The present study describes the trend of pediatric influenza vaccination coverage rates in Italy at national and regional level across eleven seasons (2010/11–2020/21) and assess the impact of the COVID-19 pandemic on the variation of vaccination coverage between the seasons 2019/20–2020/21. Results showed that the coverage trend in Italy in the timeframe considered remains low, with relevant differences across regions and seasons, and a general increase in coverage in the last 2020/21 season, probably due to the higher willingness from parents to vaccinate their children to protect them from influenza and facilitate the differential diagnosis with COVID-19. Consistent differences were also observed across regions in the implementation of the Italian Ministry of Health Circular for the extension of the free influenza vaccination to healthy children aged between 6 months and 6 years. Finally, a reduction of ILI and the absence of identified influenza cases during 2020/21 season were also reported, likely determined by the massive use of face masks, hand hygiene and social distancing due to the implementation of containment measures related to COVID-19 [
23]. Influenza vaccination is a key preventive measure in reducing the clinical burden of disease, in terms of cases, hospitalizations, and deaths, and its associated costs both in children and adults [
24,
25]. These costs are composed of direct ones related to medical visits, hospitalizations and medicines, but also indirect ones such as loss of productivity, with psychological and social impact for parents who see their children ill [
26]. Moreover, and especially in Italy, the burden of influenza is related to children who stay a long time with their grandparents and consequently these elderlies become at a high risk of getting influenza by their nephews. In this context and for the indirect protection of their caregivers, children are undoubtedly an important target for influenza vaccination [
27]. Analyzing the whole period taken as a reference in our study (2010–2021), a non-linear trend over time in pediatric coverage can be observed and, despite some increases recorded in few seasons, it remains generally low. In detail, a progressive decrease was observed from 2010 to 2016, with a significant collapse in coverage in the 2014/15 and 2015/16 seasons. The reasons behind this collapse could not be identified with certainty, but inappropriate communication by media and healthcare workers around influenza vaccination could be associated to it. In particular, a national misinformation episode on influenza elderly vaccination happened in November 2014 could have had an impact also on vaccination for children. It refers to a suspension as a precautionary measure by the Italian Medicines Agency (AIFA) of the use of two batches of an influenza adjuvate vaccine after three post-vaccination deaths reported through the Network of Pharmacovigilance and initially associated to the vaccination [
28]. Unfortunately, the media did not emphasize the issue of European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee statement denying the association and the impact of this misinformation in the general population remained so consistent that had a relevant aftermath also on the following influenza vaccination season [
29].
After the two critical seasons of 2014/15 and 2015/16, a gradual increase in coverage was observed, reaching in the last 2020/21 season significantly higher values, in contrast with the results by Fogel et al. [
30], who found a decline in influenza vaccination rates in children during the COVID-19 pandemic, probably due to lack of confidence and inconvenience by parental intent to obtain the influenza vaccine or introduced barriers to healthcare access. As initially mentioned, reasons for the increase seen in Italy could be instead attributed to a greater attention and sensitivity to respiratory infectious diseases preventable with vaccination derived during the COVID-19 pandemic. In a timeframe when COVID-19 vaccination was not available to the general population yet, the importance of allowing differential diagnosis with respiratory infections other than the one caused by SARS-CoV-2 was essential at every age. Indeed, for this reason the Italian Ministry of Health extended the active and free offer of influenza vaccination to the pediatric population aged 6 months to 6 years and no longer only to the risk categories. However, unfortunately this kind of recommendation has not been renewed in the Italian Ministry of Health Circular for the current season 2021/22, and only some Regions (e.g. Lazio) have kept the gratuity anyway [
31,
32], contributing to the increase of inequalities in healthcare and in the vaccination offer in the country [
33,
34]. Another important aspect of the present study deals actually with the regional differences regarding pediatric coverage, highlighted in the 2019/20 season but that seem noticeable also in the last examined season (2020/21). Despite an increase in recent years, vaccination coverage among all the Italian regions is still rather low. In general, the most performant Regions were Tuscany and Apulia, while Liguria was able to increase the vaccination coverage to 50% only in the age group 2–4. Evidence for these differences is not clearly found in literature, but it is supposed that the network of family pediatricians and their organizational aspect in these Regions are more efficient than in others [
35]. For example, the opening of their clinics in the weekends or for additional hours during the week in order to vaccinate as many children as possible could be reasons for this phenomenon. Other examples to be considered aiming at increasing vaccination coverage are special events where vaccination is combined with health education and promotion activities facilitated by a multidisciplinary team of doctors, nurses, and cultural mediators, as carried out in Emilia Romagna region in some integrated primary care centers [
36]. This kind of activities allows greater proximity to the local community as well. On the other hand, among the Regions with the lowest coverage rates there is the autonomous province of Bolzano, where the population confirmed to be unwilling to vaccinate especially for the pediatric age [
37], despite the local government commitment to promote vaccination (i.e. extending influenza vaccination for free to the entire population). Looking at the European scenario, the comparison of Italian national influenza vaccination trends with other countries is a difficult matter. Data are in fact often unavailable for most countries and, if available, not updated. Exception is made by the United Kingdom, where since 2012 began the phased roll-out of the national influenza vaccination programme to ultimately cover all 2–16 years old children in the country and coverage rates currently reached over 60% of the target population [
38,
39]. Data updated to 2018 are available also for other few countries of the WHO European Region: Estonia, Latvia, Poland Slovakia, and Slovenia, which reported low rates of vaccination coverage similarly to Italy (4.9, 3.1, 0.85, 1.4 and 0.1%, respectively), and Belarus, Finland, Israel, Malta and Russia, which presented a vaccination coverage > 40% (75.4, 42.5, 18.4, 55.0 and 57.4%, respectively) [
38]. A possible explanation of the different coverage levels might be partly due to the heterogeneity of recommendations from a country to another, making in any case hard the comparative assessment [
40‐
42]. As of 2015, indeed, only eight European countries (i.e. Austria, Finland, Latvia, Malta, Poland, Slovakia, Slovenia and the United Kingdom) recommend influenza vaccination for children, and only Finland, Latvia and the United Kingdom provide it free of charge [
42].
Our study is the first in Italy to analyze regional vaccination coverage and strategies in the pediatric population. Vaccination coverage represents the best available indicator of vaccination strategies, as they provide information on their actual implementation in the area and on the efficiency of the vaccination system. Furthermore, the investigation on the differences of the Italian regions highlights implications related to organizational aspects, even if evidence about these is limited and should be improved. The present study has also the strength of using complete national real-world data, even if their aggregated form impedes quantitative analysis on the factors associated with decreasing or increasing trends. Finally, the scarce availability of data, particularly those related to the regional organizational domain, limited a complete analysis of the topic addressed in the study.