Respiratory Syncytial Virus Prevention Research Articles

Cost-effectiveness Analysis of Maternal Immunization with RSVpreF Vaccine for the Prevention of Respiratory Syncytial Virus Among Infants in Spain.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children under one year of age. In high-income countries, RSV infections cause a significant overload of care every winter, imposing a significant burden to the healthcare system, which has made the development of prevention strategies a major global health priority. In this context, a new bivalent RSV prefusion F protein-based vaccine (RSVpreF) has recently been approved. The objective of this study was to evaluate the cost-effectiveness of vaccinating pregnant women with the RSVpreF vaccine to prevent RSV in infants from the Spanish National Healthcare System (NHS) perspective. A hypothetical cohort framework and a Markov-type process were used to estimate clinical outcomes, costs, quality-adjusted life years (QALY) and cost-per-QALY gained (willingness-to-pay threshold: €25,000/QALY) for newborn infants born to RSV-vaccinated versus unvaccinated mothers over an RSV season. The base case analysis was performed from the NHS perspective including direct costs (€2023) and applying a discount of 3% to future costs and outcomes. To evaluate the robustness of the model, several scenarios, and deterministic and probabilistic analyses were carried out. All the parameters and assumptions were validated by a panel of experts. The results of the study showed that year-round maternal vaccination program with 70% coverage is a dominant option compared to no intervention, resulting in direct cost savings of €1.8 million each year, with an increase of 551 QALYs. Maternal vaccination could prevent 38% of hospital admissions, 23% of emergency room visits, 19% of primary care visits, and 34% of deaths due to RSV. All scenario analyses showed consistent results, and according to the probabilistic sensitivity analysis (PSA), the probability of maternal vaccination being cost-effective versus no intervention was 99%. From the Spanish NHS perspective, maternal vaccination with bivalent RSVpreF is a dominant alternative compared with a non-prevention strategy.

Advocacy for neonates: Will respiratory syncytial virus monoclonal antibodies and maternal vaccine be made available in India?

Respiratory syncytial virus (RSV)-related morbidity in children has been widely described. Research has led to the availability of palivizumab for decades in high-income countries. Ongoing research underlines the high priority given to this conundrum. Nirsevimab, a long-acting monoclonal antibody, and a maternal vaccine have been developed and approved for RSV. Neither of these are available in India. Improving the survival of extreme preterm neonates in our country should parallel other strategies to protect them from diseases that affect these high-risk neonates. This case series comprises sick RSV-infected infants from our centre over a single season. Of 187 young infants who presented to the Neonatology Department with features of viral lower respiratory infections, 9 (4.8%) required intensive care. All of them were positive for RSV by nasopharyngeal polymerase chain reaction. A total of 25 (13%) required hospitalisation. Preterm infants presented with apnea or severe respiratory distress. All 9 in the intensive care unit required respiratory support, and 8 needed invasive ventilation. The median duration of hospital stay for these infants was 18 (7–37) days. This report is an appeal to stakeholders towards making these evidence-based prophylactic methods available in India. A preventable problem in high-risk neonates could be reduced. Improving neonatal survival and outcomes calls for our country to be at par with high-income countries for RSV prevention. RSV-related morbidity is an endemic conundrum with a high disease burden. We could take prompt action, akin to efforts taken during the COVID-19 pandemic.

Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

Nirsevimab: Expansion of Respiratory Syncytial Virus Prevention Options in Neonates, Infants, and At-Risk Young Children.

Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

Vaccines for Respiratory Syncytial Virus Prevention in Older Adults.

This review evaluates the efficacy and safety of novel respiratory syncytial virus (RSV) vaccines approved for adults aged 60 years and older. A literature search through February 27, 2024 was conducted using search terms, such as RSV, viral respiratory illness, vaccine, RSVpreF, RSVpreF3, Prefusion F, Abrysvo, and Arexvy. Data from primary literature and vaccine prescribing information were reviewed, encompassing evaluations of clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. The literature review process resulted in 10 articles included within this article's scope, including the results of 2 major phase III trials presented in detail. Two RSV vaccines, Respiratory Syncytial Virus Vaccine (recombinant [adjuvanted]; RSVpreF3-ASO1E, Arexvy) and Respiratory Syncytial Virus Vaccine (recombinant; RSVpreF, Abrysvo), approved for preventing RSV-associated lower respiratory tract disease (LRTD) in adults aged 60 years or older in the United States are discussed. Results from Phase III trials have demonstrated the efficacy of 1 dose of these vaccines in preventing RSV-associated LRTD across 2 RSV seasons. The Advisory Committee on Immunization Practices currently recommends use of these vaccines under shared clinical decision-making for adults aged 60 years or older. Most common adverse effects include injection site reactions (eg, site pain, redness, and swelling). Administration requires a single intramuscular injection of 0.5 mL, reconstituted prior to administration. The RSVpreF3-ASO1E and RSVpreF vaccines effectively prevent RSV-associated LRTD in adults aged 60 years and older.

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study

Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis

Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy. We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993. A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces). Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions. Nanjing Medical University. For the Chinese translation of the abstract see Supplementary Materials section.

Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age.

Immunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana

ABSTRACT Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK’s Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro. These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro.

Public Health Impact of the Adjuvanted RSVPreF3 Vaccine for Respiratory Syncytial Virus Prevention Among Older Adults in the United States.

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). In the base-case analysis, approximately 56.7 million adults aged ≥ 60years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60years.

A comparative analysis of non-pharmaceutical interventions for preventing the respiratory syncytial virus in 30 European countries.

Respiratory syncytial virus (RSV) is a leading cause of childhood respiratory infections. Non-pharmaceutical interventions (NPIs) can help to reduce RSV transmission and our aim was to provide an overview of recommended NPIs across Europe during the 2022-2023 epidemic season. The webpages of national European public health agencies and ministries were reviewed and the information they provided on RSV prevention was compared with the December 2022 guidelines from the European Centre for Disease Prevention and Control. We examined 30 countries, leading to 21 issued recommendations for RSV prevention through institutional channels, including six that were specific for the 2022-2023 season. The top five recommendations were: hand and respiratory hygiene (95%), avoiding crowded spaces (67%), staying at home when ill (62%), cleaning household items (57%) and limiting contact with sick people (57%). They also included: face masks (33%), ventilating indoor spaces (29%), properly disposing of contaminated material (13%) and keeping siblings home from preschool if there was a newborn infant in the family (10%). There was significant heterogeneity in the NPIs recommended by different countries during RSV epidemics. Ongoing evaluation is essential to optimise the effectiveness of NPIs and adapt to changing RSV patterns.

Medical Costs of RSV-associated Hospitalizations and Emergency Department Visits in Children Aged

To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network. We used accounting and prospective surveillance data from six pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n=2,007) and ED visits (n=1,267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay (LOS) using chi-square tests of association. The median cost was $7,100 (IQR: $4,006-$13,355) per hospitalized child and $503 (IQR: $387-$930) per ED visit. Eighty percent (n=2,628) of our final sample were children aged <2 years. Fewer weeks' gestational age (GA) was associated with higher median costs in hospitalized children [p<0.001, ≥37 weeks' GA: $6,840 ($3,905-$12,450); 29-36 weeks' GA: $7,721 ($4,362-$15,274); <29 w weeks' GA: $9,131 ($4,518-$19,924)]. Full-term infants accounted for 70% of the total expenditures in our sample. Almost three quarters of the healthcare dollars spent originated in children under 12 months of age; the primary age group targeted by recommended RSV prophylactics. Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.

Nirsevimab: A Review.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in people of all ages and is the leading cause of hospitalization among infants in the United States. The year 2023 was exciting for RSV prevention. The Food and Drug Administration (FDA) approved 3 new tools for preventing severe lower respiratory tract RSV infections in infants, young children, and elderly persons. In May 2023, the FDA approved 2 vaccines, RSVpreF3 (Arexvy™, GSK) and RSVpreF (Abrysvo™, Pfizer), for adults ages 60 years or older to be given as a single-dose intramuscular injection. July 2023 brought the approval of the first long-acting monoclonal antibody nirsevimab (Beyfortus™, Sanofi and AstraZeneca) for the prevention of RSV disease in infants and young children. Then in August, the FDA approved a vaccine (Abrysvo™, Pfizer) to be given to pregnant women to protect their newborns through passive immunity. This article focuses on nirsevemab that has been recommended by the Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) to be administered for all infants <8 months of age and for children 8 to 19 months of age who are at increased risk for severe RSV disease.

Robust and sensitive amplicon-based whole-genome sequencing assay of respiratory syncytial virus subtype A and B.

In this paper, we report an improved high-throughput respiratory syncytial virus (RSV) whole-genome sequencing (WGS) assay performed directly on clinical samples, using a 4-primer-pool, short-amplicon PCR-tiling approach that is suitable for short-read sequencing platforms. The RSV WGS approach described in this study has increased sensitivity compared to previous approaches and can be applied to clinical specimens without the requirement for enrichment. The updated approach produces sequences of high quality consistently and cost-effectively, suitable for implementation to underpin national and global programs for the surveillance of RSV genomic variation. The quality of sequence produced is essential for preparedness for new interventions in monitoring antigenic escape, where a single point mutation might lead to a reduction in antibody binding effectiveness and neutralizing activity, or indeed in the monitoring of retaining susceptibility to neutralization by existing and new interventions.

Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

Personalized Infant Risk Prediction for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Requiring Intensive Care Unit Admission.

Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission. We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome. In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]). We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.

Parental awareness and attitudes towards prevention of respiratory syncytial virus in infants and young children in Australia.

To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.

Respiratory Syncytial Virus-Associated Hospitalizations Among Children

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention. We conducted prospective surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates. Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval [CI]: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 [95% CI: 22.5-25.2] per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 [95% CI: 1.76-2.11]). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio [aOR] = 1.97 [95% CI: 1.54-2.52] and aOR = 1.56 [95% CI: 1.18-2.06], respectively, compared with 24-59 months), prematurity (aOR = 1.32 [95% CI: 1.08-1.60]) and comorbid conditions (aOR = 1.35 [95% CI: 1.10-1.66]). Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.

Respiratory syncytial virus immunoprophylaxis: Novel opportunities and a call for equity.

With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low-to-middle-income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti-RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower-income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden.

Population Pharmacokinetics of Nirsevimab in Preterm and Term Infants.

Nirsevimab, a monoclonal antibody with an extended half-life, is approved for the prevention of respiratory syncytial virus (RSV) disease in all infants in Canada, the EU, Great Britain, and the USA. A population pharmacokinetics (PK) model was built to describe the PK of nirsevimab in preterm and term infants, and to evaluate the influence of covariates, including body weight and age, in infants. Nirsevimab PK was characterized by a 2-compartment model with first-order clearance (CL) and first-order absorption following intramuscular (IM) administration. The typical CL in a 5 kg infant was 3.4 mL/day. Body weight and postmenstrual age were the primary covariates on CL, with minor effects for race, second RSV season, and antidrug antibody status (deemed not clinically relevant). Congenital heart disease (CHD) and chronic lung disease (CLD) did not significantly impact nirsevimab PK. The final population PK model, based on 8987 PK observations from 2683 participants across 5 clinical trials, successfully predicted PK in an additional cohort of 967 healthy infants. Weight-banded dosing (50 mg in infants <5 kg; 100 mg in infants ≥5kg) was predicted to be appropriate for infants ≥1 kg in their first RSV season. Together, these data support weight-banded dosing of nirsevimab in all infants in their first RSV season, including in healthy infants, infants with CHD or CLD, and in infants born prematurely.