Effectiveness of a Second Dose of an mRNA Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in Individuals Previously Infected by Other Variants.

BACKGROUND: Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown. METHODS: We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18-64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan-Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021. RESULTS: In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2-66.4%) 7-34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1-69.9%) for mRNA-1273 and 52.0% (41.8-63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4-89.9%), 66.1% (54.9-77.5%), and 60.2% (55.5-64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (-55.3% to 81.1%). CONCLUSIONS: Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant.

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data.

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations.

Influenza hospitalisations in Spain between the last influenza and COVID-19 pandemic (2009-2019).

Knowing the burden of severe disease caused by influenza is essential for disease risk communication, to understand the true impact of vaccination programmes and to guide public health and disease control measures. We estimated the number of influenza-attributable hospitalisations in Spain during the 2010-2011 to 2019-2020 seasons - based on the hospitalisations due to severe acute respiratory infection (SARI) in Spain using the hospital discharge database and virological influenza information from the Spanish Influenza Sentinel Surveillance System (SISSS). The weekly numbers of influenza-attributable hospitalisations were calculated by multiplying the weekly SARI hospitalisations by the weekly influenza virus positivity, obtained from the SISSS in each season, stratified by age group and sex. The influenza-related hospitalisation burden is age-specific and varies significantly by influenza season. People aged 65 and over yielded the highest average influenza-attributable hospitalisation rates per season (615.6 per 100,000), followed by children aged under 5 (251.2 per 100,000). These results provide an essential contribution to influenza control and to improving existing vaccination programmes, as well as to the optimisation and planning of health resources and policies.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

Assessing the effect of non-pharmaceutical interventions on COVID-19 transmission in Spain, 30 August 2020 to 31 January 2021.

BackgroundAfter a national lockdown during the first wave of the COVID-19 pandemic in Spain, regional governments implemented different non-pharmaceutical interventions (NPIs) during the second wave.AimTo analyse which implemented NPIs significantly impacted effective reproduction number (Rt) in seven Spanish provinces during 30 August 2020-31 January 2021.MethodsWe coded each NPI and levels of stringency with a 'severity index' (SI) and computed a global SI (mean of SIs per six included interventions). We performed a Bayesian change point analysis on the Rt curve of each province to identify possible associations with global SI variations. We fitted and compared several generalised additive models using multimodel inference, to quantify the statistical effect on Rt of the global SI (stringency) and the individual SIs (separate effect of NPIs).ResultsThe global SI had a significant lowering effect on the Rt (mean: 0.16 ± 0.05 units for full stringency). Mandatory closing times for non-essential businesses, limited gatherings, and restricted outdoors seating capacities (negative) as well as curfews (positive) were the only NPIs with a significant effect. Regional mobility restrictions and limited indoors seating capacity showed no effect. Our results were consistent with a 1- to 3-week-delayed Rt as a response variable.ConclusionWhile response measures implemented during the second COVID-19 wave contributed substantially to a decreased reproduction number, the effectiveness of measures varied considerably. Our findings should be considered for future interventions, as social and economic consequences could be minimised by considering only measures proven effective.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

[Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination]. / Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted Odds Ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and, 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

No effect modification of influenza virus vaccine effectiveness by age or chronic condition was observed in the 2010/11 to 2017/18 seasons.

PURPOSE: Most European influenza vaccine strategies target individuals at higher risk of complications, which include, among others, individuals aged ≥65 years and with chronic conditions. These individuals not only have a high-risk of post-infection complications but also could have lower capacity of acquiring adequate vaccine-induced protection. As such, chronic conditions and age could modify the effect of vaccines. This study aimed at assessing the potential effect modification of influenza vaccine effectiveness (IVE) by age and chronic conditions. METHODS: We used eight-season data from the Portuguese vaccine effectiveness study. Every season, physicians at primary care units recruited patients with influenza-like illness. Clinical data and swabs were collected for Reverse Transverse Polymerase Chain Reaction (RT-PCR) detection of influenza. Trivalent inactivated IVE was estimated as 1 - odds ratio (OR) of being vaccinated in cases (RT-PCR positive for influenza) versus negative controls. ORs were obtained using a multivariable conditional logistic regression model, paired by week of onset within each season. Confounders were assessed by designing a specific causal diagram. Age (< 65 or ≥65 years) and chronic conditions (diabetes, cardiovascular disease, chronic renal disease, chronic hepatic disease, obesity, chronic respiratory disease, and congenital or acquired immunodeficiency) were studied as effect modifiers by including an interaction term in the regression models. Significance was established at 5%. RESULTS: Point estimates indicate a higher IVE in the chronic condition strata compared to that in the no chronic condition strata. Regarding age, different results were obtained considering the virus type and (sub)type. When comparing the ≥65 years with the <65 years of age strata, we observed a higher IVE against A(H1N1)pdm09, an equal IVE against A(H3N2) and a lower IVE against B virus. However, all interaction terms were statistically insignificant, and this may be due to a small sample size. CONCLUSION: The potential effect modification of age or chronic condition was not observed within our study.

Effectiveness of mRNA COVID-19 vaccines in preventing SARS-CoV-2 infections and COVID-19 hospitalisations and deaths in elderly long-term care facility residents, Spain, weeks 53 2020 to 13 2021.

Residents in long-term care facilities (LTCF) experienced a large morbidity and mortality during the COVID-19 pandemic in Spain and were prioritised for early COVID-19 vaccination. We used the screening method and population-based data sources to obtain estimates of mRNA COVID-19 vaccine effectiveness for elderly LTCF residents. The estimates were 71% (95% CI: 56-82%), 88% (95% CI: 75-95%), and 97% (95% CI: 92-99%), against SARS-CoV-2 infections (symptomatic and asymptomatic), and COVID-19 hospitalisations and deaths, respectively.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021.

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45-74) for one dose only and 89% (95% CI: 79-94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Illness Severity in Hospitalized Influenza Patients by Virus Type and Subtype, Spain, 2010-2017.

We conducted a retrospective cohort study to assess the effect of influenza virus type and subtype on disease severity among hospitalized influenza patients in Spain. We analyzed the cases of 8,985 laboratory-confirmed case-patients hospitalized for severe influenza by using data from a national surveillance system for the period 2010-2017. Hospitalized patients with influenza A(H1N1)pdm09 virus were significantly younger, more frequently had class III obesity, and had a higher risk for pneumonia or acute respiratory distress syndrome than patients infected with influenza A(H3N2) or B (p<0.05). Hospitalized patients with influenza A(H1N1)pdm09 also had a higher risk for intensive care unit admission, death, or both than patients with influenza A(H3N2) or B, independent of other factors. Determining the patterns of influenza-associated severity and how they might differ by virus type and subtype can help guide planning and implementation of adequate control and preventive measures during influenza epidemics.

Evaluating the impact of the weather conditions on the influenza propagation.

BACKGROUND: Predicting the details of how an epidemic evolves is highly valuable as health institutions need to better plan towards limiting the infection propagation effects and optimizing their prediction and response capabilities. Simulation is a cost- and time-effective way of predicting the evolution of the infection as the joint influence of many different factors: interaction patterns, personal characteristics, travel patterns, meteorological conditions, previous vaccination, etc. The work presented in this paper extends EpiGraph, our influenza epidemic simulator, by introducing a meteorological model as a modular component that interacts with the rest of EpiGraph's modules to refine our previous simulation results. Our goal is to estimate the effects of changes in temperature and relative humidity on the patterns of epidemic influenza based on data provided by the Spanish Influenza Sentinel Surveillance System (SISSS) and the Spanish Meteorological Agency (AEMET). METHODS: Our meteorological model is based on the regression model developed by AB and JS, and it is tuned with influenza surveillance data obtained from SISSS. After pre-processing this data to clean it and reconstruct missing samples, we obtain new values for the reproduction number of each urban region in Spain, every 10 minutes during 2011. We simulate the propagation of the influenza by setting the date of the epidemic onset and the initial influenza-illness rates for each urban region. RESULTS: We show that the simulation results have the same propagation shape as the weekly influenza rates as recorded by SISSS. We perform experiments for a realistic scenario based on actual meteorological data from 2010-2011, and for synthetic values assumed under simplified predicted climate change conditions. Results show that a diminishing relative humidity of 10% produces an increment of about 1.6% in the final infection rate. The effect of temperature changes on the infection spread is also noticeable, with a decrease of 1.1% per extra degree. CONCLUSIONS: Using a tool like ours could help predict the shape of developing epidemics and its peaks, and would permit to quickly run scenarios to determine the evolution of the epidemic under different conditions. We make EpiGraph source code and epidemic data publicly available.

Environmental drivers, climate change and emergent diseases transmitted by mosquitoes and their vectors in southern Europe: A systematic review.

Mosquito borne diseases are a group of infections that affect humans. Emerging or reemerging diseases are those that (re)occur in regions, groups or hosts that were previously free from these diseases: dengue virus; chikungunya virus; Zika virus; West Nile fever and malaria. In Europe, these infections are mostly imported; however, due to the presence of competent mosquitoes and the number of trips both to and from endemic areas, these pathogens are potentially emergent or re-emergent. Present and future climatic conditions, as well as meteorological, environmental and demographic aspects are risk factors for the distribution of different vectors and/or diseases. This review aimed to identify and analyze the existing literature on the transmission of mosquito borne diseases and those factors potentially affecting their transmission risk of them in six southern European countries with similar environmental conditions: Croatia, France, Greece, Italy, Portugal and Spain. In addition, we would identify those factors potentially affecting the (re)introduction or spread of mosquito vectors. This task has been undertaken with a focus on the environmental and climatic factors, including the effects of climate change. We undertook a systematic review of the vectors, diseases and their associations with climactic and environmental factors in European countries of the Mediterranean region. We followed the PRISMA guidelines and used explicit and systematic methods to identify, select and critically evaluate the studies which were relevant to the topic. We identified 1302 articles in the first search of the databases. Of those, 160 were selected for full-text review. The final data set included 61 articles published between 2000 and 2017.39.3% of the papers were related with dengue, chikungunya and Zika virus or their vectors. Temperature, precipitation and population density were key factors among others. 32.8% studied West Nile virus and its vectors, being temperature, precipitation and NDVI the most frequently used variables. Malaria have been studied in 23% of the articles, with temperature, precipitation and presence of water indexes as the most used variables. The number of publications focused on mosquito borne diseases is increasing in recent years, reflecting the increased interest in that diseases in southern European countries. Climatic and environmental variables are key factors on mosquitoes' distribution and to show the risk of emergence and/or spread of emergent diseases and to study the spatial changes in that distributions.

Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18.

BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over 64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.

Interim 2019/20 influenza vaccine effectiveness: six European studies, September 2019 to January 2020.

BackgroundInfluenza A(H1N1)pdm09, A(H3N2) and B viruses were co-circulating in Europe between September 2019 and January 2020.AimTo provide interim 2019/20 influenza vaccine effectiveness (VE) estimates from six European studies, covering 10 countries and both primary care and hospital settings.MethodsAll studies used the test-negative design, although there were some differences in other study characteristics, e.g. patient selection, data sources, case definitions and included age groups. Overall and influenza (sub)type-specific VE was estimated for each study using logistic regression adjusted for potential confounders.ResultsThere were 31,537 patients recruited across the six studies, of which 5,300 (17%) were cases with 5,310 infections. Most of these (4,466; 84%) were influenza A. The VE point estimates for all ages were 29% to 61% against any influenza in the primary care setting and 35% to 60% in hospitalised older adults (aged 65 years and over). The VE point estimates against A(H1N1)pdm09 (all ages, both settings) was 48% to 75%, and against A(H3N2) ranged from -58% to 57% (primary care) and -16% to 60% (hospital). Against influenza B, VE for all ages was 62% to 83% (primary care only).ConclusionsInfluenza vaccination is of continued benefit during the ongoing 2019/20 influenza season. Robust end-of-season VE estimates and genetic virus characterisation results may help understand the variability in influenza (sub)type-specific results across studies.

Excess all-cause mortality during the COVID-19 pandemic in Europe - preliminary pooled estimates from the EuroMOMO network, March to April 2020.

A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.

First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Understanding influenza vaccination among Portuguese elderly: the social ecological framework.

This study intended to identify and quantify the social ecological model (SEM) levels associated to seasonal IV uptake in the Portuguese elderly population. Data from the 2014 National Health Survey was restricted to individuals aged 65+ years (n = 5669). Twenty-three independent variables were allocated to the SEM levels: individual, interpersonal, organizational, community and policy. Sex stratified and age adjusted analysis using Poisson regression were performed for each level and for a fitted full model. Relative reduction in pseudo R magnitude measured marginal contribution of each level. For men and women, older groups (85+ vs. 65-69; men, PR = 1.59 and women, PR = 1.56); having 3+ chronic conditions (men, PR = 1.39 and women, PR = 1.35); previous 4 weeks GP and outpatient visits were associated to higher IV uptake. For men, only 2 SEM levels were associated (individual and organizational) while for women the community level was also relevant. Main marginal contribution came from individual (17.9% and 16.3%) and organizational (30.7% and 22.7%) levels. This study highlights the importance of individual characteristics, access and use of health care services for the IV uptake and the sex differential behaviour.

Impact of national influenza vaccination strategy in severe influenza outcomes among the high-risk Portuguese population.

BACKGROUND: All aged individuals with a chronic condition and those with 65 and more years are at increased risk of severe influenza post-infection complications. There is limited research on cases averted by the yearly vaccination programs in high-risk individuals. The objective was to estimate the impact of trivalent seasonal influenza vaccination on averted hospitalizations and death among the high-risk population in Portugal. METHODS: The impact of trivalent seasonal influenza vaccination was estimated using vaccine coverage, vaccine effectiveness and the number of influenza-related hospitalizations and deaths. The number of averted events (NAE), prevented fraction (PF) and number needed to vaccinate (NVN) were estimated for seasons 2014/15 to 2016/17. RESULTS: The vaccination strategy averted on average approximately 1833 hospitalizations and 383 deaths per season. Highest NAE was observed in the ≥65 years population (85% of hospitalizations and 95% deaths) and in the 2016/17 season (1957 hospitalizations and 439 deaths). On average, seasonal vaccination prevented 21% of hospitalizations in the population aged 65 and more, and 18.5% in the population with chronic conditions. The vaccination also prevented 29% and 19.5% of deaths in each group of the high-risk population. It would be needed to vaccinate 3360 high-risk individuals, to prevent one hospitalization and 60,471 high-risk individuals to prevent one death. CONCLUSION: The yearly influenza vaccination campaigns had a sustained positive benefit for the high-risk population, reducing hospitalizations and deaths. These results can support public health plans toward increased vaccine coverage in high-risk groups.