Quadrivalent live attenuated influenza vaccines (LAIV-4) offer an alternative to inactivated influenza vaccines (IIV) for children aged 2-17 years, but data on their comparative effectiveness are limited. This study assessed vaccination rates and real-world effectiveness of LAIV-4 and IIV in preventing influenza and influenza-like illness (ILI) in Italian children during the 2022-2023 and 2023-2024 seasons. We conducted a population-based cohort study of children aged 2-14 years from September 2022 to April 2024, using data from Pedianet, a pediatric primary care database of anonymized records from family pediatricians. Children vaccinated with LAIV-4 or IIV were compared to unvaccinated children. The primary outcome was any first influenza or ILI episode. Monthly vaccination incidence rates per 1000 person-months were calculated for each vaccine type. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for vaccine effectiveness (VE) were estimated using adjusted mixed-effects Cox models. A total of 65,545 (472,173 person-months) and 72,377 (527,348 person-months) children were included for the 2022-2023 and 2023-2024 seasons, respectively. Vaccination rates were 12.71 and 12.85 per 1000 person-months, respectively. Compared to unvaccinated children, LAIV-4 had an overall effectiveness of 43 % (95 % CI, 32 %-53 %), while IIV effectiveness was 54 % (95 % CI, 46 %-61 %). In 2022-2023, LAIV-4 (38 % [95 % CI, 12 %-56 %]) and IIV (49 % [95 % CI, 37 %-58 %]) had comparable effectiveness. In 2023-2024, LAIV-4 (40 % [95 % CI, 25 %-52 %]) was slightly less effective than IIV (58 % [95 % CI, 44 %-68 %])(p = 0.048). An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed.

To evaluate the sociodemographic and socioeconomic factors impacting pediatric influenza vaccination coverage in Italy. This retrospective observational cohort study included all children aged 6 months to 14 years at the start of the five consecutive seasons (September 1, 2019, to January 31, 2024) who were enrolled in the Pedianet network, a comprehensive database comprising over 200 family pediatricians in Italy. Generalized linear mixed-effects models were used to analyze the association between children's sex, age group (6 months-6 years, 7-11 years, 12-14 years), sibling status, area of birth, Area Deprivation Index (ADI), presence of comorbidities, and vaccination coverage across seasons. Influenza vaccination coverage remained suboptimal across all seasons considered, with a minimum of 7 % in 2019/2020 and a peak of 12 % during the 2020/2021 season. The likelihood of vaccination decreased with increasing age, while children with at least one sibling and those residing in Central or Southern Italy and the Islands were more likely to be vaccinated. Beginning with the 2020/2021 season, our results demonstrate a significantly lower likelihood of vaccination among children from more deprived areas. No significant differences were observed between males and females. Our findings enhance the understanding of the sociodemographic factors influencing influenza vaccination coverage among Italian children. Considering the role and complexity of these determinants is essential for developing tailored vaccination strategies to improve coverage in the future.

Background and objectives Quadrivalent live attenuated influenza vaccines (LAIV-4) offer an alternative to inactivated influenza vaccines (IIV) for children aged 2-17 years, but data on their comparative effectiveness are limited. This study assessed vaccination rates and real-world effectiveness of LAIV-4 and IIV in preventing influenza and influenza-like illness (ILI) in Italian children during the 2022-2023 and 2023-2024 seasons. Methods We conducted a population-based cohort study of children aged 2-14 years from September 2022 to April 2024, using data from Pedianet, a pediatric primary care database of anonymized records from family pediatricians. Children vaccinated with LAIV-4 or IIV were compared to unvaccinated children. The primary outcome was any first influenza or ILI episode. Monthly vaccination incidence rates per 1,000 person-months were calculated for each vaccine type. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for vaccine effectiveness (VE) were estimated using adjusted mixed-effects Cox models. Results A total of 65,545 (472,173 person-months) and 72,377 (527,348 person-months) children were included for the 2022-2023 and 2023-2024 seasons, respectively. Vaccination rates were 12.71 and 12.85 per 1,000 person-months, respectively. Compared to unvaccinated children, LAIV-4 had an overall effectiveness of 43% (95% CI, 32%-53%), while IIV effectiveness was 54% (95% CI, 46%-61%). In 2022-2023, LAIV-4 (38% [95% CI, 12%-56%]) and IIV (49% [95% CI, 37%-58%]) had comparable effectiveness. In 2023-2024, LAIV-4 (40% [95% CI, 25%-52%]) was slightly less effective than IIV (58% [95% CI, 44%-68%])(p=0.048). Conclusions An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed. Article Summary A retrospective population-based cohort analysis showing moderate effectiveness of live attenuated influenza vaccines (LAIVs) in preventing influenza/influenza-like-illness in Italian children. What’s Known on This Subject There is conflicting evidence on the effectiveness of the quadrivalent live attenuated influenza vaccine LAIV (LAIV-4) in the pediatric population. What This Study Adds This population-based study assesses the effectiveness of LAIVs against influenza/influenza-like illness (ILI) among children in Italy in the post-COVID-19 influenza seasons using real-world data. Our findings document moderate protection provided by LAIVs against influenza/ILI in the 2022-2023 and 2023-2024 seasons. Contributors Statement Page Dr. Vera Rigamonti performed the statistical analysis, interpreted the results, and drafted the initial manuscript; Dr. Vittorio Torri conceptualized and designed the artificial intelligence algorithms; Dr. Daniele Donà contributed to data interpretation; Drs Anna Cantarutti and Costanza Di Chiara, designed the study, contributed to the analysis plan, interpreted the results, supervised the project, and contributed to the manuscript writing; Profs. Shaun K Morris, Francesca Ieva, and Carlo Giaquinto interpreted the results and critically reviewed the manuscript for important intellectual content. All authors reviewed, edited, and approved the final version of the manuscript, authorized its submission for publication, and agree to be accountable for all aspects of the work.

Purpose Nirsevimab and the maternal vaccination in pregnancy are newly introduced prevention strategies against respiratory syncytial virus (RSV). This study evaluated pediatricians’ knowledge, attitudes, and barriers to RSV immunization in Italy and Cyprus/Greece, where nirsevimab had not yet been implemented, and in Spain, where it was introduced in 2023/2024. Methods A survey was distributed to pediatricians across Spain, Italy, and Cyprus/Greece in July-August/2024. Occupational characteristics, and knowledge, attitudes and practices toward palivizumab, nirsevimab, and the maternal vaccine were collected. Of 578 respondents (response rate=19.3%), 50% were from Spain, 40% from Italy, and 10% from Cyprus/Greece. As 90% of responses came from Spain and Italy, the main analysis focused on these two countries. Descriptive and univariate analyses (Chi-square or Fisher’s exact tests) were conducted. Results Respondents included pediatricians from community (51.7%), tertiary (30.4%), and primary/secondary care (17.9%) settings. Pediatricians were generally aware of RSV risk factors, without differences across countries. However, 245 (55.9%) and 375 (86.0%) participants reported average-to-low knowledge of nirsevimab and the maternal vaccine, respectively, with differences across countries (p=0.002). Despite limited knowledge, 311 (85.9%) pediatricians were willing to administer nirsevimab, and 319 (92.2%) supported its use for all infants. Nirsevimab administration’s barriers, including unfamiliarity and logistical challenges, were cited by 69 (20.0%) pediatricians. Regarding immunization preferences, 165 (47.4%) pediatricians were very likely to support the maternal vaccine over nirsevimab. Conclusions While pediatricians support RSV immunization, knowledge gaps and logistical barriers may hinder early-stage implementation. Optimizing education on RSV immunization will be crucial to improve uptake and prevention strategies. What’s Known on This Subject There is limited evidence regarding pediatricians’ attitudes and knowledge of nirsevimab and maternal RSV vaccination during pregnancy. What This Study Adds This multi-country survey evaluates pediatricians’ knowledge, attitudes, and barriers to RSV immunization in Italy and Cyprus/Greece, where nirsevimab had not yet been implemented, and in Spain, where it was introduced in 2023/2024.

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for acute respiratory tract infection (ARTI) in young children. Respiratory viral coinfections are frequently identified in RSV-related ARTIs, yet their impact on disease severity remains controversial and may vary according to the co-pathogen involved. In the context of evolving RSV prevention strategies, a clearer understanding of RSV coinfection phenotypes is needed. Methods: We conducted a multicenter retrospective cohort study of children aged ≤ 5 years hospitalized for ARTI at two Italian tertiary-care pediatric hospitals between 1 September 2022 and 30 April 2025. Children with laboratory-confirmed RSV infection detected by multiplex polymerase chain reaction were included. Patients were classified as having RSV monoinfection, RSV–rhinovirus coinfection, or RSV–non-rhinovirus coinfection. Severe disease was defined as a composite outcome including intensive care unit (ICU) admission, need for respiratory or hemodynamic support, or death. Association between infection status and severe disease was evaluated using a Poisson regression model with robust variance, adjusted for age, sex, and comorbidities. Results: Among 231 RSV-related hospitalizations, 118 (51.1%) were classified as RSV monoinfection, 65 (28.1%) as RSV–rhinovirus coinfection, and 48 (20.8%) as RSV–non-rhinovirus coinfection. Children with RSV–rhinovirus coinfection were older and had shorter hospital stays. Severe disease occurred in 80.5% of RSV monoinfections, 70.8% of RSV–rhinovirus coinfections, and 75.0% of RSV–non-rhinovirus coinfections. After adjustment, neither RSV–rhinovirus coinfection (adjusted risk ratio [aRR]: 0.93; 95% confidence interval [95% CI]: 0.80–1.13) nor RSV–non-rhinovirus coinfection (aRR: 0.99; 95% CI: 0.83–1.18) was associated with increased disease severity compared with RSV monoinfection. Conclusions: RSV–rhinovirus and RSV–non-rhinovirus coinfections were not associated with greater disease severity compared with RSV monoinfection in hospitalized children. These findings support pathogen-specific interpretation of multiplex diagnostic results and inform clinical risk stratification in the era of expanding RSV prevention strategies.