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.