Prophylactic monoclonal antibodies against respiratory syncytial virus in early life: An in‐depth review of mechanisms of action, failure factors, and future perspectives

Background Despite increased recognition of the morbidity, mortality, and economic burden of respiratory syncytial virus (RSV) in adults, few studies have documented the status of post-discharge care after RSV hospitalization. This study assessed in-hospital and immediate post-discharge care status in older adults hospitalized with RSV in the US and compared it with other serious medical conditions (influenza, acute myocardial infarction (AMI), and stroke) that have long-standing disease prevention efforts. Methods This retrospective cohort study used data from Premier Healthcare Database between January 1, 2015, to December 31, 2019. Adults aged ≥ 65 years hospitalized due to primary diagnosis of RSV, influenza, AMI, or stroke were included. Discharge statuses were used to categorize the levels of immediate post-discharge care as shown in Figure 1. Descriptive statistics and Sankey diagrams were used to summarize the four cohorts. Results Overall, 2,559 RSV, 174,826 influenza, 208,448 AMI, and 274,102 stroke hospitalizations were identified with similar mean patient ages of 79.8, 76.8, 76.3, and 78.0 years, respectively. Almost all patients ( > 90%) had underlying comorbidities. The mean inpatient length of stay (LOS) was similar in the four cohorts (4.0, 4.4, 3.7, and 4.1 days, respectively), but the prevalence of mechanical ventilator use varied, i.e., 0.4%, 13.7%, 5.9%, and 1.4%, respectively. Intensive Care Unit (ICU) admissions during RSV hospitalizations were infrequent (3.0%) as compared to influenza (16.8%), AMI (24.5%), and stroke (20.5%). The mean ICU LOS for these four cohorts were 2.3, 2.8, 1.7, and 1.7 days in the same order. Immediately following discharge, moderate care was required for 23.9%, 22.9%, 14.1%, and 17.5% of RSV, influenza, AMI, and stroke hospitalizations, respectively. Elevated care was considerably more frequent for stroke hospitalizations (48.1%) than RSV (18.8%), influenza (21.4%), and AMI (19.3%) hospitalizations (Figure 2). Conclusion Older adults discharged from RSV hospitalizations require considerable care with needs comparable to influenza and AMI discharges. Given the substantial care requirements of RSV hospitalizations in older adults, focus on disease prevention efforts for RSV are needed. Disclosures Reiko Sato, PhD, Pfizer Inc: employee|Pfizer Inc: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer: Stocks/Bonds Kari Yacisin, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Poorva Sardana, MSc, Pfizer Inc: Contracted Research Neha Agrawal, MA, Pfizer Inc: Contracted Research Anchita Goswami, MSc, Pfizer Inc: Contracted Research Manvi Sharma, RPh, MBA, PhD, Pfizer Inc: Contracted Research

BackgroundThe burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.MethodsWe systematically reviewed studies of RSV and bronchiolitis published 2000–2021 (data years, 1979–2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools.ResultsWe identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6–11 months in 2006 to 50.1 per 1000 per year among infants aged 0–2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0–22.7 per 1000 in 1997–1999 and 1997–2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non–high-risk infants in 1997-2012.ConclusionsSubstantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.

Effects of maternal late-pregnancy and early-infancy exposures to respiratory syncytial virus circulating intensity on the risk for respiratory syncytial virus hospitalisation in the first two years of life: a comparative retrospective cohort study between Scotland and Singapore

Respiratory syncytial virus (RSV) remains one of the most important infectious causes of hospitalization in infants and children. This enveloped, RNA virus produces predictable yearly outbreaks of disease that typically peak between January and February in countries in the northern hemisphere.1 The outcome of RSV infection varies from mild upper respiratory tract infection in approximately 75% of infected infants and young children to severe life-threatening disease in a small percent of infected patients.2 In the United States, RSV lower respiratory tract infection accounts for nearly 50% of hospitalizations due to bronchiolitis and 25% of hospitalizations due to pneumonia.1 Serologic surveys suggest that by 2 years of age, more than 90% of all children have been infected by RSV.3 Whether RSV infection early in life predisposes to subsequent reactive airway disease remains an unanswered question. Reinfection is common, indicating that immunity to RSV following natural infection is less than complete.4-6RSV lower respiratory tract disease occurs primarily in infants under 2 years of age; most infants who require hospitalization are previously healthy infants less than 6 months of age. Premature infants, infants born with congenital heart disease, and those with chronic lung disease (such as bronchopulmonary dysplasia [BPD]) constitute additional high-risk groups with high rates of hospitalization due to RSV infection.7-13 A recent report describes RSV mortality rates among such hospitalized infants of 4% to 5%.14Pre-engraftment bone marrow transplant recipients, solid organ transplant recipients, and lymphopenic children receiving chemotherapy appear to suffer even higher mortality rates, although prospective data are not available.15 Morbidity in these groups is also great; the average hospital stay and intensity of care for such children may be several times that of previously healthy infants.Despite the importance of RSV as a pathogen in the pediatric age group, options for treatment and prevention of RSV disease are limited. Aerosolized ribavirin was licensed in 1986 for treatment of children hospitalized with severe RSV lower respiratory tract infection. The efficacy of ribavirin therapy remains controversial despite the growing number of carefully conducted trials.16 Factors that complicate evaluation of antiviral therapy include the self-limited nature of most viral respiratory tract illness, and variation in the natural history of RSV disease from patient to patient. These variables make it difficult to select and define distinct endpoints that can be used to evaluate differences between treatment and control groups.Active immunization to prevent severe RSV disease has not yet been successful. Persistent concern regarding vaccine safety in the young infant is the result of an unanticipated reaction to a formalin inactivated RSV vaccine used in trials conducted in the early 1960s.17-19 Recipients (less than 12 months of age) of the inactivated RSV vaccine experienced higher mortality and morbidity rates upon subsequent RSV infection than did infants who received the control vaccine. The immunologic mechanism for this reaction remains unclear although there appears to have been an aberration in both the cellular and humoral response to the vaccine. Vaccine development is also complicated by the limited ability of infants to mount an immune response to RSV glycoprotein antigens. Furthermore, the presence of maternal neutralizing antibodies may attenuate an active immune response in a vaccinated infant. Despite current efforts to develop subunit vaccines, peptide vaccines, or live attenuated RSV vaccines, it is unlikely that active immunization for infants will be available in the near future.20As an alternative to active immunization against RSV, several approaches to passive immunization in high-risk infants have been evaluated. Clinical trials were first conducted using standard intravenous immune globulin (IGIV). Two randomized controlled trials involving monthly infusions of standard IGIV to high-risk infants failed to demonstrate a reduction in hospitalization rates due to RSV.2122 This lack of efficacy was most likely due to a failure to attain adequate peak and trough RSV neutralizing antibody titers. With the development of an RSV-enriched immune globulin in the late 1980s (RSV-IGIV), it became possible to achieve sufficiently high neutralizing antibody levels in the outpatient setting with infusion of a reasonable fluid volume (15 mL/kg). The first RSV-IGIV prophylaxis trial (National Institute of Allergy and Infectious Disease [NIAID] trial) published in 1993 was conducted over three respiratory virus seasons and included 249 children with prematurity, chronic lung disease or congenital heart disease.23 Children who received 750 mg/kg/dose of RSV-IGIV had a 63% reduction in RSV hospitalizations and a 63% reduction in RSV hospital days relative to control patients receiving no RSV-IGIV. A second prophylaxis trial using RSV-IGIV (PREVENT trial), was conducted over one respiratory virus season and included 510 premature infants with and without BPD.24 This trial demonstrated a 41% reduction in RSV hospitalizations and a 53% reduction in RSV hospital days. A third multicenter RSV-IGIV prophylaxis trial involving 416 infants and children (Cardiac trial) failed to show an overall reduction in RSV disease severity in children with congenital heart disease (unpublished data). A meta-analysis of children less than 6 months of age from all three prophylaxis trials demonstrated a 47% reduction in RSV-induced hospitalization (95% confidence interval of .28–.82) (P = .006) (Table). However, caution must be observed in interpreting these data. Although there is considerable interest in the evaluation of hospitalization rates in subgroups of infants, none of the three trials were prospectively designed for subgroup analysis.Two additional clinical benefits of polyclonal immune globulin administration were observed in recipients of RSV-IGIV prophylaxis. The PREVENT trial demonstrated a 38% reduction in hospitalization due to respiratory tract infection by any respiratory virus and a 46% reduction in total hospital days due to all respiratory illnesses.24 Further, both the NIAID trial and the PREVENT trial demonstrated a reduction in the incidence of acute otitis media in high-dose RSV-IGIV recipients (750 mg/kg/dose) relative to low-dose or control patients.2425RSV-IGIV use in patients with congenital heart disease has been evaluated in two trials (the NIAID trial and the Cardiac trial) and has involved a total of 516 children. The safety of RSV-IGIV, particularly in children with cyanotic heart disease, is uncertain. There appeared to be an increased incidence in both morbidity and mortality, particularly in association with cardiac surgery in RSV-IGIV recipients with cyanotic heart disease as compared with placebo recipients. The deaths occurred at variable times, up to 3 months following an RSV-IGIV infusion. No explanation has yet been found. At the present time, use of RSV-IGIV should be avoided in children with cyanotic heart disease. Among children with left to right shunts who received RSV-IGIV there was not a statistically significant reduction in the overall incidence of RSV hospitalization relative to the control group. Therefore, based on the currently available data, RSV-IGIV does not appear to be indicated for most children with noncyanotic congenital heart disease. It may be that immunoprophylaxis will be beneficial in those infants with noncyanotic heart disease who also satisfy immunoprophylaxis criteria based on prematurity or the presence of BPD. The role of RSV-IGIV in infants with large left to right shunts with pulmonary hypertension remains uncertain.RSV-neutralizing antibodies are directed mainly against two surface glycoproteins. The G glycoprotein mediates RSV attachment to a cell that will support RSV replication by binding with cellular receptors containing sialic acid. The F glycoprotein mediates fusion of the viral lipid envelope with the plasma membrane of the cell. Although there may be considerable sequence divergence in the G glycoprotein between RSV subgroups, the important neutralizing epitopes of the F glycoprotein appear to be faithfully conserved between RSV strains and over time. There has been interest in the use of monoclonal antibodies for prophylaxis against RSV disease because of the possibility of intramuscular (rather than intravenous) administration. One immunoprophylaxis trial using a humanized immunoglobulin G (IgG) monoclonal antibody was conducted during the 1995–1996 respiratory season. In this large, multicenter, double-blind, randomized, placebo-controlled trial, monoclonal antibody or placebo was administered intramuscularly once a month to preterm infants during the respiratory virus season. The results proved disappointing (unpublished data). Although safe, this monoclonal antibody preparation did not reduce RSV hospitalization rates at the dose administered. A second multicenter prophylaxis trial using a higher dose of a somewhat different humanized murine IgG monoclonal antibody and involving over 1500 patients is currently underway.RSV transmission occurs primarily by direct introduction of virus contaminated secretions onto mucous membranes of the upper airway. Bronchiolitis and pneumonia develop when RSV from the upper airway is aspirated into the lungs. The presence of RSV immunoglobulin A (IgA) nasal antibody may protect infants against the low titer of RSV that initiates infection. Studies in experimental animals demonstrate that intranasal administration of a murine monoclonal IgA directed against the RSV F glycoprotein significantly reduced viral replication in the nasal turbinates and the lungs.2627 Phase III prophylaxis trials to evaluate topical daily instillation of IgA antibody as nose drops are currently in progress in high-risk infants.The severity of RSV infection appears to be a function of both a direct viral cytopathic effect and the immune response of the host. Evidence supporting the concept that antiviral activity alone may not be sufficient to attenuate RSV disease expression comes from the unpublished trial demonstrating little if any benefit from prophylaxis with monoclonal IgG antibody, and from the clinical trials that show little beneficial effect from RSV-IGIV in the treatment of established RSV disease in infants.28 The beneficial effect on RSV disease severity that is derived from immunoprophylaxis with a hyperimmune polyclonal product may not be due to RSV neutralizing antibody alone.29 What other critical functions might be present in RSV-IGIV that are not present in a preparation of monoclonal antibodies? Recognized immunomodulatory functions of standard IGIV include: alteration of cytokine production,30 inhibition of T-cell proliferation in vitro,31 increase in natural killer cell activity,32 increase in antibody dependent cell cytotoxicity,32 and neutralization of superantigen activity.33 How important these or other as yet unrecognized immunomodulatory functions are in the attenuation of RSV disease expression remains to be determined.The cost of immunoprophylaxis with RSV-IGIV (licensed in 1996 by the Food and Drug Administration and sold under the trade name RespiGam) over one respiratory season is approximately $5000.34Therefore, it is important that prophylaxis be reserved for carefully selected infants. A recently published consensus statement reviewed the existing literature on RSV disease in various high-risk groups and offered the following guidelines for selection of RSV-IGIV eligible patients15:It must be remembered that the majority of children hospitalized due to RSV disease are previously healthy, young infants. During the 1995–1996 respiratory virus season, 69% of 95 children hospitalized at the New England Medical Center with RSV infection were full-term infants with normal cardiac and pulmonary status. Therefore, use of RSV-IGIV in appropriately selected, high-risk infants is unlikely to dramatically reduce the overall number of RSV induced admissions. However, high-risk children have a disproportionately high economic impact on RSV-associated health care costs because of the greater disease severity and the complexity of care required for these groups. In appropriately selected infants for whom the risk of hospitalization due to RSV and other respiratory viruses is greatest, passive immunoprophylaxis should have an important medical impact and improve their quality of life.

The causal direction in the association between respiratory syncytial virus hospitalization and asthma

To compare pediatric respiratory syncytial virus (RSV) hospitalizations in the United States to regional RSV activity and inpatient palivizumab administration. We characterized inpatients, excluding newborns, with RSV from the Pediatric Health Information System (July 2010-June 2013). RSV regional activity timing was defined by the National Respiratory and Enteric Virus Surveillance System. RSV hospitalization season (defined by at least 3 SDs more than the mean regional baseline number of RSV hospitalizations for 3 consecutive weeks) was compared with RSV regional activity season (2 consecutive weeks with ≥10% RSV-positive testing). Logistic regression was used to determine predictors of hospitalization timing (ie, during or outside of regional activity season). We also assessed the timing of inpatient palivizumab administration. There were 50 157 RSV hospitalizations. Mean RSV hospitalization season onset (early November) was 3.3 (SD 2.1) weeks before regional activity season onset (early December). Hospitalization season offset (early May) was 4.4 (SD 2.4) weeks after activity season offset (mid-April). RSV hospitalization and activity seasons lasted 18 to 32 and 13 to 23 weeks, respectively. Nearly 10% of hospitalizations occurred outside of regional activity season (regional ranges: 5.6%-22.4%). Children with chronic conditions were more likely to be hospitalized after regional activity season, whereas African American children were more likely to be hospitalized before. Inpatient palivizumab dosing was typically initiated before the start of RSV hospitalizations. There is regional variation in RSV hospitalization and activity patterns. Many RSV hospitalizations occur before regional activity season; high-risk infants may require RSV immunoprophylaxis sooner.

Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze

A population-based study of the impact of palivizumab on confirmed Respiratory Syncytial Virus (RSV) hospitalizations over a 7-year period within and between two similar health regions . Clinicians in Calgary implemented palivizumab prophylaxis for high-risk infants during the last four RSV seasons; clinicians in Edmonton did not. The two cities are part of a unified health care system and similar sociodemographics. Infants <36 weeks (wk) of gestational age (GA) were identified. RSV prophylaxis data and RSV-hospitalizations for high-risk infants eligible for prophylaxis were reviewed, as well as that of moderate-risk infants (33-35 weeks GA) for whom RSV prophylaxis was not given a high priority in the recommendations published by the Canadian Paediatric Society (CPS). Prevalence of RSV hospitalization before and after palivizumab was determined (1995-1998 and 1999-2002, respectively). There were 411 high-risk infants eligible for palivizumab prior to its provision (Pre) and 496 during the prophylaxis program (Post) in Calgary. There were 401 Pre and 425 Post in Edmonton, where no such prophylaxis program was implemented. In Calgary where palivizumab was offered (Post), RSV hospitalization was significantly reduced: 7.3% Pre versus 3.0% Post (OR, 2.53, 95% CI, 1.34, 4.76). No reduction was observed in Edmonton where palivizumab was not offered: 5.0% Pre versus 7.1% Post (OR, 1.45, 95% CI, 0.81, 2.59; P = 0.212). RSV hospitalizations did not change for moderate-risk infants not receiving palivizumab in Calgary (OR, 1.26, 95% CI, 0.75, 2.12; P = 0.389). An RSV prevention program with palivizumab for high-risk infants reduced RSV hospitalizations, providing "real life" evidence of the benefits of this prophylaxis strategy. Further research is required to determine if specific sub-sets of moderate-risk infants would also benefit from an RSV prophylaxis program with palivizumab.

Estimating respiratory syncytial virus (RSV) burden in adults is challenging because of non-specific symptoms, infrequent standard-of-care testing, resolution of viral shedding before seeking medical care, test positivity that varies by specimen site in the upper airway and lower diagnostic test sensitivity compared to children. Conducting prospective observational studies to assess RSV burden in adults is time- and resource-intensive. Thus, model-based approaches can be applied using existing data to obtain more accurate estimates of RSV burden. This protocol establishes essential elements for estimating RSV incidence rate in adults using a time series model-based approach. It can be tailored to specific databases and applied globally across countries, enabling estimation of local RSV disease burden to inform public health decision-making, including immunization policy. Data are analysed using a quasi-Poisson regression model, considering the effect of baseline trends and pathogen co-circulation, stratified by age and risk status. Pathogen co-circulation is represented by viral proxies defined based on ICD code groupings indicating RSV and influenza-specific hospitalizations, lagged 0 up to 4weeks based on the model selection. A final model is constructed in two steps: optimization of the time trend (using p-values) and selection of the viral proxy lag time (using test statistics, to prioritize the most biologically plausible option). The yearly incidence rate and percentage of events attributable to RSV are estimated from the final model. Confidence intervals are calculated using residual bootstrapping. Outcomes to be modelled are based on administrative ICD code groupings and include the number of cardiorespiratory, respiratory and cardiovascular events in a specific care setting (e.g., general practitioner visit, emergency department visit, hospitalization and death). Cardiovascular events are limited to those for which existing evidence suggests an association with RSV infection. Additional secondary outcomes are constructed as a subset of the primary outcomes based on specific ICD code groups.

Respiratory viral infections (RVIs) are associated with elevated cardiovascular risk; however, less is known about cardiac complications after hospitalization for respiratory syncytial virus (RSV) vs other vaccine-preventable RVIs (COVID-19 or influenza). To compare the risk of acute cardiovascular complications in adults hospitalized for RSV vs COVID-19 or influenza. This population-based cross-sectional study, conducted before RSV vaccination rollout in Singapore, assessed all adults hospitalized for RSV or influenza (January 1, 2017, to June 30, 2024) and all adults hospitalized for COVID-19 during Omicron XBB/JN.1 transmission (January 1, 2023, to June 30, 2024). Hospitalization for RSV, influenza (vaccinated or unvaccinated), or COVID-19 (boosted [≥3 vaccine doses] or unboosted [<3 vaccine doses]). Cardiovascular events during RSV, influenza, or COVID-19 hospitalization, defined as any cardiac, cerebrovascular, or thrombotic event, occurring from admission until discharge or death. Odds of any cardiovascular event (RSV vs COVID-19 or RSV vs influenza) and severe RVI (intensive care unit admission) with or without an acute cardiovascular event were estimated using multivariate logistic regression, adjusted for sociodemographic and clinical characteristics. A total of 32 960 RVI hospitalizations (mean [SD] patient age, 66.58 [18.99] years; 17 056 [51.7%] female) were included (2148 for RSV, 14 389 for influenza, and 16 423 for COVID-19). Of the 2148 patients hospitalized for RSV, 234 (10.9%) had an acute cardiovascular event. Higher odds of any acute cardiovascular event (adjusted odds ratio [AOR], 1.31; 95% CI, 1.12-1.54) as well as other individual cardiac events were observed in RSV hospitalizations vs boosted COVID-19 (dysrhythmia: AOR, 1.52; 95% CI, 1.19-1.94; heart failure: AOR, 1.75; 95% CI, 1.30-2.35). Similarly, higher odds of any acute cardiovascular event (AOR, 1.58; 95% CI, 1.24-2.01) as well as dysrhythmias or heart failure were observed in patients hospitalized for RSV vs unboosted COVID-19. Odds of a cardiovascular event were not significantly different in RSV vs influenza, except among contemporaneous hospitalizations after the pandemic (2023-2024), where odds of heart failure (AOR, 2.09; 95% CI, 1.21-3.59) were significantly higher in RSV hospitalizations vs vaccine-breakthrough influenza hospitalizations. Occurrence of a cardiovascular event was associated with greater odds of severe RSV requiring intensive care unit admission (AOR, 2.36; 95% CI, 1.21-4.62). In this cross-sectional study, 1 in 10 patients hospitalized for RSV had a concurrent acute cardiovascular event. Odds of cardiac events were significantly higher in RSV vs COVID-19 hospitalizations in both vaccine-boosted and unboosted individuals. In contemporaneous hospitalizations for RSV or influenza after the pandemic (2023-2024), odds of heart failure were significantly higher in RSV hospitalizations vs vaccine-breakthrough influenza hospitalizations. These findings suggest that patients with preexisting cardiovascular risk should consider vaccination against RVIs.

IntroductionThe REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This second publication covers the risk and burden of RSV infection in preterm infants born at <37 weeks’ gestational age (wGA) without chronic lung disease or congenital heart disease.MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. Studies reporting data for hospital visits/admissions for RSV infection among preterm infants as well as studies reporting RSV-associated morbidity, mortality, and risk factors were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.Results2469 studies were identified of which 85 were included. Preterm infants, particularly those born at lower wGA, tended to have higher RSV hospitalization (RSVH) rates compared with otherwise healthy term infants (high SOE). RSVH rates ranged from ~5 per 1000 children to >100 per 1000 children with the highest rates shown in the lowest gestational age infants (high SOE). Independent risk factors associated with RSVH include: proximity of birth to the RSV season, living with school-age siblings, smoking of mother during pregnancy or infant exposure to environmental smoking, reduced breast feeding, male sex, and familial atopy (asthma) (high SOE). Predictive models can identify 32/33–35 wGA infants at risk of RSVH (high SOE).ConclusionRSV infection remains a major burden on Western healthcare systems and is associated with significant morbidity. Further studies focusing on the prevalence and burden of RSV in different gestational age cohorts, the changing risk of RSVH during the first year of life, and on RSV-related mortality in preterm infants are needed to determine the true burden of disease.FundingAbbVie.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0130-1) contains supplementary material, which is available to authorized users.

Morbidity and health care resource utilization subsequent to respiratory syncytial virus hospitalization among infants born at 33 to 35 completed weeks gestation

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalisations in infants (age < 1 year) and young children. Little is known on RSV epidemiology and related inpatient healthcare resource use (HCRU) in Switzerland.AimTo explore RSV-related hospitalisations, inpatient HCRU and medical costs in all age groups, and risk factors for infant hospitalisations in Switzerland.MethodsWe used national hospital registry data from 2003 to 2021 identifying RSV cases with ICD-10-GM codes, and described demographic characteristics, HCRU and associated medical costs of RSV inpatients. The effect of risk factors on infant hospitalisation was estimated with logistic regression.ResultsWe observed a general increase and biannual pattern in RSV hospitalisations between 2003/04 and 2018/19, with 3,575 hospitalisations in 2018/19 and 2,487 in 2019/20 before numbers declined in 2020/21 (n = 902). Around two thirds of all hospitalisations occurred in infants. Mean (median) age was 118 (85) days in hospitalised infants and 74 (77) years in hospitalised adult patients (> 18 years); 7.2% of cases required intensive care unit stay. Mean inpatient medical costs were estimated at EUR 8,046. Most (90.8%) hospitalised infants with RSV were born after 35 weeks of gestation without bronchopulmonary dysplasia or congenital heart disease. Low birth weight, gestational age and congenital disorders were associated with a higher risk for hospitalisation.ConclusionsRSV leads to a substantial number of hospitalisations and peaks in hospital capacity utilisation. Measures to protect all infants from an RSV hospitalisation are essential in addressing this public health challenge.

Background: Children with hemodynamically significant heart disease (HS-HD) are at risk for morbidities and mortality due to respiratory syncytial virus (RSV). Palivizumab was approved for RSV prophylaxis in 1998. Guidelines released in December 2003 recommend palivizumab for all children &lt; 2 yrs with HS-HD. We sought to define the impact of RSV prophylaxis in children with HS-HD by evaluating trends in U.S. RSV hospitalizations. Methods: The 1997, ’00, ’03, ’06 and ’09 Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) were used to estimate U.S. RSV hospitalizations in children &lt; 2 yrs, overall and in those with HS-HD, using standard HCUP weighting methods. RSV was defined by ICD-9-CM codes for RSV infection. HS-HD was defined using ICD-9-CM codes from the Clinical Classifications Software for congestive heart failure, or an ICD-9-CM code for pulmonary hypertension, common truncus, common ventricle, or hypoplastic left heart syndrome. Results: Our cohort included an estimated 461,491 RSV hospitalizations; 2,132 in children with HS-HD. Figure 1 depicts hospitalizations over time. There was no evident trend in number of overall RSV hospitalizations, however RSV hospitalizations in children with HS-HD declined by 39% from ’97 to ‘09. The largest decline was from ’97-’03. RSV hospitalizations in children with HS-HD relative to overall hospitalizations in children with HS-HD declined annually from ’97-’06 with a small increase in ‘09 (3.8%, 3.5%, 3.0%, 2.3% and 2.6% for successive analytic years). In 2009 mean hospital length of stay for children with HS-HD and RSV was 22.5 ± 2.1 days. Conclusions: RSV disease burden in children with HS-HD has declined since palivizumab approval. Much of this decline occurred before palivizumab was recommended for use in HS-HD, perhaps reflecting early adoption of prophylaxis, or greater awareness of alternative preventative strategies. RSV remains a significant cause of morbidity in children with HS-HD.

In 2023, new immunization strategies became available for preventing respiratory syncytial virus (RSV) hospitalizations in infants and older adults. Modeling studies to understand the population-level impact of their use are important for public health planning. To estimate the number of hospitalizations averted in 2023 to 2024 due to new RSV immunization strategies and provide scenario projections for future seasons. This decision analytical model examined RSV hospitalizations in King County, Washington, from October 7, 2023, through April 26, 2025. The population of King County was disaggregated into infants younger than 6 months, infants aged 6 to 11 months, children aged 1 to 4 years, children/adults aged 5 to 59 years, adults aged 60 to 74 years, and adults aged 75 years or older. Respiratory syncytial virus vaccination for adults aged 60 years or older, maternal RSV vaccination, and long-acting monoclonal antibodies (nirsevimab) for infants younger than 8 months. The proportion of RSV hospitalizations averted in adults aged 60 years or older and infants younger than 1 year were estimated using an RSV transmission model calibrated to RSV hospitalizations. The RSV transmission model simulated the population of King County, which includes approximately 2.3 million individuals, with 23 700 infants younger than 1 year and 446 500 adults aged 60 years or older. During the 2023 to 2024 RSV season, 21.2% of adults aged 60 to 74 years, 32.7% of adults aged 75 years or older, and 33.0% of infants were protected through active or passive immunization. A total of 125 (95% projection interval [PI], 77-192) RSV hospitalizations were averted, with most of the benefit observed in infants younger than 6 months (28.6% [95% PI, 26.9%-30.5%] reduction from baseline) and adults aged 75 years or older (14.8% [95% PI, 14.3%-15.5%] reduction from baseline). For the 2024 to 2025 season, optimistic scenarios of high immunization coverage (50% in older adults and 80% in infants) projected reductions of 29.8% (95% PI, 29.1%-30.8%) in adults aged 75 years or older and 68.8% (95% PI, 66.0%-71.7%) in infants younger than 6 months compared with a counterfactual scenario with no immunizations. Targeting infants eligible for catch-up doses of nirsevimab early in the season increased the proportion of RSV hospitalizations averted in infants aged 6 to 11 months from 31.7% (95% PI, 29.4%-33.9%) to 40.4% (95% PI, 39.0%-42.1%). If vaccine protection in adults aged 75 years or older waned by 50% in the second year after immunization, the proportion of RSV hospitalizations averted was projected to decrease to 22.2% (95% PI, 21.7%-23.0%). In this decision analytical model of RSV immunizations, the results suggest a modest reduction in RSV-diagnosed hospitalizations during the 2023 to 2024 season due to limited availability of immunization products, particularly for infants. A higher uptake earlier in the season may lead to substantial reductions in RSV hospitalizations in the 2024 to 2025 season.