Beyond Efficacy: Policy, Delivery, and Equity Determinants of Long-Acting Monoclonal Antibody Uptake for Infant RSV Prevention—A WAidid Consensus Document

1. Introduction

Despite broad regulatory approval of nirsevimab, and the more recent approval of clesrovimab, as long-acting monoclonal antibodies for the prevention of respiratory syncytial virus (RSV) disease in infants [1,2,3], real-world implementation experience remains largely centered on nirsevimab. Its uptake has varied substantially across countries, regions, healthcare systems, and population subgroups, while coverage data for clesrovimab are still limited. The heterogeneity in uptake data of nirsevimab reflects differences in national implementation strategies, reimbursement models, delivery pathways, and access to care. A key determinant of this variability is the concurrent availability of maternal RSV immunization, which alters the population eligible for infant nirsevimab administration and may lead to partial substitution between preventive approaches, since most infants are expected to receive only one of the two interventions [4].

Importantly, implementation success should not be measured exclusively by crude coverage estimates. Timeliness of administration, reach among vulnerable populations, equity across socioeconomic groups, completeness of catch-up strategies, and the reduction of missed opportunities are equally important dimensions of successful implementation. Programs achieving similar overall coverage may therefore generate substantially different public health benefits depending on the quality and equity of delivery. Implementation fidelity, defined as the degree to which preventive interventions are delivered according to their intended design, has emerged as a major determinant of successful RSV prevention programs. High nominal coverage may coexist with suboptimal population protection when administration occurs late, when eligible infants are missed, or when important socioeconomic subgroups remain underrepresented.

Recent reviews and meta-analyses have shown that nirsevimab uptake is uneven even in settings where it is prioritized for infant RSV prevention, with coverage strongly shaped by national immunization policies, financing and reimbursement mechanisms, and whether programs are universal, publicly funded, or fragmented across regional, risk-based, private, or insurance-dependent pathways [5,6,7,8]. This review goes beyond the existing literature by integrating published evidence on these determinants with real-world implementation experience, emphasizing how policy design, funding structures, and delivery models interact to influence not only overall uptake but also timeliness, consistency, and equity of access.

The organization of delivery pathways is another major determinant of implementation success. Hospital-based administration at birth, particularly before discharge from maternity units, is generally associated with higher uptake than outpatient or multi-provider models, which require additional appointments, coordination, and availability of the product in the outpatient settings. Socioeconomic inequalities, geographic barriers, and disparities in access to healthcare further contribute to both between-country and within-country variability. In addition, differences in healthcare provider awareness, clinical practice patterns, communication with caregivers, and surveillance infrastructure may substantially influence program implementation and measured coverage across health systems.

Although the clinical efficacy and real-world effectiveness of nirsevimab have now been consistently demonstrated across randomized trials and multiple national implementation programs, substantial differences remain in the population-level impact achieved by different countries. These differences are no longer primarily explained by biological efficacy but rather by variation in implementation strategies, health-system organization, financing mechanisms, delivery pathways, and equitable access. Consequently, implementation has emerged as the principal determinant of the public health value of RSV passive immunization.

Understanding the drivers of disparities in nirsevimab uptake is essential to maximize the public health impact of this preventive intervention and to ensure equitable protection against RSV disease. Uneven coverage may limit reductions in RSV-related disease burden and hospitalizations, particularly among infants and communities already at increased risk of poor health outcomes. A structured characterization of these determinants can support targeted, context-specific interventions, guide resource allocation, and help translate the high efficacy demonstrated in clinical trials into real-world effectiveness. Accordingly, this World Association for Infectious Diseases and Immunological Disorders (WAidid) consensus document moves beyond describing international uptake estimates and aims to develop a comprehensive implementation framework for infant RSV prevention. We examine how policy decisions, healthcare delivery models, organizational capacity, provider behaviour, family-level determinants, and structural inequities interact to shape real-world uptake, timeliness, and ultimately the population impact of long-acting monoclonal antibodies. Finally, we identify knowledge gaps and propose priorities for future implementation research.

2. Methods

A structured literature search was conducted in PubMed and Embase to identify relevant publications on nirsevimab and monoclonal antibody–based strategies for prevention of respiratory syncytial virus (RSV) disease in infants. The search covered studies published between January 1, 2000, and March 31, 2026. Only English-language publications were considered. The search strategy combined free-text terms and controlled vocabulary, including Medical Subject Headings (MeSH) where applicable, related to RSV, nirsevimab, monoclonal antibodies, infant immunization, implementation, uptake, coverage, effectiveness, reimbursement, access, and health equity. The following search concepts were combined using Boolean operators: (“respiratory syncytial virus” OR RSV) AND (nirsevimab OR “long-acting monoclonal antibody” OR “monoclonal antibody”) AND (infant OR newborn OR neonate) AND (uptake OR coverage OR implementation OR effectiveness OR access OR equity OR reimbursement OR policy). The electronic database search was complemented by a manual review of English-language surveillance reports, policy documents, and public health guidance from the European Centre for Disease Prevention and Control (ECDC), the UK Health Security Agency (UKHSA), and the Centers for Disease Control and Prevention (CDC), as well as by screening the reference lists of selected publications.

Eligible publications included phase II and III clinical trials, randomized controlled trials, observational studies, multicenter studies, real-world effectiveness studies, systematic reviews, meta-analyses, practice guidelines, policy statements, and relevant narrative reviews. Studies were eligible if they reported data or guidance relevant to nirsevimab use, uptake, implementation, effectiveness, coverage, access, reimbursement, delivery pathways, or determinants of disparities in administration. Publications were excluded if they were not written in English, did not address RSV prevention in infants, focused exclusively on interventions unrelated to monoclonal antibody prophylaxis or maternal RSV immunization, lacked relevance to uptake or implementation, or provided no original data, policy guidance, or substantive synthesis relevant to the review objectives. Clesrovimab was not included as a focus of this review because it was introduced only recently, and published real-world data on its uptake, implementation, coverage, and equity impact remain limited; therefore, the analysis was centered on nirsevimab, for which post-licensure implementation evidence is available.

A total of 50 sources were included in the qualitative synthesis, comprising clinical studies, real-world effectiveness studies, systematic reviews, meta-analyses, economic evaluations, policy statements, surveillance reports, and public health guidance documents relevant to nirsevimab implementation and uptake. Data were extracted and synthesized qualitatively, with emphasis on clinically and public health–relevant findings, consistency across studies, real-world implementation experience, and implications for equitable RSV prevention. Particular attention was given to national policy frameworks, delivery models, reimbursement mechanisms, demographic and socioeconomic determinants, and healthcare-system factors influencing uptake. Because of substantial heterogeneity in study design, populations, healthcare settings, implementation strategies, and outcome measures, a formal meta-analysis was not performed.

3. Implementation of Nirsevimab Use: The Role of National Policies

National policy is arguably the strongest upstream determinant of successful RSV prevention programs. Policy decisions define not only who should receive immunoprophylaxis but also how products are financed, procured, distributed, delivered, monitored, and ultimately accepted by healthcare providers and families. Consequently, apparently similar biological interventions may generate markedly different public health impact depending on the policy framework under which they are implemented. Policy frameworks differ across several dimensions that extend beyond the simple choice between maternal vaccination and infant monoclonal antibodies. These include target population definition, reimbursement mechanisms, procurement models, delivery platforms, governance structure, implementation timelines, and monitoring systems. The combination of these components constitutes the implementation architecture of RSV prevention programs and largely determines their capacity to achieve high, timely, and equitable coverage. In settings where maternal RSV immunization has been prioritized, or where decisions regarding RSV prevention have been left largely to individual providers and caregivers, nirsevimab use has generally remained limited or marginal.

In the UK, policy decisions adopted in 2023 favored the implementation of maternal RSV immunization over the universal use of long-acting monoclonal antibodies in infants. This approach was supported by considerations related to expected cost, integration within existing antenatal immunization platforms, and the potential to provide protection from birth without dependence on postnatal healthcare access [9]. In particular, the Joint Committee on Vaccination and Immunisation (JCVI) recommended the development of a national RSV prevention program prioritizing vaccination during pregnancy rather than universal neonatal administration of nirsevimab [10]. Consequently, nirsevimab was not implemented as a population-level intervention during the 2023–2024 RSV season, and its uptake in the UK remained negligible. Consistent with this, a large systematic review and meta-analysis of nirsevimab uptake, including more than 1.3 million individuals across multiple countries, did not report UK population-level uptake data, reflecting the absence of a universal infant program in this setting [11]. By contrast, uptake of maternal RSV vaccination increased progressively, exceeding 50% among pregnant women delivering in mid-2025, with coverage of 55.6% in July 2025. However, substantial regional and sociodemographic heterogeneity persisted, with coverage ranging from 64.4% in the Southeast to 47.3% in London, and from 78.5% among women of Chinese ethnicity to 30.5% among Black or Black British Caribbean women [12]. The first documented introduction of nirsevimab within the National Health Service occurred only in the 2025–2026 RSV season and was limited to a targeted, risk-based program for a restricted population of high-risk infants, including those born before 32 weeks’ gestation, estimated at approximately 7,000–9,000 infants annually [13].

In the USA, RSV prevention policy for infants has been structured as a dual-strategy model, integrating maternal immunization and nirsevimab. This approach is supported by national recommendations from the Centers for Disease Control and Prevention (CDC) [14] and the American Academy of Pediatrics (AAP) [15]. These recommendations specify that either maternal vaccination during pregnancy or nirsevimab administration to the infant should be used to prevent severe RSV disease, with most infants expected to receive only one of the two interventions rather than both. For infants born to vaccinated mothers, nirsevimab is recommended when birth occurs within 14 days of maternal immunization, a period during which transplacental antibody transfer may be incomplete. In addition, a single dose of nirsevimab is recommended for children entering their second RSV season who remain at increased risk for severe disease, thereby extending protection to selected high-risk populations beyond the first year of life.

The US experience demonstrates that combining maternal immunization with infant monoclonal antibodies substantially increases implementation complexity. Healthcare providers must evaluate maternal vaccination status, timing of vaccination, gestational age, infant age, eligibility criteria, insurance coverage, and product availability before recommending immunization. Each additional decision node increases the probability of delayed administration or missed opportunities. Initial implementation in the United States also highlighted the critical importance of supply chain resilience. Temporary shortages affected provider confidence, delayed administration, complicated inventory management, and generated regional inequities. These observations emphasize that manufacturing capacity and procurement planning represent integral components of implementation success rather than external logistical issues. During the first year of implementation in the USA, uptake remained suboptimal and highly heterogeneous, reflecting variability in program delivery, supply, financing, and access across states and healthcare systems. National surveillance during the 2023–2024 RSV season showed that only 29% of infants were protected through either maternal vaccination or nirsevimab, with approximately 18.5%–19% receiving nirsevimab directly [16,17]. Geographic variability was substantial: overall RSV prevention coverage ranged from approximately 11% in lower-performing jurisdictions to more than 50% in higher-performing states, while nirsevimab-specific uptake varied between 6.5% and 34.9% across regions [18]. Differences were also observed in the timing of administration, with only about 38% of infants receiving nirsevimab within the first week of life, partly because of early supply constraints. Temporal variation within the same RSV season further highlighted the dynamic interaction between maternal vaccination and infant monoclonal antibody use. In a large integrated healthcare system, approximately 75% of infants born at the beginning of the season (October 2023), received nirsevimab, compared with less than 30% of those born later, between January and March 2024, coinciding with increasing uptake of maternal vaccination [19]. In subsequent seasons, however, coverage improved substantially. During the 2024–2025 RSV season, approximately 47.5% of eligible infants received nirsevimab, while overall RSV immunization coverage, combining maternal vaccination and monoclonal antibody use, reached approximately 66% [20]. Early surveillance data from the 2025–2026 season suggest continued expansion of coverage, although comprehensive population-level estimates specifically for nirsevimab remain limited [21].

Across Europe, national policies have increasingly favored universal infant immunization with long-acting monoclonal antibodies. Despite differences in healthcare organization, financing mechanisms, and population size, successful European programs shared several common characteristics. These included universal publicly funded eligibility, centralized procurement, integration into neonatal care pathways, administration before hospital discharge whenever possible, and structured catch-up mechanisms for infants born outside the RSV season. During the 2025–2026 season, most countries, including Austria, Belgium, Cyprus, Czechia, Finland, France, Germany, Greece, Iceland, Ireland, Liechtenstein, Luxembourg, the Netherlands, Portugal, Spain, and Sweden, adopted universally funded and fully reimbursed infant immunization programs for RSV prevention [22]. These programs are generally delivered seasonally and target all infants below a defined age threshold, commonly younger than 6–8 months at the beginning of or during the RSV season, irrespective of underlying risk conditions. Additional provision is usually made for selected high-risk children entering their second RSV season, including those with extreme prematurity, chronic lung disease, hemodynamically significant congenital heart disease, or severe immunocompromise. In only a few countries, such as Denmark, Latvia, and Lithuania, monoclonal antibody use was restricted to infants at increased risk of severe RSV disease [22].

Several countries with funded infant programs also introduced catch-up strategies, mainly to protect infants entering their first RSV season who had been born outside the seasonal immunization campaign. These included Belgium, Cyprus, Czechia, Finland, Germany, Iceland, Ireland, Latvia, Liechtenstein, Luxembourg, the Netherlands, Spain and Portugal [22]. In contrast, funded maternal RSV vaccination programs have been implemented less consistently across Europe in the post-licensure phase. Five EU/EEA countries (Belgium, Cyprus, France, Greece, and Luxembourg), have introduced both infant monoclonal antibody programs and maternal vaccination, allowing pregnant individuals to choose between vaccination during pregnancy and postnatal administration of monoclonal antibody to their newborn. Conversely, only three countries, Romania, Poland, and Slovenia, have implemented government funded maternal RSV vaccination programs exclusively [22].

In several European countries, universal or near-universal policies have been associated with rapid achievement of high coverage. Spain represents the most comprehensive and consistently reported European experience. Universal immunization strategies introduced during the 2023–2024 RSV season achieved very high coverage, with national estimates approaching 90% of eligible infants and multicenter surveillance showing regional coverage ranging from 79% to 99% [23,24]. Population-based data from the NIRSE-GAL study in Galicia documented that 11,796 of 12,492 eligible infants received nirsevimab, corresponding to 94.4% coverage, with sustained high uptake during follow-up [25]. The Galician experience further illustrates the value of integrating implementation with digital health infrastructure. Centralized appointment systems, real-time monitoring of eligible infants, proactive recall of out-of-season births, and continuous surveillance of effectiveness and safety created a learning healthcare system capable of continuously optimizing programme performance [26]. Similar results were reported in Murcia, where 11,785 of 12,606 infants were immunized during the 2024–2025 campaign, corresponding to 93.5% overall coverage. Uptake was particularly high among infants immunized at birth, reaching 96.0%, compared with 90.5% among those receiving delayed administration [27]. Spain provides one of the clearest demonstrations that implementation strategy can be as important as biological efficacy. The combination of universal public funding, centralized procurement, maternity-based administration, high professional acceptance, and coordinated regional implementation generated consistently high coverage across multiple autonomous communities despite organizational differences. This suggests that successful implementation depends less on individual healthcare settings than on coherent system-wide organization.

Early Italian experiences illustrate the transition from initial regional implementation to more mature large-scale programs. In Valle d’Aosta, the first Italian region to implement universal nirsevimab prophylaxis during the 2023–2024 season, approximately 69%–71% of eligible neonates received nirsevimab, corresponding to 369 of 556 infants, suggesting moderate uptake during the initial rollout [28]. However, subsequent expansion to more structured regional programs yielded substantially higher coverage. In Tuscany, universal immunization with nirsevimab introduced during the 2024–2025 season achieved approximately 90%–90.5% coverage across both in-season and out-of-season birth cohorts [29].

By contrast, other European countries have reported more moderate or heterogeneous uptake. France may be considered a moderate-uptake setting, characterized by early national adoption of nirsevimab but incomplete coverage during the first implementation season. In a national ambulatory test-negative case–control study conducted during the 2023–2024 RSV season, the proportion of infants who had received nirsevimab was substantially higher among RSV-negative controls than among RSV-positive cases, 41.2% versus 13.7%, respectively. This finding highlights the coexistence of moderate population uptake with high individual-level effectiveness during the early phase of implementation [30]. In Luxembourg, national estimates suggested high neonatal coverage of approximately 84%; however, case-based analyses revealed substantial heterogeneity across maternity wards, with coverage ranging from 66% to 94% [31].

Overall, these examples indicate that national policy decisions are a major determinant of nirsevimab uptake. Universal, publicly funded programs integrated into existing maternal, neonatal, or pediatric care pathways are more likely to achieve rapid and homogeneous coverage. In contrast, risk-based strategies, fragmented delivery models, partial reimbursement, or competing preventive options without clearly defined implementation pathways may result in lower or more uneven uptake, even when nirsevimab is licensed and clinically recommended.

The experience of different countries shows that nirsevimab uptake is closely linked to the policy framework adopted for RSV prevention. Universal infant programs, dual maternal–infant strategies, risk-based approaches, and regionally implemented programs differ substantially in their operational requirements and expected coverage. The main policy models and their implications for nirsevimab uptake are summarized in Table 1.

4. External Factors Influencing Immunization Coverage

Data from countries in which maternal RSV immunization is the predominant preventive strategy, and in which monoclonal antibodies are generally reserved for infants at highest risk or for those not protected by maternal vaccination, clearly indicate that nirsevimab uptake is strongly shaped by national RSV prevention policies. However, even in countries where monoclonal antibodies represent the preferred strategy for preventing RSV disease in infants, uptake is influenced by multiple additional factors that may substantially affect overall coverage, timely administration, and equity of access. The most relevant of these determinants are discussed below.

4.1. Organizational Factors

Multiple large-scale implementation programs provide convergent evidence that the highest nirsevimab coverage is achieved when administration is embedded within routine neonatal care pathways, particularly through in-hospital delivery shortly after birth. This model has clear operational advantages over outpatient or fragmented approaches, as it reduces missed opportunities. Experience from universal birth-dose vaccination programmes, including hepatitis B and Bacillus Calmette–Guérin vaccination, has consistently shown that interventions delivered before neonatal discharge achieve higher and more equitable coverage than those relying on subsequent outpatient visits. Similar implementation principles appear applicable to RSV passive immunization. A particularly illustrative example is Chile’s national immunization program, NIRSE-CL, the first universal rollout in the southern hemisphere [32]. This program achieved coverage exceeding 94%, largely attributable to the integration of nirsevimab into routine neonatal care and the national immunization infrastructure. Importantly, administration occurred very early after birth, with a median time to immunization of approximately 1 day in the seasonal birth cohort.

Supportive evidence also comes from France, where early implementation studies conducted in maternity units showed that in-hospital administration was feasible and well accepted, with uptake exceeding 90% among eligible newborns [33]. National program data further indicate that nirsevimab was frequently administered before discharge from maternity wards, reinforcing the effectiveness of hospital-based delivery models in ensuring early protection and minimizing missed opportunities.

Hospital-based administration improves implementation through multiple independent mechanisms rather than through a single organizational advantage. First, it minimizes loss to follow-up by reaching infants before discharge. Second, it eliminates the need for caregiver-initiated healthcare seeking. Third, it reduces scheduling complexity and transportation barriers. Fourth, it standardizes eligibility assessment under neonatal care teams. Finally, it allows centralized stock management and immediate documentation within electronic medical records. These mechanisms operate synergistically to improve both coverage and timeliness.

Programs relying primarily on outpatient administration or fragmented delivery pathways tend to show lower or more variable uptake. Every additional day between birth and immunization represents a potential period of vulnerability during which infants remain susceptible to RSV infection. Consequently, implementation strategies should aim not only to maximize overall coverage but also to minimize the interval between birth and passive immunization. Immunization of infants not following discharge from the hospital requires several additional steps, including scheduling outpatient visits, ensuring parental adherence to appointments, coordinating across multiple levels of care, and maintaining consistent product availability. Each of these steps may introduce delays or missed opportunities, thereby reducing both timely protection against t RSV and overall coverage [34,35].

Nevertheless, a structured combination of in-hospital neonatal administration and organized follow-up for catch-up cohorts can maximize coverage and population benefit. A well-documented example is the NIRSE-GAL program in Galicia, Spain [25]. In this program, infants born during the RSV season were immunized in hospital on the first day of life, whereas infants born before the season were systematically identified through population registries and invited for scheduled administration in hospitals or healthcare centers. This coordinated model resulted in very high overall coverage, approximately 94.4%, and was associated with substantial reductions in RSV-related hospitalizations during the first season. Data from Tuscany in Italy also support the value of a combined strategy, showing that coordinated prophylaxis was associated with the greatest reduction in RSV-related hospitalizations [36].

Beyond national recommendations, the way nirsevimab is delivered in practice is critical to program success. Current evidence shows that timely and equitable coverage is best supported by integration into routine neonatal care, administration before hospital discharge, registry-based recall systems, and close coordination with primary pediatric services. The main organizational determinants of nirsevimab implementation are summarized in Table 2.

The effectiveness of combined delivery models depends on strong coordination across all stages of implementation. If registries are not integrated, referral pathways are unclear, communication between maternity units and primary care providers is delayed, or product distribution is unreliable, outpatient and community-based delivery may become inconsistent, leading to delays, missed opportunities, and variable coverage. France provides an example of this challenge: nirsevimab distribution was extended beyond hospitals to pharmacies, creating multiple access points. Although this approach may improve availability, community-based pathways require prescribing, dispensing, and administration, which may generate regional and provider-level variability in uptake [37].

4.2. Demographic Factors

Infant characteristics and timing of birth relative to the RSV season significantly influence access to nirsevimab. In a large USA pediatric primary care network including 7,208 eligible infants, age was a strong determinant of uptake: each additional month of age from birth was associated with a markedly lower likelihood of receiving nirsevimab (odds ratio [OR], 0.60 per month; 95% confidence interval [CI], 0.58–0.62) [38]. This finding suggests that the earliest opportunities for administration are critical and that delays after birth may rapidly translate into missed prophylaxis.

Perinatal and biological characteristics also influence uptake. Data from the French national immunization campaign, which included approximately 328,000 eligible infants, showed that prioritization of clinically vulnerable groups was reflected in real-world uptake patterns [39]. Very preterm infants (born before 32 weeks of gestation) had significantly higher odds of receiving nirsevimab than term infants (adjusted OR [aOR], 2.07; 95% CI, 1.82–2.37). Male sex was also independently associated with receipt (aOR, 1.07; 95% CI, 1.05–1.10), as was season of birth. Infants born in June–July were more likely to be immunized than those born earlier in the year, such as February–March (aOR, 1.69), reflecting the interaction between clinical prioritization, campaign timing, and proximity to the RSV season.

Race and ethnicity have also emerged as major determinants of disparity in real-world implementation. In the study by Ahmed et al. [38], black infants had significantly lower odds of receiving nirsevimab than white infants (OR, 0.53; 95% CI, 0.43–0.65), even after adjustment for age, insurance status, and neighborhood characteristics. These disparities occurred despite near-universal product availability, underscoring the role of structural and healthcare-system factors in producing inequitable access.

4.3. Economic Factors

Economic constraints remain a central barrier to the implementation of universal nirsevimab programs, although different economic components contribute unequally to limiting uptake and scalability. The most important factor is acquisition cost and overall budget impact, which directly influence whether countries can extend prophylaxis to an entire birth cohort. Economic evaluations consistently indicate that universal strategies become sustainable only below defined price thresholds. In Italy, modelling studies estimated that nirsevimab would meet commonly accepted willingness-to-pay thresholds only at a price of approximately €267–€400 per dose, with higher prices rapidly reducing cost-effectiveness and limiting feasibility at the population level [40]. Similar analyses confirm that cost-effectiveness is highly sensitive to acquisition price, assumptions regarding RSV disease burden, and baseline risk profiles, with less favorable results when prophylaxis is extended to low-risk infants [41,42]. In the USA, this constraint is particularly evident: universal immunization has been associated with an incremental cost-effectiveness ratio of approximately $153,517 per quality-adjusted life-year gained, exceeding conventional willingness-to-pay benchmarks used in many healthcare systems and thereby favoring selective or seasonal strategies over universal adoption [43]. More recent evaluations in the US similarly show that cost-effectiveness estimates are highly dependent on drug pricing, disease burden assumptions, and healthcare utilization patterns [44].

Beyond acquisition cost, health system–level delivery and reimbursement mechanisms represent major determinants of coverage and equity. The economic burden of implementation is not limited to procurement but also includes distribution, storage, inventory management, staff time, and administrative complexity, all of which may disproportionately affect less-resourced healthcare settings. Reimbursement structures are particularly important. In a USA population-based modelling study, a pharmaceutical-type reimbursement pathway, characterized by insurance-dependent coverage, prior authorization requirements, and restrictive eligibility criteria, resulted in substantially lower population coverage than a vaccine-like delivery model [45]. Transitioning to a programmatic, vaccine-like system increased coverage by 32% overall and disproportionately benefited vulnerable groups, including a 44% greater reduction in hospitalizations and emergency visits among publicly insured infants. These findings demonstrate how reimbursement and delivery frameworks can either amplify or reduce health inequities. This issue is especially relevant in private practice settings, where financial risk, delayed reimbursement, and uncertainty regarding payment may discourage providers from stocking and administering nirsevimab [46].

Socioeconomic heterogeneity in access, particularly related to insurance and income, represents a further barrier even when the product is available for a nominal price. Direct economic indicators remain strong predictors of uptake. In a large USA cohort, infants with public insurance had lower adjusted odds of receiving nirsevimab than those with private insurance (aOR, 0.80; 95% CI, 0.70–0.89) [47]. Similarly, survey-based data showed that higher household income, defined as ≥$100,000, and private insurance coverage were associated with significantly higher intention to receive nirsevimab (OR, 2.59; 95% CI, 1.07–6.22 and OR, 3.03; 95% CI, 1.27–7.23, respectively) [48]. Consistent results were reported in a large primary care network including 7,208 eligible children younger than 8 months, where only 35% of eligible infants received nirsevimab despite near-universal availability, and public insurance remained an independent negative predictor of receipt (OR, 0.79; 95% CI, 0.67–0.92) [38]. These findings reinforce the role of financial factors in shaping access.

4.4. Indirect Socioeconomic Factors

Disparities in nirsevimab uptake are not solely attributable to direct economic barriers. These also reflect indirect socioeconomic determinants, including health literacy, caregiver engagement with healthcare systems, perceived risk of infection, and community-level deprivation. These factors interact and may persist even in settings where nirsevimab is broadly available, highlighting the multifactorial nature of inequitable access.

Household exposure to healthcare environments appears to facilitate uptake [48]. Having a parent or partner employed in healthcare, which may serve as a proxy for health literacy and familiarity with preventive interventions, was among the strongest predictors of intention to receive nirsevimab. Intended uptake was reported by 74.2% of caregivers with a healthcare-affiliated household member, compared with 57.7% of those without such exposure (OR, 4.29; 95% CI, 1.75–10.5; P = 0.001). Findings from a French single-center study further support the importance of prior engagement with healthcare providers [49]. In a cohort of 1,361 infants evaluated during the first national nirsevimab immunization campaign, adherence to at least one recommended vaccine during pregnancy was independently associated with acceptance of passive immunization in newborns. Conversely, socioeconomic vulnerability was associated with lower caregiver intention to accept RSV immunoprophylaxis. In particular, participation in the Women, Infants, and Children program, used as a marker of economic and social disadvantage, was linked to a significantly lower likelihood of intending to receive nirsevimab (OR, 0.35; 95% CI, 0.13–0.91; P = 0.03). This suggests that barriers such as limited access to information, healthcare navigation challenges, and broader structural disadvantage may influence caregiver decision-making.

Behavioral and exposure-related factors further modulate the uptake of nirsevimab. In the study by Lipsett et al. [48], children attending childcare had higher odds of intended nirsevimab receipt (OR, 2.85; 95% CI, 0.94–8.65; P = 0.06) and significantly higher odds of actual uptake (OR, 3.49; 95% CI, 1.35–8.98; P = 0.01). In the same cohort, overall uptake was 66.9%, and 74.5% of caregivers expressed support for nirsevimab immunoprophylaxis for their children by reporting an intention to receive it. Childcare attendance emerged as a key behavioral driver of translation from intention to action, whereas no other factor was significantly associated with actual uptake. These findings suggest that families perceiving a higher risk of RSV exposure, or those with more structured contact with healthcare and childcare systems, may be more likely to access novel preventive interventions.

Community-level deprivation further amplifies inequities. In the study by Ahmed et al. [38], receipt of nirsevimab was independently associated with neighborhood opportunity. Infants residing in areas with a very low Child Opportunity Index, a composite measure incorporating income, educational attainment, environmental conditions, and social resources, had significantly lower odds of receiving nirsevimab than those living in high-opportunity areas (OR, 0.70; 95% CI, 0.54–0.91), even after adjustment for race, insurance status, and age. Complementary geospatial analyses using the Area Deprivation Index support this gradient. In a USA cohort of 667 infants admitted to the neonatal intensive care unit, neighborhood deprivation was associated with differences in the timing and likelihood of RSV immunoprophylaxis. Infants from lower-deprivation neighborhoods were more likely to have received prophylaxis before hospitalization, whereas those from higher-deprivation areas were more likely to receive it only after admission or to remain unprotected, suggesting delayed or reduced access among more socioeconomically disadvantaged groups [50].

Together, these findings indicate that early uptake of nirsevimab tends to cluster in more advantaged families and communities. This pattern reflects structural inequities in healthcare access, health literacy, care coordination, and preventive service delivery. Addressing these disparities requires not only adequate funding and product availability, but also integrated delivery systems, proactive outreach, reliable recall mechanisms, and targeted communication strategies for populations at greatest risk of being missed.

Taken together, the evidence indicates that suboptimal nirsevimab uptake is rarely attributable to a single barrier. Instead, it results from the interaction of policy, financing, delivery pathways, healthcare access, socioeconomic position, caregiver awareness, and surveillance capacity. These determinants, their mechanisms, and potential corrective strategies are summarized in Table 3.

5. Conclusions

The future success of infant RSV prevention will depend less on further improvements in biological efficacy than on the capacity of healthcare systems to implement existing preventive tools efficiently, equitably, and sustainably. This study has focused on the uptake of nirsevimab, since clesrovimab was introduced only recently and data on its coverage, implementation, and equity impact remain limited. Collectively, the available evidence indicates that the uptake of nirsevimab, and probably also other monoclonal antibodies for RSV prevention, is shaped by a complex interaction of policy, organizational, economic, socioeconomic, and demographic factors. Income, insurance status, geographic deprivation, caregiver health literacy, and access to healthcare all influence the likelihood that eligible infants receive prophylaxis. These determinants operate not only through individual caregiver decision-making, but also through broader structural and policy frameworks that define availability, reimbursement, delivery pathways, and equity of access. Universal recommendations, although essential, are insufficient to guarantee successful implementation. High-performing programmes consistently combine public financing, integrated neonatal delivery pathways, efficient procurement, digital monitoring systems, healthcare professional engagement, and targeted strategies addressing structural inequities.

Among these factors, the organization of neonatal and primary pediatric services appears to be particularly important for achieving high and timely coverage. In settings where universally accessible, well-structured hospital-based neonatal care is available, nirsevimab can be administered immediately after birth or before discharge, allowing infants born during the RSV season to be protected early and consistently. This approach minimizes missed opportunities and has been associated with the highest levels of coverage.

However, hospital-based administration alone is insufficient to protect the entire target population. Infants born outside the RSV season, or those not immunized before discharge, require effective outpatient delivery through primary pediatric care. This depends on coordinated communication between maternity units and community providers, reliable population registries, timely recall systems, scheduled early-life visits, and clear responsibility for administration. Where these elements are absent or poorly integrated, substantial gaps in coverage may persist, limiting the overall impact of prophylaxis on RSV-related disease burden.

An important limitation of this review is that the available evidence is derived largely from high-income countries, where regulatory access, financing mechanisms, healthcare infrastructure, birth registries, and neonatal care pathways may differ substantially from those in low- and middle-income countries. Therefore, the findings may not be fully generalizable to LMIC settings, where RSV infection has its greatest impact and where implementation may be constrained by different health-system, economic, logistical, and equity challenges. Nevertheless, many of the determinants identified in this review, including sustainable financing, clear policy recommendations, reliable product supply, integration into routine neonatal and pediatric care, caregiver awareness, and strategies to reduce socioeconomic and geographic disparities, are likely to remain relevant across settings. Their relative importance, feasibility, and impact should be specifically evaluated in LMIC contexts.

Therefore, maximizing the public health value of nirsevimab requires more than product availability or formal recommendation. Successful implementation depends on universal and sustainable financing, integration into routine neonatal and pediatric care pathways, proactive identification of eligible infants, and targeted strategies to reduce socioeconomic and geographic disparities. Strengthening these components is essential to ensure that the benefits of RSV prevention are delivered equitably and translated into meaningful reductions in RSV-related hospitalizations and morbidity across all infant populations. The next generation of RSV prevention research should therefore move beyond measuring efficacy and effectiveness towards understanding how healthcare systems can consistently translate scientific innovation into equitable population health benefit.