Systematic Review: Efficacy, Safety Profile, and Cost-Effectiveness of Nirsevimab Versus Palivizumab for RSV Prevention in Children Under 24 Months.

RSV prevention in infancy and asthma in later life

Respiratory syncytial virus (RSV) disease is a significant cause of morbidity and socioeconomic burden worldwide among young children. The majority of RSV-associated lower respiratory tract infections (LRTI) and mortality occurs in developing countries and is associated with various sociodemographic risk factors. Independent risk factors for severe RSV disease include age and premature birth. While RSV mortality in developed countries is lower relative to developing countries, high-risk infants with comorbidities experience higher rates of mortality. RSV LRTI is often severe and is associated with hospitalization, increased need for intensive care unit admission and mechanical ventilation, long-term complications, and caregiver stress and loss of work productivity. Overall, these factors translate to higher health care resource utilization and costs and should be factored into the consideration for RSV prophylaxis. Multiple vaccine candidates and long-acting monoclonal antibodies are in various stages of clinical development. Currently, palivizumab is the only approved RSV immunoprophylaxis available for use in specific high-risk pediatric populations. This review will discuss the socioeconomic impact and health care resource utilization of RSV-related hospitalization (RSVH) as well as various sociodemographic risk factors that can be used to identify children at high risk of developing severe RSV disease.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.

Respiratory Syncytial Virus (RSV) is one of the primary pathogen responsible for severe lower respiratory tract infections in preterm infants, placing a significant burden on patients, their families, and society. Nirsevimab, a recently developed RSV monoclonal antibody, has demonstrated promising efficacy in this population according to preliminary studies. However, there remains a need for comprehensive systematic reviews and meta-analyses to evaluate the effectiveness of nirsevimab in preventing RSV-related lower respiratory tract infections in preterm infants. A search of the PubMed and EMBASE databases was conducted to identify randomized controlled trials (RCTs) and observational studies assessing the prevention of RSV infection in preterm infants using nirsevimab. Relevant data were extracted and subjected to meta-analysis. Five studies involving a total of 7,347 preterm infants (3,987 in the nirsevimab group and 3,360 in the control group) were included. The meta-analysis revealed that nirsevimab significantly reduced the incidence of medically attended RSV-associated lower respiratory tract infections (OR = 0.25; 95% CI: 0.15, 0.40; P < 0.0001) and hospitalizations due to RSV-associated lower respiratory tract infections (OR = 0.27; 95% CI: 0.19, 0.38; P < 0.0001). Nirsevimab significantly decreases the risk of RSV-related infection in preterm infants and represents a valuable intervention for RSV prevention in this vulnerable population. https://www.crd.york.ac.uk/prospero/, identifier CRD42025629937.

What U.S. Obstetricians Need to Know About Respiratory Syncytial Virus.

Respiratory Tract Infections can be classified as upper and lower tract infections. Upper tract infections are more common such as laryngitis and pharyngitis, but the infections of lower respiratory tract are more fatal such as influenza or bronchitis. Respiratory Syncytial Virus (RSV) is one of the major causes of acute lower respiratory tract infections and consequent admissions to hospital among young children. This virus belongs to paramyxoviridae family and is an RNA virus. It can cause a range of respiratory symptoms such as cold-like symptoms to more severe respiratory distress and complications such as bronchiolitis and pneumonia. It spreads through respiratory droplets when an individual infected with it, coughs, or sneezes. Preterm infants are highly susceptible to RSV infection due to weak immune system. A new study published in 20221 unveiled the use Nirsevimab for the avoidance of RSV in late preterm and term infants. When a single dose of this monoclonal antibody was administered before the RSV season, the incidence of RSV-associated lower respiratory tract infections was 70.1% lower than the placebo group. It has an extended half-life and has high efficacy against medically attended RSV-associated lower respiratory tract infections. Moreover, the safety profile of Nirsevimab and Palivizumab, another commonly prescribed antibody medication, were similar as indicated in a study of 20222. Moreover, a study indicated that single dose of Nirsevimab was enough to provide protection during a typical season of RSV which is a bright prospect in comparison to monthly doses of palivizumab.1 Pakistan is already an endemic country for viral infections this is further compounded by the fragility of its healthcare system, rendering this issue notably significant3. The characteristics of the virus in addition to the environmental conditions that favour its transmission contribute to its typical seasonal pattern. Another research study determined that outbreaks of respiratory viruses predominantly occur during the winter and early spring seasons, with a significant proportion of confirmed cases being admitted during the months of November, December, and January.4 Another study showed that RSV circulates all around the year in Karachi, Pakistan with prime time being the monsoon rains between July and September. RSV was responsible for almost 33% acute respiratory infections related hospitalizations in young infants in this study.5 ---Continue

Background Nirsevimab for infant RSV prevention was introduced in some Northern Hemisphere countries during 2023. Chile was first to implement a universal countrywide immunization strategy following cost-effectiveness projections in the Southern Hemisphere. This strategy included all newborns born after April 1st, 2024, and infants born after October 1st, 2023. We report the first national-level impact results of this strategy up to the midwinter period. Methods Lower respiratory tract infections (LRTIs) attributed to RSV, causing intensive care (PICU) and overall hospitalizations, is being collected from integrated national databases. For effectiveness, individual hospitalization records are imputed to RSV by best matching ICD-10 codes to the national sentinel program and consolidated hospitalization records. Statistical analyses at different aggregation levels are being conducted to estimate the impact of nirsevimab. Detailed patient-level information is being collected to compare LRTI hospitalizations among those receiving or not nirsevimab using the Cox proportional hazards model. Effectiveness was estimated as (1 – hazard rate) ×100, and 95%CIs were obtained from the Cox model (NCT06511687). Results By epidemiological week 23 (mid-June 2024), nirsevimab coverage was 98% and 83% for in-season newborns and the infant catch-up group, with a total of 95,373 doses administered, from a total of 160,000 doses projected up to September 30. Effectiveness was 86% (95%CI 65-95%, 24 cases) and 75% (95%CI 64-83%, 141 cases) against PICU and overall RSV-associated hospitalizations, respectively. Among immunized and non-immunized elegible infants, days of stay were 3.95 (SD 2.46) and 7.87 (SD 6.83) (p=0.31) in the PICU and 3.23 (SD 2.02) vs 4.24 (SD 3.57) (p=0.008) in the pediatric ward, respectively. To date, no RSV deaths have been reported in Chile, compared to 13 cases in 2023. Nirsevimab associated serious adverse events have not been observed. Conclusion The nirsevimab-based nationwide immunization program is providing over 75% prevention against RSV associated PICU and overall hospitalizations in Chile, with an optimal safety profile. These results may encourage other similar countries to advance RSV prevention efforts (GRANT ANID PIA AFB230002 ISCI). Disclosures Juan P. Torres, Medical Doctor, PhD, Pfizer: Honoraria|Sanofi: Honoraria

BackgroundThe safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)–associated lower respiratory tract infection when administered in healthy infants are unclear.MethodsIn a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen.ResultsA total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P=0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P=0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P=0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group.ConclusionsNirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the standard care group (n=4019). The median age at randomisation was 4·00 months (IQR 1·0-7·0; range 0·0-12·0, and 4195 (52·1%) were male and 3862 (47·9%) were female. Up to 180 days, 12 (0·3%) of 4038 infants in the nirsevimab group and 68 (1·7%) of 4019 infants in the standard care group had been hospitalised for RSV-associated lower respiratory tract infection, corresponding to a nirsevimab efficacy of 82·7% (95% CI 67·8-91·5; p<0·0001). Most participants experienced grade 1 (2759 [68·7%] of 4016 in the nirsevimab group; 2696 [67·1%] of 4018 in the standard care group) or grade 2 (1447 [36·0%] of 4016 in the nirsevimab group; 1436 [35·7%] of 4018 in the standard care group) treatment-emergent adverse events, and no apparent safety concerns were raised up to 365 days after dosing. Nirsevimab offers consistent and sustained protection against hospitalisation due to RSV-associated lower respiratory tract infection for at least 6 months. This finding provides global health systems greater flexibility when implementing nirsevimab, providing substantial benefit in the ongoing effort to reduce the burden of infant RSV and the potential wider public health value. Sanofi and AstraZeneca.

All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study

Respiratory syncytial virus (RSV) is the leading cause of infant hospitalizations, and preterm infants and those with older siblings are at increased risk. Despite recommendations for nirsevimab prophylaxis, data on outcomes in high-risk infants are lacking. To assess the association of nirsevimab prophylaxis with RSV-related lower respiratory tract infection (LRTI) hospitalization risk and in-hospital severity among infants, overall and by high-risk groups. This retrospective multicenter cohort study comparing RSV seasons before (April 1, 2023, to March 31, 2024) and after (April 1, 2024, to March 31, 2025) universal nirsevimab prophylaxis implementation included all live births from 5 neonatal hospitals serving the Italian provinces of Ravenna, Faenza, Forlì, Cesena, and Rimini with no exclusions based on gestational age or comorbidities. Participants were followed up from hospital discharge until first RSV hospitalization, first birthday, or season end, with time-to-event analysis. Data from centralized electronic medical records included demographics, nirsevimab administration, and polymerase chain reaction-confirmed RSV. Nirsevimab prophylaxis vs no prophylaxis. The primary outcome was RSV-associated hospitalization in the first year of life. The secondary outcome was LRTI severity measures-hospital length of stay, high-flow nasal cannula (HFNC) use, and intensive care unit (ICU) admission. Hierarchical Cox proportional hazards regression models (with health care center as a random effect) were used to adjust for seasonality and relevant covariates, with sensitivity analyses using multiple models and non-RSV LRTI comparisons. Among 13 624 newborns (mean [SD] gestational age of 39.4 [1.8] weeks; 51.4% male, 4.8% preterm, and 49.5% with older siblings), nirsevimab prophylaxis achieved 79.2% coverage of the study population. Among 292 infants hospitalized with RSV LRTI (2.1%), fewer were in the postnirsevimab than prenirsevimab season group (72 [24.7%] vs 220 [75.3%]; P < .001), with a population-level reduction in hospitalization hazard (hazard ratio [HR], 0.32; 95% CI, 0.25-0.44; P < .001). In a separate within-month analysis comparing infants born in the same calendar month and therefore at similar baseline RSV risk, nirsevimab prophylaxis was associated with a lower hazard of RSV hospitalization (HR, 0.11; 95% CI, 0.06-0.21; P < .001). Prematurity (HR, 2.93; 95% CI, 2.11-4.07; P < .001) and living with older siblings (HR, 4.57; 95% CI, 4.15-5.03; P < .001) remained associated with higher hospitalization risk among infants who received prophylaxis. Among hospitalized infants, nirsevimab was associated with reduced HFNC use (OR, 0.33; 95% CI, 0.11-0.97; P = .04) but not with shorter stays (incidence rate ratio, 0.81; 95% CI, 0.63-1.03; P = .09). In this multicenter cohort study, nirsevimab prophylaxis was associated with substantially lower RSV hospitalization risk and reduced in-hospital RSV severity, supporting its implementation as a public health strategy. However, the persistent risk associated with prematurity and household RSV exposure suggests a need for supplemental approaches to optimize RSV prevention in high-risk infants.

Respiratory syncytial virus (RSV) causes a high burden of disease throughout the world, particularly in children, older people, and high-risk adults. The virus is one of the most prevalent causes of severe acute lower respiratory tract infections (LRTI), and the leading cause worldwide of infants being admitted to hospital. One study estimated that children younger than 5 years infected with RSV accounted for 33·1 million cases (uncertainty range 21·6–50·3) of acute LRTI, 3·2 million hospital admissions (2·7–3·8), and 59 600 in-hospital deaths (48 000–74 500) in 2015.

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 (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged <1 year) in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged <8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI=70%-86%) against RSV-associated ICU admission and 83% effective (95% CI=74%-90%) against acute respiratory failure when received a median of 52 days (IQR=32-89 days) and 50 days (IQR=32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants. In August 2023, the Food and Drug Administration (FDA) approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons as a single dose during 32-36 completed gestational weeks (i.e., 32 weeks and zero days' through 36 weeks and 6 days' gestation) to prevent RSV-associated lower respiratory tract disease in infants aged <6 months. Since October 2021, CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Pediatric/Maternal Work Group has reviewed RSV epidemiology and evidence regarding safety, efficacy, and potential economic impact of pediatric and maternal RSV prevention products, including RSVpreF vaccine. On September 22, 2023, ACIP and CDC recommended RSVpreF vaccine using seasonal administration (i.e., during September through end of January in most of the continental United States) for pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTI in infants aged <6 months. Either maternal RSVpreF vaccination during pregnancy or nirsevimab administration to the infant is recommended to prevent RSV-associated LRTI among infants, but both are not needed for most infants. All infants should be protected against RSV-associated LRTI through use of one of these products.