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Aims of the Study: Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder leading to muscle hypotonia, weakness, and respiratory and bulbar impairment. Infants with SMA have an increased risk of respiratory tract infections (RTI) including severe respiratory syncytial virus (RSV) infections. Therefore, guidelines for the treatment of SMA recommend RSV prophylaxis with palivizumab for patients aged below two years who have compromised motor functions ("non-sitters"). Since palivizumab is not approved for RSV prophylaxis in SMA patients in Switzerland, payers usually do not grant cost approvals for this indication. Therefore, this study aimed to investigate the frequency of severe RTI among SMA patients focusing on RSV infections requiring hospital treatment and to determine the long-term impact of RSV infections on the natural history of SMA., Methods: A single-centre cohort study at the tertiary paediatric Neuromuscular Centre Zurich, Switzerland, including data of SMA patients with a genetic-based therapy initiated below two years of age between May 2019 and December 2022. All hospitalisations were analysed with a focus on severe RTI and especially RSV infections, and their impact on nutritional and respiratory function. The costs of inpatient treatment of RSV infections were determined and compared with estimated expenses for RSV prophylaxis with palivizumab., Results: 12 SMA patients (median age at treatment initiation: 3.5 months, range: 0-17 months) were followed for a cumulative period of 25.75 years (7 SMA type 1; 5 SMA type 2 including one presymptomatic individual). With an incidence rate of 2.34 per patient-year, the risk of severe RTI was especially high in SMA type 1 (versus 0.1 in SMA type 2, p = 0.044). A total of 37 hospitalisations (279 hospital days) was necessary for the treatment of RTI in general; 9 of them were attributed to RSV infections (in 5 SMA type 1 patients; 84 hospital days). Only 3/12 SMA patients had received seasonal RSV prophylaxis with palivizumab. No RSV infections requiring hospital treatment occurred in patients while receiving seasonal RSV prophylaxis. During RTI, nutritional support had to be commonly initiated and continued after discharge. In 3/7 SMA type 1 patients, non-invasive ventilation was started during acute treatment for RTI and continued to the end of follow-up., Conclusion: We observed a high risk of RTI, especially RSV infections, among young SMA patients. Failure to adhere to established care protocols, for example by omitting RSV prophylaxis, may be linked to a heightened risk of morbidity in these children.

Competing Interests: MP, LG, and SM are employees of Medicines Patent Pool, which is funded by Unitaid, the Swiss Agency for Development and Cooperation, the French Ministry for Europe and Foreign Affairs, the German Agency for International Cooperation, and the Ministry of Foreign Affairs of Japan. HJZ reports grants from the Bill & Melinda Gates Foundation, the US National Institutes of Health, Pfizer, MSD, and Sanofi to their institution, outside this work; and serving on an advisory board for MSD and on the Data Safety and Monitoring Board for Moderna. NIM and JT have received support for attending meetings or travel from the ResViNET Foundation. All other authors declare no competing interests.

Competing Interests: Competing interests:: Bahaa Abu-Raya reports honoraria for participation in meetings from Sanofi, and is co-investigator on studies funded by GSK, Pfizer, Merck, Moderna, Vaccitech, and Inventprise. Joanne Langley reports funding for clinical trials from GSK, Pfizer, Merck, Moderna, Sanofi, and Sequris, paid to Dalhousie University; consulting fees from GSK, Sanofi, Enanta, and Sequris, paid to departmental academic funds; and travel support from Sanofi, Enanta, and Sequris. She reports participation on a data safety monitoring board for a pneumococcal vaccine trial with Vaxcyte and the SNAP trial. She is a medical advisor for the Nova Scotia Palivizumab for RSV Prevention Program and a member of a working group on influenza with the National Advisory Committee on Immunization. Pascal Lavoie is medical director of the British Columbia RSV Immunoprophylaxis Program and is employed by the Provincial Health Services Authority of British Columbia. He received honoraria for participating in an advisory board for Sanofi Canada. No other competing interests were declared.

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 .

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children worldwide. Using routine statutory health insurance claims data including patients from all regions of Germany, we investigated the health-care resource use and costs associated with RSV prophylaxis with palivizumab in Germany. In the database, infants from the birth cohorts 2015-2019 eligible for palivizumab immunization were identified using codes of the 10 th revision of the International Classification of Diseases (ICD-10). Health-care resource use and costs related to immunization were determined by inpatient and outpatient administrations. Over the study period, only 1.3% of infants received at least one dose of palivizumab in their first year of life. The mean number of doses per immunized infant was 4.6. From a third-party payer perspective, the mean costs of palivizumab per infant who received at least one dose in the first year of life was €5,435 in the birth cohorts 2015-2019. Despite the substantial risk of severe RSV infection, we found low rates of palivizumab utilization. Novel preventive interventions, featuring broader indications and single-dose administration per season, contribute to mitigating the burden of RSV disease across a more extensive infant population.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Background: Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present., Methods: In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated., Results: Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples., Conclusion: Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Importance: Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes., Objective: To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons., Design, Setting, and Participants: A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted., Exposures: Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood., Main Outcomes and Measures: The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported., Results: This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66)., Conclusions and Relevance: There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.

Background: Respiratory syncytial virus (RSV) is one of the most common pathogens causing severe lower respiratory tract disease in infancy and childhood. In newborns, young infants, and in infants with co-morbidities, the risk of severe infection is increased. Current protection against severe RSV infection is immunoprophylaxis with the monoclonal antibody palivizumab. The study aimed to assess the effects of palivizumab prophylaxis in the Republic of Montenegro in comparison to the pre-prophylaxis period., Methods: The study was conducted in prospective/retrospective single center format in Montenegro in the Clinical Center of Podgorica, for the period 2009-2019., Results: A total of 104 high-risk infants in the palivizumab prophylaxis program (2014-2019 RSV seasons) and 168 high-risk children without palivizumab prophylaxis (2009-2013 RSV seasons) were enrolled. A total of 51 children (49.0%) received prophylaxis for prematurity, 33 (31.7%) for bronchopulmonary dysplasia (BPD), 13 (12.5%) for hemodynamically significant heart disease/defect (HSCHD), and 7 (6.8%) for "miscellaneous" indications. In the control group most children had prematurity (101, 60.1%), followed by BPD (59, 35.1%), HSCHD (3, 1.8%), and "miscellaneous" (5, 3.4%) conditions. Readmission to the pediatric intensive care units (PICU) due to RSV infection was significantly lower in prophylaxis group (0.0 vs 16.1%, p<0.001). No lethal outcomes were observed in high-risk children with palivizumab prophylaxis compared to 2.4% in the control group., Conclusions: The introduction of RSV immunoprophylaxis as well as other new protective treatment strategies for high-risk newborns led to significant improvements in infant and childcare in Montenegro. This is the first report on palivizumab prophylaxis in Montenegro, demonstrating the effectiveness and safety of palivizumab use in clinical settings., Competing Interests: The authors declare that there is no conflict of interest.

Aim: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations., Methods: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses., Results: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results., Conclusion: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs., (© 2024. The Author(s).)

Background: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context., Methods: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described., Results: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use., Conclusions: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future., (© 2024. The Author(s).)

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable "muco-trapping" variant of motavizumab (Mota-MT), a potent neutralizing mAb against RSV F is engineered. Mota-MT traps RSV in AM via polyvalent Fc-mucin bonds, reducing the fraction of fast-moving RSV particles in both fresh pediatric and adult AM by ≈20-30-fold in a Fc-glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota-MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota-MT to RSV-infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000-fold and 100 000-fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota-MT-treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco-trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population., Methods: A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty., Results: Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective., Conclusion: Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical., Competing Interests: Conflict of interest T. Yu reported receiving personal fees from AbbVie outside the submitted work., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries' programmatic deliberations.

Synthetic cytokine receptors can modulate cellular functions based on an artificial ligand to avoid off-target and/or unspecific effects. However, ligands that can modulate receptor activity so far have not been used clinically because of unknown toxicity and immunity against the ligands. Here, we developed a fully synthetic cytokine/cytokine receptor pair based on the antigen-binding domain of the respiratory syncytial virus-approved mAb Palivizumab as a synthetic cytokine and a set of anti-idiotype nanobodies (AIP VHH ) as synthetic receptors. Importantly, Palivizumab is neither cross-reactive with human proteins nor immunogenic. For the synthetic receptors, AIP VHH were fused to the activating interleukin-6 cytokine receptor gp130 and the apoptosis-inducing receptor Fas. We found that the synthetic cytokine receptor AIP VHH gp130 was efficiently activated by dimeric Palivizumab single-chain variable fragments. In summary, we created an in vitro nonimmunogenic full-synthetic cytokine/cytokine receptor pair as a proof of concept for future in vivo therapeutic strategies utilizing nonphysiological targets during immunotherapy., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection., Methods: Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through in vitro and ex vivo serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV., Results: Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited in vitro ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ex vivo ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model., Conclusion: Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization., Competing Interests: The authors of this manuscript are current or former employees of AstraZeneca and may hold AstraZeneca stock or stock options. The authors declare that this study received funding from AstraZeneca and Sanofi. The funders had the following involvement with the study: study design; collection, analysis and interpretation of data; the writing of this article and the decision to submit it for publication., (Copyright © 2023 Brady, Cayatte, Roe, Speer, Ji, Machiesky, Zhang, Wilkins, Tuffy and Kelly.)

Introduction: Detection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness., Methods: We compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR., Results: RSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman's ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities., Discussion: Quantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mercier, Pisharody, Guy, Wan, Hegazy, D’Aoust, Kabir, Nguyen, Eid, Harvey, Rodenburg, Rutherford, Mackenzie, Willmore, Hui, Paes, Delatolla and Thampi.)

Background: Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®, RI-001, RI-002) are used with ribavirin in RSV-infected immunocompromised patients, with debated efficacy. Palivizumab-resistance (PR) can arise during treatment of persistent infections in this population. RSV-IG may confer benefit in PR-RSV infection., Methods: RSV-IG [RI-001] was provided for an immunocompromised infant with RSV-pneumonitis refractory to ribavirin and palivizumab. RSV-neutralizing antibody, respiratory RSV load (qPCR), and F-gene-sequence-detection of PR was determined. Prophylactic RSV-IG [RI-002] or palivizumab was administered in a cotton-rat model infected with wild-type and PR-RSV. Lung RSV load and neutralizing antibody were measured., Results: As protective RI-001-neutralizing antibody titers waned in the infant, a subpopulation of PR-escape mutants were detected with a fatal RSV-burden in the lungs. In PR-RSV-infected cotton rats, prophylactic RI-002 reduced RSV-load in the lungs (2.45 vs 0.28 log 10  PFU/g lung-tissue reduction, respectively, p < 0.05) and provided protective RSV-neutralizing antibody., Conclusions: RSV-IG and ribavirin use in immunocompromised patients requires further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants., Competing Interests: BP, EB, PM, ML, XCE have received research funding and/or compensation as advisor/lecturer from AstraZeneca and/or Sanofi and/or Pfizer outside the scope of this study. BRG, IK, JF, and RR employers have received payment from AstraZeneca for work on various projects. JET has nothing to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Keary et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Palivizumab has been shown to decrease RSV-related hospitalization (RSVH) risk and reduce RSVH severity. American Academy of Pediatrics (AAP) guidance on administration of palivizumab has changed over time; in 2014, palivizumab was no longer recommended in preterm infants born at 29 weeks gestational age (wGA) or later. This study's objective was to describe RSVH risk and severity in preterm infants (29-34 wGA) without comorbidities relative to healthy term infants and to each other by gestational age. Using the MarketScan Multi-State Medicaid and Commercial Databases, infants born from July 1, 2014 to June 30, 2019, at 29-34 wGA (preterm) and >37 wGA (term) were identified. During RSV seasons (November to March) from 2014 to 2020, claims incurred by infants while they were <6 months old were evaluated for RSVH and RSVH characteristics. This study included 63,351 preterm infants and 1,076,389 term infants without outpatient palivizumab administration. Rate of RSVH was higher in infants with lower wGA at birth and ranged 3.32-5.72 per 100 infant-seasons in Medicaid-insured infants and 3.21-4.84 in commercially insured infants. Relative risk of RSVH was 5-8 times higher in Medicaid-insured preterm infants and 3-5 times higher in commercially insured preterm infants compared to term infants. ICU admissions and mechanical ventilation were more common during RSVH in preterm infants relative to term infants. RSV-related outpatient healthcare utilization was also 2-3 times higher in preterm infants born at 31-34 wGA. Increased utilization of palivizumab among infants born at 29-34 wGA may decrease RSVH rates and result in less severe course in preterm infants with RSVH.

Bronchiolitis is the most common lower respiratory tract infection in young children. Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis. RSV is spread through respiratory droplets, and the number of cases varies with season. For most patients, standard precautions (e.g., hand hygiene, surface cleaning, avoiding contact with sick individuals) are recommended. However, prophylaxis with palivizumab may be considered for infants at high risk. Initial symptoms occur after an incubation period of four to six days and include rhinorrhea, congestion, sneezing, and fever. Signs of lower respiratory tract involvement may follow and include cough, tachypnea, retractions, difficulty feeding, and accessory muscle use. Diagnosis is typically clinical; routine use of radiography or viral testing is not recommended. Treatment of RSV bronchiolitis is mainly supportive. Oxygen saturation should be maintained above 90%. Hydration and nutrition should be maintained by nasogastric or intravenous routes, if needed. Therapies such as bronchodilators, epinephrine, nebulized hypertonic saline, corticosteroids, antibiotics, and chest physiotherapy are not recommended. Although most episodes of RSV bronchiolitis are self-limited, some children have an increased risk of asthma later in life.

Background: Bronchiolitis is a major cause of hospitalization in infants, particularly in the first six months of life, with approximately 60-80% of admissions due to respiratory syncytial virus (RSV) infection. Currently, no prophylactic options are available for healthy infants. The present study aimed at describing the demographic, clinical, and epidemiological characteristics of infants hospitalized for bronchiolitis in the Apulia region of Italy in 2021., Methods: From January to December 2021, data on children aged 0-12 months admitted for bronchiolitis in nine neonatal or pediatric units covering 61% of pediatric beds of hospitals in the Apulia region of Italy were analyzed. Demographic data, comorbidities, need for oxygen support, length of hospital stay, palivizumab administration, and outcomes were collected. For the purpose of the analysis, patients were divided into those aged 0-3 months and > 3 months. A multivariate logistic regression model was used to explore associations between the need for oxygen support and sex, age, comorbidities, history of prematurity, length of hospital stay, and palivizumab administration., Results: This study included 349 children aged 0-12 months admitted for bronchiolitis, with a peak of hospitalization in November (7.4 cases/1,000 children). Of these patients, 70.5% were RSV positive, 80.2% were aged 0-3 months, and 73.1% required oxygen support. Moreover, 34.9% required observation in the sub-intensive care unit, and 12.9% in the intensive care unit. Of the infants who required intensive care, 96.9% were aged 0-3 months and 78.8% were born at term. Three patients required mechanical ventilation and one, who required Extra Corporeal Membrane Oxygenation, died. Children aged 0-3 months were more likely to show dyspnea, need oxygen support, and have a longer hospital stay., Conclusions: The present study showed that almost all of the children who required intensive care support were aged ≤ 3 months and most were born at term. Therefore, this age group remains the highest risk group for severe bronchiolitis. Preventive measures such as single-dose monoclonal antibody immunoprophylaxis, and maternal and childhood vaccination against RSV, may reduce the high public health burden of bronchiolitis., (© 2023. The Author(s).)

The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to palivizumab, an anti-RSV fusion (F) protein monoclonal antibody (mAb). While anti-F protein mAbs neutralize RSV, they are unable to prevent aberrant pathogenic responses provoked by the RSV attachment (G) protein. Recently, the co-crystal structures of two high-affinity anti-G protein mAbs that bind the central conserved domain (CCD) at distinct non-overlapping epitopes were solved. mAbs 3D3 and 2D10 are broadly neutralizing and block G protein CX3C-mediated chemotaxis by binding antigenic sites γ1 and γ2, respectively, which is known to reduce RSV disease. Previous studies have established 3D3 as a potential immunoprophylactic and therapeutic; however, there has been no similar evaluation of 2D10 available. Here, we sought to determine the differences in neutralization and immunity to RSV Line19F infection which recapitulates human RSV infection in mouse models making it useful for therapeutic antibody studies. Prophylactic (24 h prior to infection) or therapeutic (72 h post-infection) treatment of mice with 3D3, 2D10, or palivizumab were compared to isotype control antibody treatment. The results show that 2D10 can neutralize RSV Line19F both prophylactically and therapeutically, and can reduce disease-causing immune responses in a prophylactic but not therapeutic context. In contrast, 3D3 was able to significantly ( p < 0.05) reduce lung virus titers and IL-13 in a prophylactic and therapeutic regimen suggesting subtle but important differences in immune responses to RSV infection with mAbs that bind distinct epitopes.

Target trial emulation (TTE) applies the principles of randomized controlled trials to the causal analysis of observational data sets. One challenge that is rarely considered in TTE is the sources of bias that may arise if the variables involved in the definition of eligibility for the trial are missing. We highlight patterns of bias that might arise when estimating the causal effect of a point exposure when restricting the target trial to individuals with complete eligibility data. Simulations consider realistic scenarios where the variables affecting eligibility modify the causal effect of the exposure and are missing at random or missing not at random. We discuss means to address these patterns of bias, namely: 1) controlling for the collider bias induced by the missing data on eligibility, and 2) imputing the missing values of the eligibility variables prior to selection into the target trial. Results are compared with the results when TTE is performed ignoring the impact of missing eligibility. A study of palivizumab, a monoclonal antibody recommended for the prevention of respiratory hospital admissions due to respiratory syncytial virus in high-risk infants, is used for illustration., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a shortacting monoclonal antibody (mAb), palivizumab (PVZ) that is expensive and intensive to administer, making it poorly suited for low-resource settings. Currently, new longer acting RSV mAbs and maternal vaccines are emerging from late-stage clinical development with promising clinical effectiveness. However, evidence of economic value and affordability must also be considered if these interventions are to be globally accessible. This systematic review's objective was to summarise existing evidence on the cost-of-illness (COI) and cost-effectiveness of RSV prevention interventions in LMICs., Methods: We conducted a systematic literature review using the Embase, MEDLINE, and Global Index Medicus databases for publications between Jan 2000 and Jan 2022. Two categories of studies in LMICs were targeted: cost-of-illness (COI) of RSV episodes and cost-effectiveness analyses (CEA) of RSV preventive interventions including maternal vaccines and long-acting mAbs. Of the 491 articles reviewed, 19 met the inclusion criteria., Results: COI estimates varied widely: for severe RSV, the cost per episode ranged from $92 to $4114. CEA results also varied-e.g. evaluations of long-acting mAbs found ICERs from $462/DALY averted to $2971/DALY averted. Study assumptions of input parameters varied substantially and their results often had wide confidence intervals., Conclusions: RSV represents a substantial disease burden; however, evidence of economic burden is limited. Knowledge gaps remain regarding the economic value of new technologies specifically in LMICs. Further research is needed to understand the economic burden of childhood RSV in LMICs and reduce uncertainty about the relative value of anticipated RSV prevention interventions. Most CEA studies evaluated palivizumab with fewer analyses of interventions in development that may be more accessible for LMICs., (© 2023. The Author(s).)

Objectives: Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy., Data Source: A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022., Data Synthesis: Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population., Conclusions: The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms., Competing Interests: Conflicts of interest Author Renato T. Stein declares that he participated in the Advisory Boards of the following companies: Abbvie, SANOFI, Pfizer and AstraZeneca, but that his participation has not influenced the writing of this article., (Copyright © 2022. Published by Elsevier Editora Ltda.)

Aim: The aim of this research is to determine the specific characteristics of the immunized children during a 15-year period and the readmissions to hospital due to potential infections of the respiratory tract., Material and Methods: This retrospective cohort study was conducted in the period from October 2008 to March 2022. The test group consists of 222 infants who met the strict criteria for immunization., Results: The study observed 222 infants who were immunized with palivizumab during the 14-year period. 124 (55.9%) infants were preterm (< 32 weeks) and 69 (31.1%) were infants with congenital heart defects, whereas 29 (13.1%) exhibited other individual risk factors. 38 (17.1%) were re-admitted to the pulmonary ward. Upon re-admission, a quick test to diagnose for RSV infections was conducted and only one infant tested positive., Results: The conclusion of our 14-year study is that palivizumab prophylaxis has truly proven itself effective for infants at risk in our region during the research time period. Over the years, the immunization season has not changed and the number of doses hasremained the same, as have the indications for immunization. What has changed, however, is an increase in the number of immunized infants without a significant increase in the number of re-admissions to hospital on account of respiratory disorders., (© 2022 Raguž et al., published by Sciendo.)

Background: Although respiratory syncytial virus (RSV) immunoprophylaxis is recommended for high-risk infants, the American Academy of Pediatrics (AAP) recommends against immunoprophylaxis in the same season following a breakthrough hospitalization due to limited risk for a second hospitalization. Evidence in support of this recommendation is limited. We estimated population-based re-infection rates from 2011-2019 in children <5 years since RSV risk remains relatively high in this age group., Materials and Methods: Using claims data from private insurance enrollees, we established cohorts of children <5 years who were followed to ascertain annual (July 1-June 30) and seasonal (November 1- February 28/29) RSV recurrence estimates. Unique RSV episodes included inpatient encounters with RSV diagnosis ≥30 days apart, and outpatient encounters ≥30 days apart from each other as well as from inpatient encounters. The risk of annual and seasonal re-infection was calculated as the proportion of children with a subsequent RSV episode in the same RSV year/season., Results: Over the 8 assessed seasons/years (N = 6,705,979) and across all age groups annual inpatient and outpatient infection rates were 0.14% and 1.29%, respectively. Among children with a first infection, annual inpatient and outpatient re-infection rates were 0.25% (95% confidence interval (CI) = 0.22-0.28) and 3.44% (95% CI = 3.33-3.56), respectively. Both infection and re-infection rates declined with age., Conclusion: While medically-attended re-infections contributed numerically only a fraction of the total RSV infections, re-infections among those with previous infection in the same season were of similar magnitude as the general infection risk, suggesting that a previous infection may not attenuate the risk for a re-infection., Competing Interests: AGW has received research funding from NIH, AHRQ, PCORI, FDA and the state of Florida and received honoraria as consultant for Arbor Pharmaceuticals and Genentech Inc, none of which is related to this work. Yoonyoung Choi is an employee at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Nduaguba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed., Objective: To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children., Data Sources: In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022., Study Selection: Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework., Main Outcomes and Measures: The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use., Results: Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest., Conclusions and Relevance: In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.

Respiratory syncytial virus (RSV) is the most common pathogen causing viral respiratory tract infections among younger children worldwide. The influence of meteorological factors on RSV seasonal activity is well-established for temperate countries; however, in subtropical countries such as Malaysia, relatively stable temperate climates do not clearly support this trend, and the available data are contradictory. Better understanding of meteorological factors and seasonality of RSV will allow effective strategic health management relating to RSV infection, particularly immunoprophylaxis of high-risk infants with palivizumab. Retrospectively, from 2017 to 2021, we examined the association between various meteorological factors (rainfall, rainy days, temperature, and relative humidity) and the incidence of RSV in children aged less than 12 years in Kuala Lumpur, Malaysia. RSV activity peaked in two periods (July to August and October to December), which was significantly correlated with the lowest rainfall ( p < 0.007) and number of rainy days ( p < 0.005). RSV prevalence was also positively associated with temperature ( p < 0.006) and inversely associated with relative humidity ( p < 0.006). Based on our findings, we recommend that immunoprophylaxis with palivizumab be administered in children aged less than 2 years where transmission of RSV is postulated to be the highest after the end of two monsoon seasons.

Background: In children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality, requiring hospital admission and intensive care. The aim of the present study was to evaluate the effect of prophylaxis with palivizumab in preventing RSV-associated hospitalization in infants with CHD., Methods: We carried out an observational, retrospective study in a paediatric cardiology division at a secondary-care centre in Italy, extracting from the database children with CHD who, from November 2004 to March 2022, matched the criteria for palivizumab prophylaxis, to evaluate the hospitalization rate in CHD patients with and without palivizumab prophylaxis and their RSV-related hospitalization characteristics compared with a group of children without CHD and no other underlying clinical conditions (control group, CG), hospitalized for RSV infection., Results: One hundred twenty-eight children with CHD were enrolled in the study, mainly (71.9%) with increased pulmonary flow, and received palivizumab prophylaxis. Twenty-seven received hospital care for bronchiolitis. Almost all CHD patients hospitalized for bronchiolitis (26 out of 27) received partial prophylaxis (≤ 3 doses). CHD patients with bronchiolitis stay longer in the hospital than control (14.4 ± 21.7 days vs 6.2 ± 2.3 days) some of which require intensive care (n = 4)., Conclusions: Our study provides evidence of the efficacy of palivizumab in protecting patients with hemodynamically significant CHD under the age of 2 years from RSV disease and its life-threatening complications. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation., (© 2023. The Author(s).)

Background and Objective: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST)., Methods: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included., Results: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231)., Conclusions: Palivizumab was highly cost-effective ( vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Evidence regarding the long-term risk of infections in preterm infants is lacking. In this study, we examined whether preterm infants developed various common childhood infections more frequently than full-term infants by the age of 2 years by analyzing data from a questionnaire completed by 67,282 mother-toddler pairs in a nationwide birth cohort study. Of the target population, 2885 (4.3%) were born prematurely. After covariate adjustment for maternal and children factors, lower respiratory tract infections appeared more frequent in preterm than in full-term infants at both 1 and 2 years (adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.05-1.41, and aOR 1.27, 95% CI 1.11-1.46, respectively). However, there was no significant difference in the frequencies of lower respiratory tract infection between preterm and full-term infants after Palivizumab administration. The risk of other common infections, such as in the upper respiratory tract infection, otitis media, urinary tract infection, gastroenteritis, herpangina, hand-foot-and-mouth disease, chickenpox, influenza virus, and adenovirus infections, was not higher in preterm than in full-term infants after covariates adjustment for maternal and children factors. These findings suggest Palivizumab prophylaxis could reduce the frequencies of lower respiratory tract infection in preterm to the same level as in full-term infants., (© 2022. The Author(s).)

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.

Respiratory syncytial virus (RSV) causes a spectrum of respiratory illnesses in infants and young children that may lead to hospitalizations and a substantial number of outpatient visits, which result in a huge economic and healthcare burden. Most hospitalizations happen in otherwise healthy infants, highlighting the need to protect all infants against RSV. Moreover, there is evidence on the association between early-life RSV respiratory illness and recurrent wheezing/asthma-like symptoms As such, RSV is considered a global health priority. However, despite this, the only prevention strategy currently available is palivizumab, a monoclonal antibody (mAb) indicated in a subset of preterm infants or those with comorbidities, hence leaving the majority of the infant population unprotected against this virus. Therefore, development of prevention strategies against RSV for all infants entering their first RSV season constitutes a large unmet medical need. The aim of this review is to explore different immunization approaches to protect all infants against RSV. Prevention strategies include maternal immunization, immunization of infants with vaccines, immunization of infants with licensed mAbs (palivizumab), and immunization of infants with long-acting mAbs (e.g., nirsevimab, MK-1654). Of these, palivizumab use is restricted to a small population of infants and does not offer a solution for all-infant protection, whereas vaccine development in infants has encountered various challenges, including the immaturity of the infant immune system, highlighting that future pediatric vaccines will most likely be used in older infants (>6 months of age) and children. Consequently, maternal immunization and immunization of infants with long-acting mAbs represent the two feasible strategies for protection of all infants against RSV. Here, we present considerations regarding these two strategies covering key areas which include mechanism of action, "consistency" of protection, RSV variability, duration of protection, flexibility and optimal timing of immunization, benefit for the mother, programmatic implementation, and acceptance of each strategy by key stakeholders. We conclude that, based on current data, immunization of infants with long-acting mAbs might represent the most effective approach for protecting all infants entering their first RSV season., Competing Interests: SE: Speaker’s fees from GSK, Pfizer, Novartis, Sanofi Pasteur, MSD and Vifor in the past three years. BA is supported by the Michael Smith Foundation for Health Research and received payment as a scientific expert of the Sanofi group of companies. KF is a member of the Australian Technical Advisory Group on Immunisation noting that this paper represents her own personal view; received honoraria as a member of the vaccine advisory boards for Seqiris and Sanofi Pasteur in the last 5 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Esposito, Abu Raya, Baraldi, Flanagan, Martinon Torres, Tsolia and Zielen.)

Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs.

Aims: Palivizumab is a monoclonal antibody which can prevent infection with respiratory syncytial virus (RSV). Due to its high cost, it is recommended for high-risk infants only. We aimed to determine the proportion of infants eligible for palivizumab treatment in England who receive at least one dose., Methods: We used the Hospital Treatment Insights database, which contains hospital admission records linked to hospital pharmacy dispensing data for 43 out of 153 hospitals in England. Infants born between 2010 and 2016 were considered eligible for palivizumab if their medical records indicated chronic lung disease (CLD), congenital heart disease (CHD) or severe immunodeficiency (SCID), and they met additional criteria based on gestational age at birth and age at start of the RSV season (beginning of October). We calculated the proportion of infants who received at least one dose of palivizumab in their first RSV season, and modelled the odds of treatment according to multiple child characteristics using logistic regression models., Results: We identified 3712 eligible children, of whom 2479 (67%) had complete information on all risk factors. Palivizumab was prescribed to 832 of eligible children (34%). Being born at <30 weeks' gestation, aged <6 months at the start of RSV season, and having two or more of CLD, CHD or SCID were associated with higher odds of treatment., Conclusion: In England, palivizumab is not prescribed to the majority of children who are eligible to receive it. Doctors managing these infants may be unfamiliar with the eligibility criteria or constrained by other considerations, such as cost., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Respiratory syncytial virus (RSV) is the predominant cause of lower respiratory tract infections (LRTI) in infancy. Preterm infants with bronchopulmonary dysplasia (BPD) are at the highest risk of severe RSV-LRTI. This is a retrospective study that analyses a nosocomial outbreak of RSV infections in the Neonatology clinic of the University Hospital of Obstetrics and Gynecology, Sofia, 2019., Methods: Two groups of infants without contact between them were diagnosed with RSV-infection: 14 infants were treated in the Department for healthy newborns - Group 1, and 7 preterm infants were treated in the Neonatal Intensive Care Unit (NICU) - Group 2. The detection of RSV was performed using Real-Time PCR in nasal/throat swabs., Results: Respiratory symptoms occurred 2-5 days after discharge in 14 of 148 healthy term infants born February 5 to 18, 2019; 12 babies were re-hospitalized with LRTI and recovered in a few days. RSV-PCR was positive in 6 infants, while in the others, RSV etiology was suggested, due to similar symptoms and contact between them. The first NICU patient with RSV-LRTI was one of the 26 gestational weeks (GW) twins, who had severe BPD. The other twin was always discharged home without LRTI-symptoms. In the period February 19 to March 15, 2019, 26 premature babies born at 26-34 GW, were tested for RSV (33 nasal/throat swabs). They received a first or subsequent palivizumab injection. We identified 11 positive samples in 7 of the babies. Despite the clinical recovery, the second RSV-PCR remained positive in 4 babies. Six of the 7 NICU patients had symptoms of LRTI, and two of them needed mechanical ventilation. Six babies were discharged home after stabilization, one was transferred to the Pediatric department for further treatment of BPD and later discharged too., Conclusions: This was the most serious outbreak of RSV infections in neonates since the RSV-PCR diagnostic in Bulgaria was introduced. The course of RSV-LRTI was severe in extremely preterm patients with underlying BPD. So, routine in-hospital RSV-prophylaxis with palivizumab should be considered for infants at the highest risk., (© 2021. The Author(s).)

Introduction: This study aimed to investigate the trend and seasonality of infection due to respiratory syncytial virus (RSV) at KK Women's and Children's Hospital (KKH) in Singapore and to examine the risk factors for mortality among children with RSV infection requiring admission to the paediatric intensive care unit (PICU)., Methods: A retrospective study was conducted at KKH on children with RSV infections who were admitted to the PICU between January 2004 and December 2010. The medical records of children who died from RSV infections were reviewed. Linear regression was performed to determine the risk factors for RSV mortality., Results: RSV infection was documented in 5,785 children during the study period; the infection was noted to be occurring throughout the year, with a small increase in prevalence between the months of June and August every year. Among 85 (1.5%) out of 5,785 children who were admitted to the PICU for RSV infection, 74 (1.3%) survived and 11 (0.2%) died. Multivariate logistic regression analysis showed that haemodynamically significant cardiac disease (odds ratio [OR] 12.2, 95% confidence interval [CI] 0.9-16.7, p = 0.05), immunodeficiency (OR 71.4, 95% CI 8.2-500, p < 0.001) and metabolic disease (OR 71.4, 95% CI 4.3-1,000, p = 0.003) were independent risk factors for mortality in RSV infections. Prematurity increased the risk of admission to the PICU but was not significantly associated with mortality., Conclusion: Children with haemodynamically significant cardiac disease, immunodeficiency and metabolic disease were at higher risk of death after hospitalisation for RSV-related illnesses. These children should be considered for palivizumab prophylaxis., (Copyright: © Singapore Medical Association.)

Infants and older adults are especially vulnerable to infection by respiratory syncytial virus (RSV), which can cause significant illness and irreparable damage to the lower respiratory tract and for which an effective vaccine is not readily available. Palivizumab, a recombinant monoclonal antibody (mAb), is an approved therapeutic for RSV infection for use in high-risk infants only. Due to several logistical issues, including cost of goods and scale-up limitations, palivizumab is not approved for other populations that are vulnerable to severe RSV infections, such as older adults. In this study, we demonstrate that intranasal delivery of adeno-associated virus serotype 9 (AAV9) vector expressing palivizumab or motavizumab, a second-generation version of palivizumab, significantly reduced the viral load in the lungs of the BALB/c mouse model of RSV infection. Notably, we demonstrate that AAV9 vector-mediated prophylaxis against RSV was effective despite the presence of serum-circulating neutralizing AAV9 antibodies. These findings substantiate the feasibility of repeatedly administering AAV9 vector to the airway for seasonal prophylaxis against RSV, thereby expanding the application of vectored delivery of mAbs as an effective prophylaxis strategy against various airborne viruses.

Abstract: Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in infants and young children. Monthly administration of palivizumab during the RSV season is effective in preventing severe infections in children with comorbidities. However, determining the onset of the RSV season for starting palivizumab is often challenging. The present study aimed to evaluate the ideal timing to start palivizumab and its effect on hospitalization in the real world.We performed a retrospective, observational study to identify the relationship between the timing of the first dose of palivizumab administration and RSV-related hospitalization. Medical records from 2015 to 2019 were reviewed. We included patients who had indications for palivizumab as of July 1 in each year. We counted the proportion of children receiving palivizumab and the number of RSV infection-related hospitalizations each month. We also evaluated the differences in background and underlying disease between children with and without hospitalization.A total of 498 patients were included, and 105 (21.0%) completed the first dose in July when the RSV season usually begins in Japan. Twenty-three (4.6%) patients were hospitalized for RSV infection during the observation period, with 13 (56.5%) hospitalizations before their first dose of palivizumab. The remaining 10 patients were hospitalized after receiving 1 or more doses of palivizumab. Children living with siblings and children with cyanosis originating from congenital heart disease had a higher risk of RSV with odds ratios of 5.1 (95% confidence interval 1.48-17.6, P < .01) and 3.3 (95% confidence interval 1.33-7.94, P < .01), respectively.Delays in administering palivizumab at the beginning of the season increases the rate of RSV infection-related hospitalization. To maximize prophylactic effectiveness, administering the first dose as early as possible in the RSV season is crucial, with priority for cyanotic children or those with siblings., Competing Interests: Kenji Furuno received speaker honoraria from AbbVie GK. The other authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children., Objectives: To assess the effects of palivizumab for preventing severe RSV infection in children., Search Methods: We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021., Selection Criteria: We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history.  DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days., Main Results: We included five studies with  a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low.  Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; 5 studies, 3343 participants; moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). Palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence)., Authors' Conclusions: The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW., Methods: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians., Results: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions., Conclusions: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.

Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations., (© 2021. The Author(s).)

Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit., Competing Interests: SE: Research support from GSK, Sanofi, and Vifor. Speaker’s fees from GSK, Janssen, Pfizer, Novartis, Sanofi Pasteur, and MSD in the past 3 years. BA is supported by the Canadian Health and Research Institute Vanier Canada scholarship. PB received grants for epidemiological and HTA research projects from GlaxoSmithKline, MSD, Sanofi Pasteur, Pfizer, Seqirus and Astra Zeneca, and fees for taking part in advisory boards on different vaccines from the same companies plus Janssen. FM has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FM has also acted as principal investigator in RCTs of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbot, Novavax, and Medimmune, with honoraria paid to his institution. FM research activities received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER and project Enterogen (ISCIII/PI19/01090). KF is a member of the Australian Technical Advisory Group on Immunisation (ATAGI) but the views in this manuscript are her own and not necessarily those of ATAGI. KF has received honoraria as a member of the vaccine advisory boards for Seqiris and Sanofi Pasteur in the last 5 years. AM has received research grants from NIH, Janssen and Merck AND fees for participation in advisory boards from Janssen, Sanofi-Pasteur, Merck and Roche. MS reports research grants and personal fees for advisory boards from GSK, Pfizer, Sanofi-Pasteur, Janssen and Seqirus. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Esposito, Abu-Raya, Bonanni, Cahn-Sellem, Flanagan, Martinon Torres, Mejias, Nadel, Safadi and Simon.)

To date, there is no consensus regarding palivizumab prophylaxis for respiratory syncytial virus infection. The purpose of this study is to assess the effectiveness of palivizumab prophylaxis to prevent respiratory syncytial virus-related infection consultations and hospitalizations in high-risk children <2 y. We studied children <2 y of age with risk factors who had indication of palivizumab prophylaxis over eight epidemic seasons (2011-2012 to 2018-2019) in Navarra, Spain. Children positives for respiratory syncytial virus by reverse-transcription polymerase chain reaction were compared to negative testers. Palivizumab was indicated in 1,214 children <2 y of age with risk factors during 2011-2012 to 2018-2019 seasons. A total of 142 high-risk children tested for respiratory syncytial virus were included in the study. From the 35 respiratory syncytial virus-positive confirmed cases, 20 (57%) had received palivizumab versus 82 (77%) from the 107 negative controls. The effectiveness of prophylactic palivizumab was 70% (95% CI, 19%-90%) in preventing confirmed clinical infection and 82% (95% CI, 29%-96%) in preventing hospitalized cases. Our results show that palivizumab is notably effective for preventing laboratory-confirmed cases of respiratory syncytial virus and hospitalization in high-risk children <2 y of age. For children who have received palivizumab, the risk of getting sick remains high; thus, other preventive measures are necessary.

Palivizumab is the only licensed respiratory syncytial virus (RSV) immunoprophylaxis (IP) available to prevent severe RSV disease in high-risk pediatric populations, including infants born at 29-34 weeks' gestational age (wGA). In 2014, the American Academy of Pediatrics (AAP) stopped recommending RSV IP use for otherwise healthy 29-34 wGA infants and stated that 29-34 wGA infants and term infants have similar RSV hospitalization (RSVH) rates. This study aimed to compare RSV IP use and RSVH rates in 29-34 wGA infants and term infants during the 3 RSV seasons before and after the 2014 AAP policy change. RSV IP use in otherwise healthy infants 29-30, 31-32, and 33-34 wGA was estimated from pharmacy or outpatient medical claims for palivizumab. RSVH rates in the first 6 months of life were calculated per 100 infant-seasons. RSVH rate ratios were used to compare preterm infants and term infants before and after the policy change. Across infant cohorts (29-34 wGA) and chronologic age groups (<3 months and 3-<6 months), absolute decreases in RSV IP use between the combined 2011-2014 seasons and 2014-2017 seasons ranged from 7% to 38% and from 68% to 97%, respectively. Compared with 2011-2014, the RSVH risk increased 2.09-fold ( P < .001) and 1.76-fold ( P < .001) in 2014-2017 for infants born at 29-34 wGA and aged <6 months with commercial and Medicaid insurance, respectively. Overall, RSV IP use declined in the RSV seasons following the 2014 RSV IP policy change, and RSVH increased among 29-34 wGA infants aged <6 months.