Introduction
In December 2020, almost one year into the coronavirus disease 2019 (COVID-19) pandemic, the first vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), BNT162b2 (Comirnaty®), mRNA-1273 (Spikevax®), ChAdOx1 (Vaxzevria®) and Ad26.COV2-S (JCovden) received early conditional marketing authorisation from the European Medicines Agency (EMA) . These vaccines were developed against the original strain of SARS-CoV-2, used in the initial phase of the vaccination campaign and showed high vaccine effectiveness (VE, ≥95%) that, however, waned over time . The mRNA vaccines (Comirnaty® and Spikevax®) were then deployed as the first booster administered during the Autumn of 2021 and as the second booster in the Spring of 2022 in some countries, prioritising individuals of older age and those with medical underlying conditions, and further extending to other age groups. Four adapted mRNA vaccines targeting Omicron subvariants (Comirnaty® bivalent Original/Omicron BA.1, Comirnaty® bivalent Original/Omicron BA.4-5, Spikevax® bivalent Original/Omicron BA.1, Spikevax® bivalent Original/Omicron BA.4-5) were further authorised and administered from September 2022 onwards for second and third booster vaccination in the European Union/European Economic Area (EU/EEA).
Following the rollout of mass COVID-19 vaccination programmes, real-life VE monitoring started to estimate the level and duration of protection, the VE in specific populations not covered by clinical trials and VE against new emerging genetic variants of SARS-CoV-2 . Rapid availability of this information has been of great value in guiding public health decision-makers to adapt vaccination programmes according to the public health needs. The use of population-based Electronic-Health Registries (EHR) has the advantage of large sample size and being readily available, allowing VE prospective monitoring within a short time frame and with relatively few extra resources. Because of this, EHR has become a core data source for COVID-19 VE studies in many countries .
By the end of 2021, the European Centre for Disease Prevention and Control (ECDC) established the Vaccine Effectiveness, Burden and Impact Studies of COVID-19 and Influenza (VEBIS) project to monitor the effectiveneness of vaccines in real world conditions and to inform public health actions and adaptation of vaccination programmes in the EU/EEA countries. One component of VEBIS is based on estimating VE using routinely collected vaccination and outcome data from EHR . This project is leveraging established vaccination registries and health record databases using the combination of mandatory reporting of the vaccination status into these registries and a unique personal identification number or a unique social security number across health databases as the key for individual level datalinkage, allowing to perform VE studies.
The overall aim of this component of the VEBIS project is to expand the use of electronic health registries accross Europe and to establish robust statistical methods to monitor COVID-19 VE over time as well as to improve the timeliness of reporting of VE estimates across EU/EEA. With this aim, we carried out a multi-country study based on EHR to prospectively provide monthly VE estimates of the complete primary vaccination series, the first, the second, and the third booster dose against COVID-19 hospitalisation and COVID-19-related death, in community-dwelling resident population aged 65 years and over.