Respiratory Syncytial Virus Infection Research Articles

Exploring Risk Factors Associated With Intensive Care Unit Admission in a Retrospective Cohort of 631 Children With Bronchiolitis.

Examine the trends and epidemiological features of acute hospitalized bronchiolitis cases among children aged 28 days to 2 years, both before and after the COVID-19 pandemic. Furthermore, evaluate their need for intensive care unit (ICU) admission and identify primary risk factors associated with severe bronchiolitis. A retrospective analysis was conducted on the medical records of paediatric patients admitted to Meyer Children's Hospital in Florence (Italy) from September 2019 to March 2023, with the diagnosis of bronchiolitis. Between 2019 and 2023, bronchiolitis hospitalizations grew by 76%, going from 131 to 230 cases, after the historical minimum of 14 cases in the 2020-2021 season. Respiratory syncytial virus (RSV) infection emerged as the predominant etiological agent, contributing to 76% of hospitalizations in both 2021-2022 and 2022-2023 seasons. Coinfection cases increased fivefold from 2019 to 2023, accounting for 23% of hospitalizations in 2022-2023. In addition, the ICU admission rate increased from 13% in 2019-2020 to 31% of bronchiolitis hospitalizations in 2022-2023. Univariate and multivariate analysis data show that infants below 2 months of age, preterm births, comorbidities and RSV infections were correlated with a higher risk for ICU admission. The growing trend in ICU admissions for acute bronchiolitis in hospitalized children represents a substantial health challenge. Addressing the bronchiolitis epidemic necessitates a strategic focus on RSV prevention through interventions such as vaccines and monoclonal antibodies. Urgent implementation of preventive initiatives, together with continuous surveillance and the establishment of national databases, is imperative and cannot be further deferred.

Characteristics of the respiratory season in 2022—23 and 2023—24 according to data from the city children's hospital

The end of the COVID-19 pandemic in the respiratory disease season of 2022—23 was characterized by an increase in the number of cases, a shift in the classic peaks of morbidity for various infections, and a predominance of influenza and respiratory syncytial virus infection (RSVI). Materials and methods. When compared with the last pandemic season, a later start of the 2023—24 respiratory season was noted with a gradual shift to the usual pre-pandemic period timing of viral morbidity increases. Results. The currently prevailing SARS-CoV-2 Omicron variant has acquired the properties of a common respiratory viral infection, currently all-season, with a mild course, without the need for hospitalization. The number of patients with influenza has decreased and there were no patients with a severe course of this infection. A feature of the first post-pandemic season was the outbreak of mycoplasma infection, which was a reason of large number of pneumonia cases.

Burden of Respiratory Syncytial Virus-Associated Hospitalizations in US Adults, October 2016 to September 2023.

Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

Immune Responses to Respiratory Syncytial Virus Vaccines: Advances and Challenges

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

Observational Study on the Clinical Reality of Community-Acquired Respiratory Virus Infections in Adults and Older Individuals

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

Burden of Respiratory Syncytial Virus Infection in Children and Older Patients Hospitalized with Asthma: A Seven-Year Longitudinal Population-Based Study in Spain

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

Nationwide Epidemiology and Outpatient Healthcare Resource Use of Children with Respiratory Syncytial Virus from 2005 to 2021.

Respiratory syncytial virus (RSV) poses a global health challenge, particularly among younger children. While the disease burden in Japan has been preliminarily quantified in short-term or inpatient settings, a comprehensive understanding of outpatient settings at a national level is still lacking. In this retrospective cohort study, we followed 697,802 children until they reached 60 months of age, amounting to 25,680,468 million person-months, using two nationally representative databases from the fiscal years 2005-2021. We analyzed trends in the epidemiology of RSV infections and associated outpatient health resource use. Incidence rates of RSV and associated hospitalizations among infants showed fluctuations of 50-100 cases and 20-30 hospitalizations per 1000 person-years, respectively, during the 2010s. These rates dropped to 8.7 cases and 2.2 hospitalizations per 1000 person-years in 2020, then returned to the same levels in the 2010s. Similar patterns were noted for RSV testing, outpatient visits, healthcare cost and the proportion of cases hospitalized (case-hospitalization risk). Whereas antibiotic use decreased from 56.4% in 2005 to 27.8% in 2021, palivizumab use increased from 95.2-195.9 days of therapy per 1000 person-years. Applying the calculated incidence rates to national data, annual outpatient healthcare costs for RSV infections were estimated to be 7-9 billion JPY (50-64 million USD) for children aged <60 months in the late 2010s. Our study highlights the changes in epidemiology and outpatient health resource utilization for children with RSV infections. These findings are valuable for policymakers and clinicians aiming to develop strategies, including newly developed maternal vaccines and single-dose long-acting monoclonal antibodies.

Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose-response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.IMPORTANCEA significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both in vitro and in vivo and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.

Respiratory Syncytial Virus associated hospitalisations in children up to 6 years of age in Italy: a systematic review.

Respiratory syncytial virus is a leading cause of respiratory hospitalisations in infants. This systematic review (registration number: CRD42021248309) aims to synthesise the available evidence on Respiratory Syncytial Virus-related hospitalisations among children aged 0 to 6 years in Italy. The literature search was conducted on PubMed, Embase, Scopus, and International HTA, covering the period from January 2000 to July 2022, with a focus on studies that reported information on Respiratory Syncytial Virus-associated hospitalisation in children aged 0-6 years in Italy. Eight articles were included after screening 20,845 records. These retrospective studies reported that most hospitalisations were among those <1 year (71.5%-88.8%), infants aged <1 year were also at higher risk of hospitalisation in intensive care unit. Respiratory Syncytial Virus infections typically peaked December-February, with an atypical early start in August 2021. Subtype analysis showed alternating prevalence of Respiratory Syncytial Virus-A and Respiratory Syncytial Virus-B across different seasons. Coinfections were not uncommon (1.1%-37.4%), with rhinovirus and bocavirus being the most frequent. All infants at their first Respiratory Syncytial Virus season showed an increased risk of severe infection and hospitalisation, regardless of the gestational age at birth, compared to older participants. This systematic review will enrich the understanding about Respiratory Syncytial Virus disease and help support decisions regarding prevention efforts in Italy.

Landscape of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirusgenus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.

Impact of Respiratory Syncytial Virus (RSV) in Adults 60 Years and Older in Spain

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

The levels and clinical significance of serum miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia

To investigate the levels and clinical significance of serum microRNA (miR)-146a, miR-145, T-helpertype17 (Th17)/regulatory T cell (Treg) in children with respiratory syncytial virus (RSV) infectious pneumonia. The clinical data of 200 children with RSV infectious pneumonia admitted to Nantong Maternal and Child Health Hospital from June 2020 to June 2023 were retrospectively collected as the study group. At the same time, 200 children with mycoplasma pneumonia were selected as the common pneumonia group and 200 healthy children were selected as the healthy group. The levels of serum inflammatory factors [interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)] were detected by enzyme-linked immunosorbent assay. The expression levels of serum miR-146a and miR-145 were detected by RT-qPCR. The levels of Th17/Treg were detected by flow cytometry. The levels of miR-146a, miR-145, Th17/Treg and serum inflammatory factors were compared among the three groups. Pearson method was used to analyze the correlation between miR-146a, miR-145, Th17/Treg and serum inflammatory factors in children with RSV infectious pneumonia. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia. The results showed that in the study group, miR-146a (2.01±0.58), miR-145 (1.81±0.46), Th17/Treg (1.09±0.31), IL-6 (7.82±2.11) ng/L and TNF-α (9.82±2.96) ng/L were higher than those in the common pneumonia group miR-146a (1.49±0.42), miR-145 (1.43±0.31), Th17/Treg (0.77±0.24), IL-6 (5.89±1.32) ng/L, TNF-α (7.34±2.32) ng/L and healthy group miR-146a (1.25±0.19), miR-145 (1.19±0.16), Th17/Treg (0.38±0.09), IL-6 (4.52±1.04) ng/L, TNF-α (5.39±1.07)ng/L. The levels of the above indexes in the common pneumonia group were higher than those in the healthy group, and the differences were statistically significant (F=183.543, 175.938, 617.182, 226.657, 193.459, P<0.05). In the study group, IFN-γ (14.18±3.25) pg/ml was lower than that in the control group (19.52±5.13) pg/ml, but higher than that in the healthy group (9.77±2.40) pg/ml, and the difference was statistically significant (F=335.432, P<0.05). Pearson correlation analysis showed that miR-146a, miR-145 and Th17/Treg were positively correlated with IL-6 and TNF-α (P<0.05), but negatively correlated with IFN-γ (P<0.05). ROC curve results showed that the area under the curve (AUC) of miR-146a, miR-145 and Th17/Treg in the diagnosis of RSV infectious pneumonia was 0.767, 0.762 and 0.790, respectively, while the combined detection of the three was 0.904. In conclusion, the levels of miR-146a, miR-145 and Th17/Treg are highly expressed in children with RSV infectious pneumonia, and are closely related to the inflammatory response of children. The combined detection of the three may have certain application value in the auxiliary diagnosis of RSV infectious pneumonia.

Lethal model for respiratory syncytial virus infection using C57BL/6 mice.

A mouse model of respiratory syncytial virus (RSV) infection is useful for fundamental research aimed at developing antiviral drugs. Previous mouse models of RSV infection were unable to adequately mimic the pathophysiology of human patients due to the low amplification efficiency of this virus in the mouse lung. Furthermore, mice other than BALB/C mice are difficult to use for the RSV infectious model. We established a new mouse-adapted RSV strain, MP11. The MP11 virus can cause severe pneumonia in C57BL/6 mice and efficiently replicate and induce inflammation in the lung. Therefore, C57BL/6 mice can be used for RSV infection experiments using MP11 virus. We established a reverse genetics system for the MP11 virus using our mouse model. This system enables detailed analyses of the MP11 virus, such as functional analysis of each viral protein. Our study provides techniques that can advance fundamental research in elucidating the pathogenesis of RSV infections.

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Profile of Children Admitted with Respiratory Syncytial Virus Infections in a Quaternary Care Hospital in Kerala, India

Profile of Children Admitted with Respiratory Syncytial Virus Infections in a Quaternary Care Hospital in Kerala, India

An Overview on Disease Burden and Management of Respiratory Syncytial Virus Infections in Older Adults in the Asia-Pacific Region.

Respiratory syncytial virus (RSV) represents a significant burden on older adults (aged ≥ 50years) globally and can lead to acute respiratory tract infections with substantial morbidity and mortality. However, there is a significant gap in knowledge regarding RSV infection in older adults, particularly in the Asia-Pacific region. This knowledge gap underscores the need for targeted and comprehensive studies to fully understand the nuanced epidemiology of RSV in ageing populations. This review synthesises data from various countries, emphasising the impact of RSV on older populations in the Asia-Pacific region. The overall proportions of RSV-related ARIs among older patients ranged from 0.2% to 5.6%. Among older adult patients with CAP, RSV accounted for 1.1%-10.3% of cases. However, it is crucial to note that the diversity in reported percentages highlights the influence of factors such as geographic location, health care settings and diagnostic practices. The most common symptoms observed in older adults with RSV infection were cough, sputum production and fever, followed by dyspnoea, sore throat and rhinorrhoea. Most of the old adults with RSV infection had underlying diseases, and RSV can cause significant morbidity and mortality in old adults. Treatment of RSV infections predominantly involve supportive care, with aerosolised ribavirin reserved for severe cases, especially immunocompromised patients. Emerging antiviral agents, including fusion and nucleoprotein inhibitors, offer promising avenues for future therapeutics. The recent approval of the bivalent RSV prefusion F protein-based vaccine for individuals aged 60 and older represents a milestone in preventive strategies. In conclusion, RSV infection remains a significant threat to older adults in the Asia-Pacific region, necessitating ongoing research and surveillance efforts. The recent vaccine approval marks a positive milestone, but further studies are crucial for refining prevention and treatment approaches.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants.

Novel intercellular spread mode of respiratory syncytial virus contributes to neutralization escape

Developing widely used respiratory syncytial virus (RSV) vaccines remains a significant challenge, despite the recent authorization of two pre-F vaccines for elderly adults. Previous reports have suggested that even when vaccine-induced immunity generates high titers of potent neutralizing antibodies targeting the pre-F protein, it may not fully inhibit breakthrough of RSV infections. This incomplete inhibition of RSV breakthrough infections can lead to an increased risk of enhanced respiratory disease (ERD) in vaccinated individuals. The reasons why potent neutralizing antibodies cannot fully prevent RSV breakthrough infections are not yet clear. In an attempt to explain this phenomenon, we investigated the effect of potent neutralizing antibodies on the intercellular spread of RSV. Our findings indicated that a specific titer of potent neutralizing antibodies, such as 5C4, could block certain modes of intercellular spread, such as the diffusion of cell-free virions and the delivery of virions through filopodia. However, these antibodies did not fully inhibit the entire process of intercellular spread. Through the use of super-resolution imaging techniques, we observed a novel and efficient spread mode called the transition of viral materials through intercellular nanotubes (TVMIN), independent of virions and insensitive to the presence of antibodies. TVMIN allowed RSV-infected cells to directly transfer viral materials to neighboring cells via intercellular nanotubes that are rich in microfilaments. TVMIN began as early as 5 h post-infection (h.p.i.) and rapidly initiated infection in recipient cells. Our data provided new insights into the intercellular spread of RSV and might help explain the occurrence of breakthrough infections.

Real-World Assessment of Economic and Clinical Outcomes in Thai Patients With Respiratory Syncytial Virus Infection Across Age Groups: A Retrospective Cohort Analysis.

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory infections worldwide, including Thailand. This study aimed to assess clinical and economic burdens of RSV infections across different age groups in Thailand. A retrospective cohort study was conducted using data from a tertiary care hospital from 2014 to 2021. Patients who tested at least one positive RSV were included and stratified into five age groups (< 2, 2-5, 5-18, 18-65, and > 65 years). Healthcare resource utilization, direct medical costs, and clinical outcomes were analyzed with descriptive statistics. Generalized linear models with gamma distributions and log link were used to model cost outcomes. Costs were reported in 2021 US dollars (USD), with 1 USD = 31.98 Thai Baht. A total of 2122 RSV-positive patients were identified, half of which (1097) were hospitalized. The median (interquartile range [IQR]) total hospitalization costs ranged from USD780 (IQR: USD488-USD1185) in those < 2 years to USD2231 (IQR: USD1250-USD4989) in those aged 65+ years. Case fatality rates among hospitalized patients also varied from 2.5% to 28.4% depending on age. Increased age, presence of comorbidities, and need for critical care were associated with higher hospitalization costs. Among RSV-positive patients, younger children experienced the greatest burden, but poorer outcomes were observed in older adults. Higher costs were associated with older age, comorbidities and critical care needs. Understanding RSV economic burdens is crucial for assessing the cost-effectiveness and public health value of vaccination programs that prioritize at-risk groups to mitigate the public health impact.