSV. Results : The in vivo experiments showed that licorice effectively alleviates H1N1 and RSV induced weight loss and lung tissue damage in mice, while also reducing viral loads of H1N1 and RSV in the lungs. Subsequent in vitro experiments confirmed the presence of original compounds in licorice that directly inhibit H1N1 and RSV. By combining both methods, glycyrrhizic acid, glycyrrhetinic acid (GA), isoliquiritigenin (ISL), and glyasperin A (targeting the M2 ion channel) were ultimately identified as the pharmacodynamic substances in licorice responsible for anti-H1N1 activity. Additionally, licochalcone A (LCA) and glyasperin A, which target RSV surface proteins, were identified as the pharmacodynamic substances responsible for anti-RSV activity. Traditional Chinese medicine (TCM) exerts its antiviral effects through a 'multi-component, multi-target' mechanism, which poses challenges for single active compound screening methods to adequately address. By integrating VAUM and serum pharmacochemistry for the first time, one approach focused on identifying compounds in TCM that directly bind to viral surface proteins, while the other targeted compounds that enter the bloodstream in their original form and exhibit antiviral activity. This provides a novel approach for studying the pharmacodynamic substances of antiviral effects in TCM. [Display omitted] • The anti-H1N1/RSV effect of licorice were confirmed. • The VAUM, crucial for screening antiviral compounds in TCM, was developed. • VAUM and serum pharmacochemistry were first combined to identify antiviral compounds in TCM. • Combining these two methods overcomes the limitations of each individually. • Five compounds were identified as licorice's pharmacological substances against H1N1 and RSV. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is increasingly a recognized cause of severe respiratory infection among adults. This retrospective observational study compared the costs of RSV and influenza hospitalizations in adults aged ≥18 years admitted to the Spanish National Healthcare System between 2016 and 2019. Mean costs per hospitalization episode were compared using a multivariable log-gamma generalized linear model adjusted by age, risk group and calendar year. Total annual hospitalization costs were estimated from population incidence rates (for RSV we used model-based rates reported in a published study due to the substantial under-ascertainment of cases) and the mean cost per episode. ICD-10 codes identified a total of 11,662 adults hospitalized with RSV and 79,319 with influenza. The mean length of stay was longer for RSV than for influenza in low-risk patients aged 60–79 years, moderate-risk patients (those with chronic medical conditions) aged ≥50 years and in high-risk (those with immunocompromising conditions) patients aged <80 years. There were no differences in intensive care unit (ICU) admission (except for higher admission in high-risk RSV patients aged 70–79 years), ICU stay or in-hospital case fatality rate. Mean costs per hospitalization episode were also similar: RSV €3870 (95 % CI 3773–3942) vs influenza €3888 (95 % CI 3836–3931). Total annual costs for RSV-attributable hospitalizations were estimated at M€194, twice than that of influenza (M€83). Annual costs increased by 11 % over the study period for RSV and by 47 % for influenza. In 2019, adults aged ≥60 years and ≥ 70 years contributed 91 % and 82 %, respectively, of the total RSV-attributable hospitalization costs in adults. RSV has a significant economic burden to the Spanish National Healthcare System, likely greater than influenza. Efficacious RSV vaccines and antivirals have the potential for high public health impact. • Mean adjusted costs per hospitalization episode were similar for RSV and influenza. • Annual RSV-attributed costs (M€194.3) were higher than costs of influenza (M€83.2). • Adults aged ≥80 years accounted for 44 % of all RSV hospitalization costs. • RSV-attributed costs increased by 11 % and influenza costs by 47 % from 2016 to 2019. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a major cause of respiratory illness, with younger infants at greatest risk of hospitalisation. With the recent approval of a maternal RSV vaccine in Australia, it is timely to evaluate its potential costs and health benefits in Australia. We applied an integrated dynamic and economic evaluation model to estimate specific outcomes of RSV disease and the cost-effectiveness of a year-round maternal RSV vaccination program in Australia. Cost-effectiveness was estimated using the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained. From a healthcare system perspective, the maternal vaccination program was estimated to be cost-effective at a vaccine price less than approximately 120 Australian dollars ($AU), assuming a willingness-to-pay (WTP) threshold of $AU 50,000/QALY gained. Most of the estimated cost-savings were from preventing RSV hospitalisations in infants aged <6 months. However, while 82% of the cost-savings were from preventing RSV hospitalisations in infants aged <6 months, only about 25% of the QALY gains were in this age group. The majority of the other QALY gains came via herd effects from prevention of death in older adults and to a lesser extent, prevention of nonmedically-attended illness in older teens and adults. When predicted cost-savings and QALY gains in those ≥6 months of age were excluded, the vaccine price required to meet the assumed WTP threshold fell to $AU 63. A maternal RSV vaccination program in Australia could provide value for money by reducing hospitalisations and associated costs among infants aged <6 months, depending on the vaccine price. We have provided evidence that herd effects beyond the target population may be an important consideration in assessing cost-effectiveness of maternal RSV vaccination. [ABSTRACT FROM AUTHOR]

Kemin capsule (KMC), as an innovative traditional Chinese medicine (TCM), has shown excellent efficacy in treating PIC in China. The post-infectious cough (PIC) is a common condition in pediatrics, and the inflammatory responses to PIC are intricately linked to the immune mechanisms of the host. However, the precise mechanisms involved remain uncertain. The objective of this research is to investigate the mechanisms by which KMC treats PIC using a combination of UPLC-MS, bioinformatics, network pharmacology, and molecular docking. The study's findings will be corroborated through in vitro and in vivo experiments. This study identified the main components of KMC using UPLC-MS. The mechanism by which these capsules treat PIC was explored through transcriptomics, network pharmacology, and molecular docking. PIC model in Balb/c mice was induced with respiratory syncytial virus (RSV) at a titer of 10^5.5 TCID 50 /mL. From day 14 post-infection, the mice were orally administered the capsules at doses of 0.3, 0.6, and 1.2 g/kg for two weeks. Cough was stimulated with capsaicin at 10^-4 mol/mL, and the effects on PIC mice were measured by cough frequency, latency, ELISA, and H&E staining. Expression levels of transient receptor potential (TRP) channel proteins and the PI3K/AKT signaling pathway were analyzed using RT-qPCR, immunohistochemistry (IHC), and western blot (WB). The effect of KMC on A549 cells proliferation in vitro was also assessed. The therapeutic efficacy of KMC is potentially exerted through its inherent bioactive constituents, including deoxyandrographolide, quercetin, and chryseriol. These compounds are hypothesized to modulate the PI3K/AKT signaling pathway and influence the function of TRP channel proteins, consequently mitigating the pathological state associated with PIC. In vivo experiments have demonstrated that KMC significantly reduces the frequency of coughs and extends the cough latency period in mice with PIC. KMC mitigates airway inflammation by suppressing the production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. The expression or phosphorylation levels of key regulators in the PI3K/AKT/TRP axis in mouse lung tissue, including PI3K, AKT, NF-κB p65, TLR4, STAT3, TRPV1, TRPA1 were significantly reduced. KMC exerts its therapeutic effect on PIC by dampening the activation of the PI3K/AKT signaling pathway and the activity of TRPA1 and TRPV1 ion channels. [Display omitted] • Identification of 57 components in KMC via UPLC-Q-Exactive-MS. • Mechanisms of KMC's efficacy in PIC elucidated by various bioinformatics methods. • Molecular docking confirms binding affinity of KMC components with gene targets. • In vitro and in vivo experimental validation of mechanisms. • The PI3K/AKT signaling pathway and TRPA1/TRPV1 channels play significant roles. [ABSTRACT FROM AUTHOR]

• An oral vaccine based on adenoviral vector. • Oral vaccines provide effective protection against RSV infection in mice. • Oral vaccination elicited a robust antibody response, T-cell response, and B-cell response. • dsRNA adjuvants significantly enhanced T-cell immune responses. A safe and effective vaccine is urgently needed to prevent acute respiratory infections caused by respiratory syncytial virus (RSV). Oral administration offers several advantages, including ease of delivery, minimal stress for vaccine recipients, and greater safety than the systemic injection. In this study, we developed an oral vaccine candidate based on the human adenovirus serotype 5 (Ad5) vector, Ad5-PreF-DS2, encoding a prefusion protein of RSV with a dsRNA as an endogenous adjuvant. We evaluated the immunogenicity and protective efficacy of oral immunization against an RSV challenge in mice, comparing it with those of IM and IN immunizations. Subsequently, we performed an in-depth analysis of the B cell immune response to the oral vaccine. Our findings indicate that oral vaccines elicited a robust antibody response, T-cell response, and B-cell response, and provide effective protection against RSV infection in mice. Importantly, dsRNA adjuvants significantly enhanced T-cell immune responses and increased neutralizing antibody levels when administered via oral vaccination (P < 0.05). These preclinical data demonstrate the capacity of an oral vaccine to induce protective immunity against RSV and support further development of RSV vaccine. [ABSTRACT FROM AUTHOR]

Our study aimed to assess parents' perceptions of respiratory syncytial virus (RSV) and their attitudes towards the RSV vaccine in China. The cross-section study was performed between August 21 and November 15, 2023, in Jiangsu province, eastern China. We collected socio-demographics, awareness, knowledge, perceptions of susceptibility and severity of RSV, and attitudes towards RSV vaccine using online survey questionnaire from parents of child aged ≤14 years old. The chi-square test and logistic regression model to explore the associated factors. A total of 2135 participants were included. About 26.0 % indicated that they had never heard of RSV (556/2135) and were unaware that infants and young children are at a high risk of contracting RSV (557/2135). The proportion of parents with a child under 1 year of age who were unaware of RSV was notably higher than that of parents with children in other age groups. 42.9 % of parents (916/2135) showed low level of perceived susceptibility of contacting RSV infection for their child. 70.6 % of parents (1508/2135) expressed their willingness to vaccinate their child against RSV. The most common reason for refusing the RSV vaccine was "Concern about vaccine's safety or side effects." 60.8 % of participants (1299/2135) considered a price of the RSV vaccine below 200 CNY (28 USD) as acceptable. The parents, particularly those with younger children, exhibited limited awareness and knowledge regarding RSV infection. Our study also showed the potential role of vaccine price as a barrier to the future use of RSV vaccine in China. • There was 26.0 % of parents reporting that they never heard of RSV. • 70.6 % of parents were willing to vaccinate against RSV for child. • Vaccine's safety or side effects concerns was the most common reason for refusing. • 60.8 % of parents considered a price of vaccine below 200 CNY as acceptable. [ABSTRACT FROM AUTHOR]

This retrospective observational study aimed to quantify the costs associated with hospitalized respiratory syncytial virus (RSV) in children <18 years admitted to the Spanish National Healthcare System between 2016 and 2019 and contrast them with the costs of unspecified bronchiolitis/bronchitis/pneumonia (UBP) and influenza. The mean cost per hospitalization episode was reported by age group, risk category and prematurity. Total annual hospitalization costs were calculated from population incidence rates and the mean cost per episode. A total of 41,934 children were hospitalized with RSV, 70,160 with UBP and 8525 with influenza during 2016–2019. The highest incidence of hospitalization for RSV, UBP, and influenza occurred among infants <6 months. The mean cost per episode was highest for RSV cases aged <6 months with at least one risk factor (€4760 high vs €2827 low risk), while the mean cost ranged from €3704–4352 for high-risk and €2687–3475 for low-risk children of other ages, and from €4300–44,594 for preterm infants. In the 0–5 months age group, the mean cost per episode for UBP was €4189 and €2666 for high and low risk, and for influenza it was €3134 and €2081, respectively; while the mean cost of co-infected RSV-influenza cases was €4809 and €2887, respectively. The mean total annual estimated cost for RSV for children aged 0–17 years was €39.3 M based only on reported cases, rising to €53.8 M if we correct for under-diagnosis and all RSV-attributable cases are considered. In contrast, the mean total annual cost for influenza was €5.9 M. Compared to influenza, RSV has a substantially higher economic burden; nevertheless, the Spanish immunization schedule recommends influenza vaccine between 6 and 59 months of age and RSV monoclonal antibody only for those aged <6 months. RSV immunization is still to be implemented in older children, considering that 37 % of RSV hospitalized patients were aged ≥6 months. • Infants <6 months showed the highest incidence of hospitalization. • Infants <6 months accounted for 63 % of all RSV hospitalization costs. • The hospitalization cost of RSV was higher than that of influenza. • Total hospitalization costs for RSV increased from 2016 to 2019. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease. This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18–59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants. 1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18–59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18–59-years than adults ≥65 years. Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18–59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. www.clinicaltrials.gov NCT05070546 • Immune responses to Ad26/protein preF RSV were noninferior in adults aged 18–59 vs ≥65-years. • Immune responses were non-inferior in high-risk adults aged 18–59-years vs ≥65 years. • Efficacy in high-risk adults aged <60 years can be inferred from demonstrated efficacy in those aged ≥65 years. • Safety and reactogenicity were clinically acceptable. • Reactogenicity was markedly age-dependent, decreasing with age. [ABSTRACT FROM AUTHOR]

Test-negative design (TND) studies are cornerstones of vaccine effectiveness (VE) monitoring for influenza. The introduction of SARS-CoV-2 and RSV vaccines complicate the analysis of this design, with control selection restriction based on other pathogen diagnosis proposed as a solution. We conducted a simulation study and secondary analysis of 2017–18 and 2018–19 TND estimates from a Southeast Michigan ambulatory population to evaluate RSV-status-based control restriction. Simulations suggest that with vaccine-preventable RSV, influenza VE could be moderately biased with RSV prevalence ≥25 % of controls. Real-world analysis showed 151 influenza-negative adults (10.4 %) had RSV detected from the enrollment nasal swab. There were minimal differences in results of adjusted models with or without RSV exclusion from control groups. Findings suggest that inclusion of RSV cases in the control group of TND studies for influenza VE, particularly where RSV is not vaccine preventable, does not currently pose a major concern for bias in VE estimates. [ABSTRACT FROM AUTHOR]

In this short communication, we describe annual accident and emergency (A&E) respiratory illness attendances in English hospitals for the years 2017–2019 estimated to be attributed to respiratory syncytial virus (RSV) in adults aged ≥18 years. Results suggest RSV caused an overall annual average of 23,440 adult A&E respiratory attendances in England across this period, equating to 53 A&E adult respiratory attendances per 100,000 population per year. Adult respiratory A&E attendance due to RSV increased with age and was highest in older adults, especially those aged ≥75 years where RSV was estimated to cause an average of 238 respiratory attendances per 100,000 population per year. However, this may be under an under ascertainment as respiratory attendances only were included. A further proportion of adult A&E attendances due to cardiac events such as myocardial infarction (MI), arrhythmias and ischemic stroke (IS) may be attributed to an RSV infection, particularly in older adults. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV. Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period. In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified. MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases. Trial Registration: Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022). [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among infants. A maternal RSV vaccine that protects young infants has recently been approved for registration in Australia. We estimated the population benefits of a future year-round maternal RSV vaccination program in terms of prevented RSV infections and hospitalisations in Australia. We described RSV transmission using an age-structured compartmental model calibrated to Australian aggregated monthly RSV-coded hospitalisations in children aged <5 years. We accounted for mother and infant interactions in the model to capture herd effects more realistically. Using the model, we estimated the annual age-specific RSV infections and hospitalisations prevented for a range of assumptions for vaccine efficacy, coverage, and durability to estimate the future impact of year-round maternal RSV vaccination on infants and the wider population. Assuming base case vaccine efficacy, 6 months duration of protection and 70% coverage, RSV hospitalisations were predicted to fall by 60% (from 3.0 to 1.2 per 100 persons) in infants aged <3 months and 40% (from 1.9 to 1.1 per 100 persons) in 3–5-month-olds. These benefits were primarily due to direct protection to infants of vaccinated mothers. This vaccine program was predicted to reduce the population-level RSV infection by about 4%. Coverage and duration assumptions were influential, with higher coverage leading to larger declines in infants <6 months, and increased duration of protection leading to additional declines in infection and hospitalisation risk in older infants aged 6–8 months. With vaccine uptake similar to that achieved for other maternal vaccines in Australia, a year-round RSV maternal vaccination program is predicted to approximately halve the number of RSV hospitalisations in infants younger than 6 months. There was a small herd effect predicted in the base case but potential for larger benefits if vaccine coverage or the duration of protection exceeds base case assumptions. [ABSTRACT FROM AUTHOR]

We report a two-year-old girl whose progressive lower extremity weakness was masked by a respiratory presentation, only to be identified as having Guillain-Barré syndrome in the context of respiratory syncytial virus bronchiolitis. This case adds to the expanding literature of postinfectious demyelinating disorders in very young children, which seem to be unrelated to particular antigenic triggers. [ABSTRACT FROM AUTHOR]

• Respiratory syncytial virus is the leading cause of hospitalization among infants aged under 12 months. • Age-specific risk of respiratory syncytial virus–associated hospitalizations in Japan was investigated. • The hospitalization risk during primary infection was highest in infants. • The relative risk of hospitalization owing to secondary infection was small. Elucidating the infection dynamics that lead to severe respiratory syncytial virus (RSV) pneumonia and hospitalization among young children are critical. We explored the role of infection parity as well as age in months for RSV-associated hospitalization among young children in Japan. We used a sequential transmission catalytic model to capture the transmission mechanisms of RSV among infants in an endemic state. We investigated data on the age-dependent seroprevalence and incidence rate of hospitalization in Japan, and jointly estimated the age-specific risk of hospitalization during primary RSV infection and relative risk of hospitalization during secondary infection in children aged <5 years. The estimated risk of hospitalization with primary infection was 0.08 (95% CI: 0.05-0.14) in infants aged 0-2 months. The estimated relative risk of hospitalization owing to secondary infection was 0.18 (95% CI: 0.01-2.04). Our simple models successfully captured the infection dynamics of RSV among young children in Japan. The age group of early infancy may be most vulnerable to infection and hospitalization, offering key insights into future vaccinations. The burden of hospitalization from secondary infection may be less important in young children. [ABSTRACT FROM AUTHOR]

• Respiratory syncytial virus (RSV) remains a leading cause of medically-attended (MA) lower respiratory tract infection (LRTI) and non-LRTI episodes in the US in infants and children. • The vast majority (>80 %) of medically-attended RSV LRTIs and non-LRTIs occur among healthy full-term infants. • The long-acting mAb intervention is the most effective at reducing the number of MA-RSV episodes, especially in older infants (≥6 months old). • Our model is unique in simultaneously accounting for gestational age at birth, birth month, and RSV seasonality. Respiratory syncytial virus (RSV) remains a leading cause of medically-attended acute respiratory infection in infants and children. With multiple preventative interventions under development, accurate estimates of health care resource utilization are essential for policy decision making. We developed a literature-based decision-tree model that estimated annual medically-attended RSV (MA-RSV) lower respiratory tract infection (LRTI) and non-LRTI episodes in the US for all infants and for high-risk toddlers. The model accounted for the gestational age and birth-month of infants, and the seasonal variation in RSV incidence. The impact of no prophylaxis, palivizumab, maternal vaccine, and long-acting monoclonal antibody (mAb) interventions was estimated. We estimated 1.23 million (range: 0.96 million–1.40 million) annual MA-RSV LRTI/non-LRTI episodes comprised of 1.19 million (range: 0.93 million–1.36 million) emergency department (ED) and outpatient visits, and 39,040 (range: 32,726–45,851) hospitalizations. Outpatient and ED visits were comprised of 586,034 (range: 430,595–718,868) LRTIs and 608,733 (range: 495,705–644,658) non-LRTIs. The long-acting mAb intervention resulted in the greatest number of averted outpatient and ED episodes (310,997 [53%] LRTIs; 284,305 [47%] non-LRTIs) and hospitalizations (21,845 [56%]). Full-term infants constitute the highest proportion of episodes across all interventions. MA-RSV disease is substantial in infants and high-risk toddlers. Long-acting mAbs are most effective at reducing the number of MA-RSV LRTI/non-LRTI episodes, and the only intervention that prevents disease in older infants (≥6 months old). [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the survival experience of children hospitalized with laboratory-confirmed respiratory syncytial virus (RSV) infection due to bronchiolitis. This was a nationwide retrospective cohort study conducted in Mexico. We analyzed data from 436 children aged 5 years and younger, with symptom onset between August 2021 and November 2022. The Kaplan–Meier method was used to compute survivor functions and their 95% confidence intervals (CI). High survival rates were observed, particularly within the first three weeks of hospital admission. The 3-day survival rate was 99.8% (CI 98.4–99.9%), which decreased to 98.9% (CI 96.5–99.7%), 97.5% (CI 91.9–99.3%), 86.7% (CI 48.2–97.2%), and 69.4% (CI 24.2–91.0%) on days 7, 14, 21, and 28 of hospital stay, respectively. We documented a total of 5 fatal outcomes, resulting in a mortality rate of 2.1 (95% CI 0.9–5.1) per 1,000 person-days. Our study analyzed a large cohort of pediatric patients with bronchiolitis caused by RSV infection, providing valuable insights into the in-hospital progression of this disease. [ABSTRACT FROM AUTHOR]

• Clinicians were only moderately knowledgeable about RSV infections in adults. • Healthcare organizations lack standards for tracking adult RSV testing/treatment. • Clinicians responded positively about the idea of a new RSV vaccine for adults. [ABSTRACT FROM AUTHOR]