Respiratory Syncytial Virus Season Research Articles

Development and evaluation of a recombinant monoclonal human antibody with virus-neutralizing activity against the F glycoprotein of respiratory syncytial virus

Introduction. Respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections in children. RSV also poses a serious threat to the elderly and immunocompromised patients. Developing a therapy based on recombinant human antibodies to block the RSV fusion (F) glycoprotein is urgent to reduce the incidence of RSV infections and prevent associated complications. Aim. To design plasmid vectors for efficient production of the recombinant monoclonal antibody FM1 in a eukaryotic expression system targeting the RSV fusion (F) glycoprotein and to evaluate its activity against RSV subtypes A and B in vitro. Materials and methods. Constructs encoding the recombinant antibody FM1 were designed using genetic engineering. Recombinant antibodies were produced in the CHO-K1 cell line through transient expression. Antibody specimens were purified from the culture supernatant using affinity chromatography, with a modified protein A as the ligand. The virus-neutralizing activity of the antibody was evaluated in a microneutralization assay using several RSV strains on a Vero cell monolayer culture. Results. We developed a two-plasmid vector system to produce the recombinant FM1 antibody targeting the RSV F glycoprotein, using CHO cells as transient producers. The antibody was successfully produced, purified, and characterized, with its biological activity confirmed. The FM1 antibody demonstrated enhanced virus-neutralizing activity against reference and seasonal RSV strains of subtypes A and B compared to the control drug palivizumab. Conclusion. A recombinant FM1 antibody-based drug could address the import substitution challenge for protective measures against RSV infection. The authors are currently developing a stable FM1 producer clone with high productivity and viability and investigating the therapeutic efficacy of this antibody in a sublethal RSV infection mouse model.

Inpatient service utilization amongst infants diagnosed with Respiratory Syncytial Virus infection (RSV) in the United States.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among US infants. Characterizing service utilization during infant RSV hospitalizations may provide important information for prioritizing resources and interventions. The objective of this study was to describe the procedures and services received by infants hospitalized during their first RSV episode in their first RSV season, in addition to what proportion of infants died during this hospitalization. In this retrospective observational study, we analyzed three different administrative claims datasets to examine healthcare service utilization during RSV hospitalizations among infants. The study population included infants born between July 2016 and February 2020 who experienced an RSV episode during their first RSV season and had an associated inpatient hospitalization. We stratified infants into three comorbidity groups: healthy term, palivizumab-eligible, and other comorbidities. Outcomes included extracorporeal membrane oxygenation, supplemental oxygen use (in-hospital and post-discharge), mechanical ventilation (invasive and non-invasive), chest imaging, infant mortality, length of inpatient stay, intensive care unit (ICU) admission, and number of days in the ICU. Chest imaging was the most frequently administered procedure during RSV-associated hospitalizations, with approximately 34-38% of infants receiving it. Around one-quarter of infants were admitted to the ICU during their first RSV hospitalization. Median lengths of stay in the hospital were 3-4 days, extending to 4-6 days in the presence of ICU admission. Palivizumab-eligible infants had higher utilization of healthcare services and spent more time in the hospital or ICU compared to healthy infants or those with other comorbidities. This study provides insights into the utilization of healthcare services during RSV hospitalizations among infants. Understanding service utilization patterns can aid in improved management and resource allocation for infants in the United States, ultimately contributing to better outcomes and reduced healthcare costs overall. However, likely under-ascertainment of ventilation and oxygen-related services in insurance claims remains an impediment to studying these outcomes.

Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021-23).

The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined. We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020-21 (UK only; from Jan 1, 2021), 2021-22, and 2022-23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period. Among 3414 tested children, 1124 (32·9%; 95% CI 31·3-34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1-41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0-27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0-22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2-12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6-59·6]) and 261 of 724 (36·0% [32·6-39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2-1·6; the Netherlands) to 3·0 (2·8-3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4-2·9]) than in those aged 1 to <5 years (2·1 [1·9-2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6-36·0]; the UK) to 228 of 297 children (76·8% [71·5-81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9-66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7-54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1-49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5-2·2) in Spain to 4·1 days (3·3-5·0) in Belgium. RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in primary health-care systems, clinical practice, and health-care-seeking behaviour. This study emphasises the importance of considering country-specific primary care burden estimates when considering the implementation of RSV immunisations programmes. Sanofi and AstraZeneca.

Evolving Strategies for Respiratory Syncytial Virus (RSV): A Review Article of Preventive Agents and Vaccines for RSV.

The objective was to describe the pharmacology, efficacy, safety, and recommendations for the use of newly approved preventive agents and vaccines for respiratory syncytial virus (RSV) and discuss their uptake during the 2023 to 2024 RSV season. A literature search of PubMed was performed (January 2020 to February 2024) with the search terms RSV vaccine, preventive antibody, and RSV prevention. Utilization data were collected from TriNetX using the US Collaborative Network (May 2024) using the terms palivizumab, nirsevimab, and RSV prefusion F protein. Relevant English-language studies assessing the use of Food and Drug Administration (FDA)-approved preventive agents and vaccines for RSV in humans were considered. Population-level utilization data were extracted from TriNetX. Nirsevimab was observed to have noninferior efficacy and safety compared with palivizumab with less frequent administration. Nirsevimab is recommended to replace palivizumab for RSV prophylaxis in all eligible infants. Arexvy and Abrysvo are effective at reducing the risk of RSV infection in adults aged ≥60 years, and Arexvy is indicated in adults aged ≥50 years. These vaccines are equally recommended for use in the elderly adult population, but only Abrysvo is indicated and recommended for maternal administration. Most infants only require prophylaxis through either maternal RSV vaccination or nirsevimab administration. This review compares the indications for use, guideline recommendations, and clinical trial efficacy and safety data for palivizumab, nirsevimab, Abrysvo, and Arexvy to guide clinical decision-making. Novel RSV preventive agents, including Abrysvo, Arexvy, and nirsevimab, offer less burdensome dosing and administration compared with palivizumab, show promising efficacy and safety data, and expand the populations eligible for RSV prevention. Updated clinical guidance supports immediate adoption of these agents in practice, and population-level data suggest these agents were used during the 2023 to 2024 RSV season.

Use of the moving epidemic method to guide the launch of palivizumab immunization campaigns for respiratory syncytial virus in Québec, Canada.

The COVID-19 pandemic disrupted the seasonal transmission pattern of respiratory syncytial virus (RSV), challenging the launch of palivizumab immunization campaigns. This study explored the performance of the moving epidemic method (MEM) to guide the launch of such campaigns. Data were collected through a continuous RSV surveillance system (07/2013‒03/2022) in Québec, Canada. Two strategies were compared: (1) a "preestablished" approach according to which each annual campaign began on November 1 and ended upon the earliest week with an RSV positivity rate ≤ 10% after March 31; and (2) MEM, according to which each annual campaign began and ended upon meeting an epidemic threshold of RSV positivity. We estimated the proportion of RSV cases that would be covered depending on the approach used for each RSV epidemic. From seasons 2013-2014 through 2019-2020, RSV cases peaked between weeks 1and8, and all epidemic curves overlapped with an intraclass correlation coefficient (ICC) of 0.83. From 2013-2014 through 2019-2020, the epidemic periods determined by MEM and the preestablished approach covered similar proportions of RSV cases (MEM = 91.6%, preestablished = 90.7%) and had a similar duration (MEM = 21.3weeks, preestablished = 21.7weeks). With MEM, the 2021-2022 epidemic period started at week 29 and ended at week 51, covering 95.7% of cases. With the preestablished approach, the epidemic period started at week 44 and ended at week 8, covering 28.3% of cases. During normal RSV seasons, MEM is an effective alternative to the preestablished approach. However, MEM appears significantly more robust to disruptions of RSV's seasonal pattern.

Prevention of Lower Respiratory Tract Diseases caused by RSV in Infants in Poland: A Review of Current Recommendations

Introduction Respiratory syncytial virus (RSV) is the frequent cause of severe lower respiratory tract infection (LRTD) in infants, with the most severe cases concentrated among infants. Objectives The aim of this study was to review the current recommendations, as well as the availability and options for prophylaxis of LRTD caused by RSV in infants in Poland. Material and Methods Databases such as PubMed, UpToDate and Google Scholar were used for research with the keywords included: vaccine, RSV, nirsevimab, palivizumab, Abrysvo, respiratory syncytial virus, maternal immunization, prevention. The review included studies evaluating the efficacy, safety, and comparison of immunization methods against RSV, along with new recommendations and guidelines from medical societies and organizations, especially in Poland. Results In Poland, RSV prevention in infants includes: Palivizumab: Monthly injections during RSV season for high-risk infants, including preterm babies and those with serious health conditions. Nirsevimab: A single-dose monoclonal antibody recommended for all infants under 1 year, though not yet available in Poland. RSV Vaccine (RSVpreF): For pregnant women (24–36 weeks), offering passive protection to newborns. Available in Poland from May 2024. These strategies provide tailored protection based on individual needs and risks. Conclusions In Poland, effective LRTD caused by RSV prevention methods for infants are increasingly available, requiring healthcare providers and pregnant women to understand their benefits and limitations to make informed health decisions.

Practical Application of Nirsevimab Recommendations for Infants and Toddlers.

Respiratory syncytial virus (RSV) is a common respiratory tract infection that causes bronchiolitis and pneumonia in infants and children. It is the leading cause of hospitalization of infants in the United States. Nirsevimab is a long-acting monoclonal antibody recommended for the prevention of severe disease in all infants under 8 months of age and certain high-risk toddlers. Recent data demonstrate a 90% protection against hospitalization from severe RSV disease for infants who received nirsevimab in their first RSV season. Providers should understand the mechanism of action, safety, efficacy, and prescribing recommendations for nirsevimab, especially when confronted with caregivers who are hesitant about medications and vaccines. Special circumstances may require nuanced prescribing of nirsevimab to safely provide optimal protection. In these circumstances, and during drug shortages, a lens of health equity should be used to protect the highest risk populations.

New Approaches to Respiratory Syncytial Virus Prevention and Treatment.

There have been several recent advances in the prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) infection in older adults and young children. Three different vaccines are now approved for use in older adults; one of these vaccines is also approved for use in pregnant individuals for the prevention of LRTD due to RSV in their infants. In addition, a new monoclonal antibody is available to prevent RSV LRTD in infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Despite these advances in prevention efforts, specific antiviral treatment options for RSV infection remain limited. Several promising compounds remain in development.

Respiratory Syncytial Virus Disease Burden and Nirsevimab Effectiveness in Young Children From 2023-2024

During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. This study included a prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2024. Participants were children younger than 5 years with medically attended ARI. For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. Medically attended RSV-associated ARI. Overall, 28 689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19 153 during the same calendar period of 2017-2020. Of these children, 16 196 (57%) were male, and 12 444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

Notes from the Field: Rollout of Nirsevimab to Protect Infants and Young Children During the Respiratory Syncytial Virus Season - New York City, 2023-2024.

Notes from the Field: Rollout of Nirsevimab to Protect Infants and Young Children During the Respiratory Syncytial Virus Season - New York City, 2023-2024.

Lower respiratory tract infections following respiratory syncytial virus monoclonal antibody nirsevimab immunization versus placebo: Analysis from a Phase 3 randomized clinical trial (MELODY).

Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post-hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab, in healthy-term and late-preterm (i.e. gestational age ≥35 weeks) infants entering their first RSV season (MELODY). 3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants presenting with an LRTI and tested for 22 different respiratory pathogens using the BioFire® Respiratory 2.1 Panel. Incidence of RSV and non-RSV MA-LRTIs through Day 511 and LRTI severity per the ReSViNET scale were assessed. 852 nasopharyngeal swabs were collected from 561 participants through Day 511: 519 swabs from 337 nirsevimab participants and 333 swabs from 224 placebo participants. RSV and non-RSV infections were detected in 193/852 (22.7%) and 551/852 (64.7%) swabs, respectively. RSV infection rates were lower with nirsevimab compared with placebo, including RSV-rhinovirus/enterovirus coinfections. Rates of other viral infections were similar between study arms. Approximately 70% of single RSV infections and RSV coinfections were adjudicated as mild, and 26.2% of single RSV infections and 24.5% of RSV coinfections required hospitalization. Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses. ClinicalTrials.gov NCT03979313.

Respiratory syncytial virus vaccination among US adults aged ≥60 years.

Respiratory syncytial virus (RSV) vaccines have been recommended for US adults aged ≥60 years for nearly one year. However, the extent of vaccination coverage and the factors influencing uptake remain underexplored. This study aimed to evaluate national and state-specific RSV vaccination coverage among US adults aged ≥60 years and to identify demographic and socioeconomic factors that influence vaccination uptake. This cross-sectional study analyzed data from the US Census Household Pulse Survey, from January 9 to March 4, 2024, which included 49,322 adults aged ≥60 years. Participants self-reported their RSV vaccination status along with demographic and socioeconomic information. Multivariable Poisson regression was used to identify factors associated with vaccination uptake. As of March 4, 2024, RSV vaccination coverage among US adults aged ≥60 years was estimated at 22.2% (95% CI, 21.6%-22.7%). State-specific vaccination coverage ranged from 12.4% in Mississippi to 33.1% in Colorado. Coverage was higher in older age groups, with 21.2% among those aged 65-69 years, 28.1% among 70-74 years, 31.9% among 75-79 years, and 30.2% among those aged ≥80 years, compared to 10.8% among those aged 60-64 years. Racial/ethnicity disparities were evident, with lower coverage among Hispanics (18.3%) and non-Hispanic Blacks (17.6%) compared to non-Hispanic Whites (23.3%). Coverage was similar between males (22.6%) and females (21.8%). Factors positively associated with vaccination included older age, higher education level, higher household income, unemployment, and residing in the Midwest or West. Conversely, being non-Hispanic Black, uninsured, experiencing financial difficulties, and lack of COVID-19 vaccination were associated with reduced likelihood of receiving the RSV vaccine. During the first RSV season after the recommendations for RSV vaccination in US adults aged ≥60 years, uptake shows promise but is marked by significant disparities related to race/ethnicity, socioeconomic status, and geographic location. Efforts to address these disparities are crucial to enhance vaccination coverage and reduce the impact of RSV on this vulnerable population.

Estimated Vaccine Effectiveness for Respiratory Syncytial Virus–Related Lower Respiratory Tract Disease

Clinical trials have demonstrated high vaccine efficacy (VE) against lower respiratory tract disease (LRTD) but enrolled a smaller proportion of persons aged 75 years or older and those with comorbidities than seen in highest-risk populations in clinical practice settings. Additionally, VE against respiratory syncytial virus (RSV)-related hospitalizations and emergency department (ED) visits is not yet fully described. To estimate Respiratory Syncytial Virus Prefusion F (RSVpreF) effectiveness in older adults. This was a retrospective case-control study with a test negative design. Cases were adults aged 60 years or older with hospitalizations or ED visits at Kaiser Permanente of Southern California for LRTD from November 24, 2023, to April 9, 2024, who had respiratory swabs collected and tested for RSV. Two control definitions were prespecified: (1) strict controls included RSV-negative LRTD events that were negative for human metapneumovirus, SARS-CoV-2, and influenza, and positive for a nonvaccine preventable cause (primary) and (2) broad controls included all RSV-negative LRTD events (sensitivity analysis). Enhanced specimen collection was conducted to salvage clinical respiratory swabs not tested for RSV during routine care. Data were analyzed from May to September 2024. RSVpreF vaccine receipt during the first RSV season after licensure and 21 or more days before LRTD event. Estimated VE against first episode of RSV-related LRTD hospitalization or ED visit. A total of 7047 LRTD-related hospitalizations or ED encounters with RSV testing results were included. The mean (SD) age was 76.8 (9.6) years; 3819 (54.2%) were female; 839 (11.9%) were non-Hispanic Asian or Pacific Islander, 2323 (33.0%) were Hispanic, 1197 (17.0%) were non-Hispanic Black, and 2602 (36.9%) were non-Hispanic White; 998 (14.2%) were immunocompromised; and 6573 (93.3%) had 1 or more Charlson comorbidity. Using strict controls, estimated adjusted VE was 91% (95% CI, 59%-98%). Using broad controls, estimated adjusted VE was 90% (95% CI, 59%-97%). In a high-risk, general population, RSVpreF vaccination conferred protection against RSV-related LRTD in the hospital and ED settings among US adults aged 60 years or older, the majority of whom were aged 75 years or older and had comorbidities. These data support use of this vaccine in older adults.

Changes in Respiratory Syncytial Virus-Associated Hospitalisations Epidemiology After Nirsevimab Introduction in Lyon, France.

Respiratory Syncytial Virus (RSV) is a major health concern, particularly for infants. In France, Nirsevimab, a long-acting monoclonal antibody to prevent RSV-associated lower respiratory tract infections (LRTI) was available from September 2023. We described RSV-associated LRTI hospitalisations during the 2023-2024 season among infants younger than six months born at the Hospices Civils de Lyon (HCL), and evaluated the effectiveness of Nirsevimab against RSV-LRTI hospitalisation. This observational study included infants born and hospitalised at the HCL during the 2023-2024 season, along with pre-COVID-19 and 2022-2023 seasons. Information on Nirsevimab immunisation status, clinical and perinatal variables were collected through routine care. Infants' characteristics and incidence rate of hospitalisation per 100 births during 2023-2024 were compared with the historical periods overall and by delay between birth and the onset of the RSV season. Nirsevimab effectiveness was computed by the screening method. During the 2023-2024 season, 83 infants younger than six months were hospitalised with an RSV-associated LRTI. Compared with the historical periods (640 pre-COVID-19 and 123 in 2022-2023), these infants were older. Incidence rate for infants born during the period when immunisation was available were lower than the previous seasons; incidence rate ratios were 0.45 (95% confidence interval [CI]: 0.33; 0.62) in 2023-2024 compared with pre-COVID-19 period and 0.53 (95%CI: 0.36; 0.77) compared with 2022-2023 season. Nirsevimab effectiveness was 78.3% (95%CI: 55.9; 89.5) with a coverage of 79.3% in the two main HCL maternities. High Nirsevimab coverage and effectiveness were estimated in a real-world setting. A change in the age distribution of RSV-associated LRTI hospitalisations in 2023-2024 was noted compared with historical seasons.

Cost-Effectiveness of Nirsevimab for Respiratory Syncytial Virus in Infants and Young Children.

Respiratory syncytial virus (RSV) causes substantial hospitalization in US infants. The Advisory Committee on Immunization Practices recommended nirsevimab in infants younger than 8 months born during or entering their first RSV season and for children aged 8 to 19 months at increased risk of RSV hospitalization in their second season. This study's objective was to evaluate the cost-effectiveness of nirsevimab in all infants in their first RSV season and in high-risk children in their second season. We simulated healthcare utilization and deaths from RSV with and without nirsevimab among infants aged 0 to 7 months and those 8 to 19 months old over a single RSV season. Data came from published literature, US Food and Drug Administration approval documents, and epidemiologic surveillance data. We evaluated societal outcomes over a lifetime discounting at 3% and reporting in 2022 US dollars. Sensitivity and scenario analyses identified influential variables. We estimated that 107 253 outpatient visits, 38 204 emergency department visits, and 14 341 hospitalizations could be averted each year if half of the US birth cohort receives nirsevimab. This would cost $153 517 per quality-adjusted life year (QALY) saved. Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved. Nirsevimab for infants may be cost-effective, particularly among those with higher risks and costs of RSV.

Cost-Effectiveness of Maternal Vaccination to Prevent Respiratory Syncytial Virus Illness.

Respiratory syncytial virus (RSV) commonly causes hospitalization among US infants. A maternal vaccine preventing RSV in infants, RSV bivalent prefusion F maternal vaccine (RSVpreF), was approved by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices. Our objective was to evaluate the health benefits and cost-effectiveness of vaccinating pregnant persons in the United States using RSVpreF. We simulated RSV infection and disease with and without seasonal RSVpreF vaccination in half of the pregnant persons in the annual US birth cohort during weeks 32 through 36 of gestation. Model inputs came from peer-reviewed literature, Food and Drug Administration records, and epidemiological surveillance databases. The results are reported using a societal perspective in 2022 US dollars for a 1-year time frame, discounting future health outcomes and costs at 3%. Sensitivity and scenario analyses were performed. Year-round maternal vaccination with RSVpreF would prevent 45 693 outpatient visits, 15 866 ED visits, and 7571 hospitalizations among infants each year. Vaccination had a societal incremental cost of $396 280 per quality-adjusted life-year (QALY) saved. Vaccination from September through January cost $163 513 per QALY saved. The most influential inputs were QALYs lost from RSV disease, the cost of the vaccine, and RSV-associated hospitalization costs; changes in these inputs yielded outcomes ranging from cost-saving to $800 000 per QALY saved. Seasonal maternal RSV vaccination designed to prevent RSV lower respiratory tract infection in infants may be cost-effective, particularly if administered to pregnant persons immediately before or at the beginning of the RSV season.

Evaluation of Immunoglobulin A Enzyme Immunoassays to Detect Primary Respiratory Syncytial Virus Infection in Infants and Young Children.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children <2 years of age. Prior infection in a child is usually determined by RSV antibodies; however, in young children, persisting maternal immunoglobulin G antibodies can incorrectly indicate past RSV infection. We developed and evaluated 4 immunoglobulin A (IgA) antibody enzyme immunoassays (EIAs) with the RSV F, subgroup G (Ga or Gb proteins) or RSV lysate antigens to distinguish infection induced from persisting maternal RSV antibodies. We tested the EIAs against 62 cord blood specimens (group A), 39 plasma specimens from infants not exposed to an RSV season (group B), 102 plasma specimens from infants with a documented RSV infection (group C), and 124 plasma specimens from infants exposed to their first RSV season but without a documented RSV infection (group D). Among the 2 negative control groups, no group A specimens and 1 of the group B specimens were positive in all 4 IgA EIAs, giving a specificity of 100% and 97%, respectively. The sensitivity of the F, Ga, Gb, and Lysate IgA EIAs were 88%, 31%, 26%, and 61%, respectively, for group C specimens. Forty-four percent of the 124 specimens in group D were positive in the RSV-F IgA EIA. The RSV-F protein IgA EIA exhibited a high level of sensitivity and specificity for detecting previous RSV infections in the presence of maternal antibodies and can help in RSV clinical trials and epidemiologic studies in young children.

Sewage surveillance revealed the seasonality and prevalence of respiratory syncytial virus and its implications for seasonal immunization strategy in low and middle-income regions of China

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.

Hospitalization Following Outpatient Diagnosis of Respiratory Syncytial Virus in Adults

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections among adults and is estimated to cause approximately 159 000 hospitalizations among adults aged 65 years and older in the US each year. Estimates of hospitalization among adults with outpatient medically attended RSV (MA-RSV) infections are required to design interventional studies that aim to prevent hospitalization. To assess absolute risk of 28-day, all-cause hospitalization following outpatient MA-RSV infections in adults. In this cohort study, data from 3 different deidentified databases containing electronic health records (EHR) linked to closed claims data (Optum's deidentified Integrated Claims-Clinical dataset, TriNetX Linked, and Veradigm Network EHR [VNEHR] database linked with claims) were analyzed separately across 6 RSV years (October 1, 2016, to September 30, 2022) in adults with commercial or government insurance. Outpatient (eg, clinics and emergency departments) MA-RSV infections were identified based on clinical laboratory data or RSV-specific International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes. Data were analyzed from March 2023 to April 2024. The main outcome was all-cause 28-day hospitalization following outpatient MA-RSV infections among all adults and a high-risk subgroup (defined as age ≥65 years or with asthma, chronic obstructive pulmonary disease [COPD], or congestive heart failure [CHF]). In this cohort study of 67 239 MA-RSV infections in adults (2771 from Optum, 7442 from TriNetX, and 57 026 from VNEHR), most occurred among females (62%-67%) and comorbidity prevalences were 20.0% to 30.5% for COPD, 14.6% to 24.4% for CHF, 14.6% to 24.4% for asthma; 14.0% to 54.5% of individuals were aged 65 years or older. The proportion hospitalized was 6.2% (95% CI, 5.3%-7.1%) in Optum, 6.0% (95% CI, 5.4% to 6.5%) in TriNetX, and 4.5% (95% CI, 4.3%-4.6%) in VNEHR. Among the high-risk subgroup, the proportion hospitalized was 7.6% (95% CI, 6.5%-8.9%) in Optum, 8.5% (95% CI, 7.6%-9.4%) in TriNetX, and 6.5% (95% CI, 6.2%-6.8%) in VNEHR. In this cohort study of adults with outpatient MA-RSV infections from 3 large deidentified US databases across 6 RSV seasons, approximately 1 in 20 adults experienced all-cause hospitalization within 28 days. The results of this study highlight the public health need for RSV prevention and treatment.

Nirsevimab Effectiveness Against Medically Attended Respiratory Syncytial Virus Illness and Hospitalization Among Alaska Native Children - Yukon-Kuskokwim Delta Region, Alaska, October 2023-June 2024.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization. In August 2023, a preventive monoclonal antibody (nirsevimab) was recommended for all infants aged <8 months (born during or entering their first RSV season) and for children aged 8-19 months (entering their second RSV season) who have increased risk for severe RSV illness, including all AI/AN children. This evaluation in Alaska's Yukon-Kuskokwim Delta region estimated nirsevimab effectiveness among AI/AN children in their first or second RSV seasons during 2023-2024. Among 472 children with medically attended acute respiratory illness (ARI), 48% overall had received nirsevimab ≥7 days earlier (median=91 days before the ARI-related visit). For children in their first RSV season (292), nirsevimab effectiveness was 76% (95% CI = 42%-90%) against medically attended RSV illness and 89% (95% CI = 32%-98%) against RSV hospitalization. For children in their second RSV season (180), effectiveness against medically attended RSV illness was 88% (95% CI=48%-97%). Nirsevimab is effective for preventing severe RSV illness among infants entering their first RSV season and children entering their second season with increased risk for severe RSV, including all AI/AN children.