Interim analysis of COVID-19 vaccine effectiveness against hospitalisation due to COVID-19 and death using electronic health records in eight European countries : April 2022 to July 2023 : first update.
Date: 2024-04-11
Institutions: European Centre for Disease Prevention and Control
Subjects: Belgium, Denmark, European Economic Area, Italy, Luxembourg, Navarre, Netherlands, Norway, Portugal, coronavirus disease, data collection, disease surveillance, e-Health, impact study, report, research method, standard, tariff agreement, vaccine

TECHNICAL REPORT

Interim analysis of COVID-19 
vaccine effectiveness against 
hospitalisation due to COVID-19 
and death using electronic health 
records in eight European 
countries: first update

April 2022 to July 2023    

www.ecdc.europa.eu

ECDC TECHNICAL REPORT 

Interim analysis of COVID-19 vaccine 
effectiveness against hospitalisation due 
to COVID-19 and death using electronic 
health records in eight European 
countries: first update 

April 2022 to July 2023 

This technical report was commissioned by the European Centre for Disease Prevention and Control (ECDC), as 
part of the activities within Framework Contract (FWC) ECDC/2021/018 ‘Vaccine Effectiveness, Burden and Impact 
Studies (VEBIS) of COVID-19 and Influenza Lot 4’. The report’s production was coordinated by Nathalie Nicolay.  

Authors 
Susana Monge Corella, Mario Fontán-Vela (Instituto de Salud Carlos III, Spain), Anthony Nardone, Alexis Sentís, 
Esther Kissling, James Humphreys (Epiconcept, France), Baltazar Nunes, Irina Kislaya, Constantino Caetano, 
Patricia Soares, Ausenda Machado (Instituto Nacional de Saúde, Portugal), Itziar Casado, Jesús Castilla, Iván 
Martínez-Baz, Aitziber Echeverria (Instituto de Salud Pública y Laboral de Navarra – IdiSNA – CIBERESP, Spain), 
Hanne-Dorthe Emborg, Katrin Finderup, Christian Holm Hansen, Bolette Søborg, Palle Valentiner-Branth (Statens 
Serum Institut, Denmark), Hinta Meijerink, Anja Kristoffersen, Jostein Starrfelt (Norwegian Institute of Public 
Health), Toon Braeye, Izaak Van Evercooren, Joris Van Loenhout, Pierre Hubin (Epidemiology of infectious diseases, 
Sciensano, Brussels, Belgium), Ala'a AlKerwi, Susanne Schmitz (Ministry of Health and Social Security, Directorate 
of Health, Service Epidemiology and Statistics, Luxembourg), Chiara Sacco, Alberto Mateo Urdiales, Massimo 
Fabiani (Istituto Superiore di Sanità, Italy), Brechje de Gier, Susan Hahné (Dutch National Institute for Public Health 
and the Environment – RIVM – the Netherlands). 

The following ECDC staff provided substantial input during the production/revision of the document (alphabetical 
order): Nathalie Nicolay.  

For questions or request of support of additional documents and tables presented in the protocol, please email 
vpd.vpd@ecdc.europa.eu.  

Suggested citation: Interim analysis of COVID-19 vaccine effectiveness against hospitalisation and death in eight 
European countries using electronic health records: first update. Stockholm: ECDC; 2024.  

ISBN 978-92-9498-699-3 
doi: 10.2900/78799 
Catalogue number TQ-05-24-227-EN-N 

© European Centre for Disease Prevention and Control, 2024. 

Reproduction is authorised, provided the source is acknowledged. 

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TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Contents 
Abbreviations ............................................................................................................................................... iv 
Summary ...................................................................................................................................................... 5 
Scope of this document .................................................................................................................................. 6 
Background ................................................................................................................................................... 7 
Overall aim .................................................................................................................................................... 7 
Objectives ..................................................................................................................................................... 7 
Principal objective ..................................................................................................................................... 7 
Secondary objective .................................................................................................................................. 7 
Study design ............................................................................................................................................ 8 
Study setting ............................................................................................................................................ 8 
Data sources ........................................................................................................................................ 8 
Study period ........................................................................................................................................... 10 
Study population .................................................................................................................................... 10 
Definitions .............................................................................................................................................. 10 
Vaccination status ............................................................................................................................... 10 
Outcomes .......................................................................................................................................... 11 
Confounder ........................................................................................................................................ 11 
Comorbidities and health-seeking behaviours ............................................................................................ 11 
Data analysis .......................................................................................................................................... 11 
Methods for pooling estimates ............................................................................................................. 12 
Ethical requirements ............................................................................................................................... 12 
Results ........................................................................................................................................................ 13 
Population characteristics and number of events........................................................................................ 13 
Relative vaccine effectiveness of first, second and third booster against hospitalisation due to COVID-19 ....... 18 
First booster ....................................................................................................................................... 18 
Second booster .................................................................................................................................. 18 
Third booster ..................................................................................................................................... 18 
Sensitivity analysis .............................................................................................................................. 18 
Relative vaccine effectiveness of first, second and third booster against COVID-19-related death ................... 26 
First booster ....................................................................................................................................... 26 
Second booster .................................................................................................................................. 26 
Third booster ..................................................................................................................................... 26 
Sensitivity analysis .............................................................................................................................. 26 
Annex 1. Data sources used in the eight study sites to extract the study variables ............................................. 37 
Annex 2. Methodological details in the different study sites .............................................................................. 39 
Annex 3. Numbers of individuals, COVID-19 related deaths and person-months by eight-week period, between 
April 2022 to July 2023, by age group ............................................................................................................ 44 
Annex 4. Distribution of person-months in the study by covariates, from November 2022* to July 2023 ............... 48 
Annex 5. Results restricted to the six study sites that contributed since the start of the study period ................... 51 

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COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Abbreviations 

EC 
EEA 
EMA 
EHR 
EU 
SARI 
SARS-CoV-2 
VE 
VMP 
rVE 
VEBIS 

  European Commission 
  European Economic Area  
  European Medicines Agency 
  Electronic health records  
  European Union 
  Severe acute respiratory infection 
  Severe acute respiratory syndrome coronavirus 2 
  Vaccine effectiveness 
  Vaccine monitoring platform 
  Relative vaccine effectiveness  
  Vaccine Effectiveness, Burden and Impact Studies 

iv 

 
 
TECHNICAL REPORT 

    COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Summary 

• 

• 
• 

• 

• 

• 

• 

• 

• 

• 

This report presents pooled COVID-19 vaccine effectiveness (VE) estimates for the first, second and third 
booster doses (compared to complete primary vaccination with no booster) against hospitalisation due to 
COVID-19 and COVID-19-related death in resident populations ≥50 years of age living in the community 
in up to eight European countries: Belgium, Denmark, Italy, Luxembourg, Spain (Navarra), Norway, 
Portugal, and the Netherlands.  
This study was undertaken within the Vaccine Effectiveness, Burden and Impact Studies (VEBIS) project.  
Compared to the previous report, this analysis uses the same methodology, extends the study period by 
four month (up to July 2023) and includes two additional countries.  
The study period covered in this report is April 2022 to July 2023. The relative VE of the first, second and 
third booster dose were estimated compared to the effectiveness of complete primary vaccination 
received at least 24 weeks ago (≥24 weeks).  
The number of countries included in the monitoring system varied throughout the observation period, with 
study sites/countries joining or leaving at different times. In addition, the contribution of each site/country to 
the different VE estimates depends on the specific roll-out of successive COVID-19 vaccine booster doses by 
age group and at different calendar periods. 
Compared to complete primary vaccination, the first booster dose rVE against hospitalisation due to 
COVID-19 was mostly ≤50% between April 2022 and July 2023 in all age groups (with a few point 
estimates >50%). It waned 12 weeks after administration and dropped even lower after 24 weeks. In the 
most recent estimate, between June and July 2023, the first booster (mostly administered >24 weeks) 
showed little to no added protection, with rVE ranging between 6% and 27% among the different age 
groups. VE estimates against COVID-19-related mortality were similar, although estimates had high 
uncertainty due to a low number of events, particularly in the groups <65 years. 
Compared to complete primary vaccination, rVE of a second booster restored protection shortly after 
administration in the autumn of 2022 in ≥65-year-olds, to 55–76% against hospitalisation due to COVID-19 
and to 63–85% against COVID-19-related death. RVE also waned with time, falling to ≤50% after 24 weeks. 
In the most recent estimate (June and July 2023), rVE of the second booster ranged between -36 and 31% 
against hospitalisation and between -12 and 29% against mortality ≥24 weeks after administration.  
Compared to complete primary vaccination, rVE of the third booster (administrated from October 2022 
onward in ≥80 years and from November 2022 onwards in ≥65 years) against hospitalisation due to 
COVID-19 was 72% shortly after administration (<12 weeks) in ≥80-year-olds but waned rapidly, being 
low or null beyond 12 weeks of administration. The lower rVE could possibly be related to the higher 
proportion of individuals with comorbidities among those with a third booster (being a population that had 
previously accepted a second booster in the spring of 2022). In ≥80 years, overall rVE against mortality 
was 64% initially (<12 weeks after administration) and waned rapidly thereafter (mostly <50% or even 
with negative point estimates ≥12 weeks after administration with large confidence intervals). VE was null 
for both outcomes in all age groups as of June–July 2023.  
The updated results presented in this report suggest that that vaccination with successive booster doses was 
important for restoring individual protection against COVID-19 hospitalisation in the context of waning VE. 
As of July 2023, most of the relative benefit (i.e. the additional protective effect of a vaccine booster) has 
waned, particularly in individuals ≥80 years, while some low residual relative protection was still observed in 
the 65–79-year-olds for those who received a first or second booster. Although there is uncertainty about 
the timing and the magnitude of the waning of immunity, due to a possible underestimation of the rVE, 
these results clearly support the policy of providing additional boosters periodically to maintain protection, 
especially to those aged ≥80 years, as they have an increased risk of severe outcomes. 
During the autumn of 2022, the effectiveness of third booster doses (in Portugal and Belgium, where 
second boosters had been administered over spring 2022) and second booster doses (in those remaining 
participating countries) were similar. This result suggests that the time since the last dose was more 
important than the total number of doses administered in the level of protection against both COVID-19 
hospitalisation and death. From the perspective of the methods to assess and monitor vaccine 
effectiveness, a strategy focused on the effectiveness of the last ‘seasonal’ dose regardless of previous 
boosters is probably more appropriate for future analyses. 

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COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Scope of this document 

This document reports the results of long-term prospective monitoring of COVID-19 vaccine effectiveness (VE) 
using a multi-country approach based on established electronic health records (EHR) databases in eight 
participating countries.  

From October 2021 to July 2023, the project began with a proof-of-concept relating to the usage of EHR in four 
countries, followed by pilot and prospective monitoring phases in the eventual eight participating countries. 
Different outcomes and age groups were included over time (Table 1). The evolution of the COVID-19 pandemic 
and changes in testing policies and vaccine recommendations required successive adaptations of the study 
protocol. Detailed objectives and methods can be found in the published master protocol [1] .  

This report contains VE estimates among individuals aged 50 years and older against hospitalisation due to 
COVID-19 and COVID-19-related death. Relative VE (rVE) of booster doses was estimated using as reference the 
individuals with complete primary vaccination ≥24 weeks ago without a booster. Since the rVE estimates 
presented in this report measure the additional protective effect of a vaccine booster dose, estimates are often 
lower than those of absolute VE reported elsewhere in the literature. RVE estimates were calculated overall and 
by time since the last dose. The study period runs between April 2022 and July 2023.  

Table 1. Successive steps in the implementation of the study 

Project stage 

Study period  

Study sites 

Study outcome 

Proof of concept 

Oct 2021 to 
Mar 2022 

Denmark, Navarra 
(Spain), Norway, 
Portugal 

Absolute and relative VE 
against hospitalisation, overall 
and by time since the booster 

Age groups 
(years) 

Reference 

≥80 
65–79 

≥80 
65–79 
50–64 
18–49 
5–17 

≥80 
65–79 
50–64 
18–49 
5–17 

≥80 
65–79 
50–64 
18–49 
5–17 

Pilot protocol [2]  

Pilot protocol [2]  

Master protocol 
[1]  

Master protocol 
[1]  

Absolute and relative VE 
against SARS-CoV-2 infection, 
hospitalisation, ICU admission 
and mortality, overall and by 
time since the booster 

Absolute, relative and 
additional VE against 
hospitalisation and mortality, 
overall and by time since the 
booster 

Absolute, relative and 
additional VE against 
hospitalisation and mortality, 
overall and by time since the 
booster 

Relative and additional VE 
against hospitalisation and 
mortality, overall and by time 
since the booster 

≥80 
65–79 
50–64 

Master protocol 
[1]  

Full pilot  

Mar 2022 to 
Apr 2022 

Denmark, Navarra 
(Spain), Norway, 
Portugal 

Prospective 
monitoring pilot I 

Apr 2022 to Jul 
2022 

Denmark, Navarra 
(Spain), Norway, 
Portugal 

Prospective 
monitoring pilot II 

Jul 2022 to 
Nov 2022 

Prospective 
monitoring 

Nov 2022 to 
Dec 2022 

Dec 2022 to 
Feb 2023 

Feb 2023 to 
Jul 2023 

Belgium, Denmark, 
Luxembourg, Navarra 
(Spain), Norway, 
Portugal 

Belgium, Denmark, 
Luxembourg, Navarra 
(Spain), Norway, 
Portugal, the 
Netherlands 

Belgium, Denmark, 
Luxembourg, Navarra 
(Spain), Norway, 
Portugal, the 
Netherlands, Italy 

Belgium, Denmark, 
Navarra (Spain), 
Norway, Portugal, the 
Netherlands, Italy 

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TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Background 

In late 2019, a novel severe acute respiratory syndrome virus (SARS-CoV-2), causing COVID-19 disease, 
emerged. Since 31 December 2019, and as of 14 June 2023, 276 489 556 cases of COVID-19 (in accordance 
with the applied case definitions and testing strategies in the affected countries) have been reported in the World 
Health Organization Europe Region (WHO Euro), including 2 955 770 deaths [3].  

As of July 2023, eight vaccine products were granted marketing authorisation in the EU/EEA by the European 
Medicines Agency (EMA). Seven vaccines are spike protein-based: Comirnaty (BNT162b2), Spikevax  
(mRNA-1273), Vaxzevria (AZD1222), Jcovden (Ad26.COV 2.5,), Nuvaxovid (NVX-CoV2373), VidPrevtyn Beta 
(J07BX03) and Bimervax (J07BN); and one, Valneva (VLA2001), is a non-spike protein-based vaccine 
(inactivated, adjuvanted). In addition, four adapted mRNA vaccines targeting Omicron subvariants were 
authorised (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). Administration of adapted vaccines 
started in September 2022 onwards as a second and/or third booster vaccination [4,5].  

ECDC is leading activities and studies in the scope of vaccine effectiveness (VE) as part of its now extended 
mandate on monitoring vaccines and vaccination programmes in the post-authorisation phase [6–8]. Some of 
these activities are being implemented as part of the Vaccine Monitoring Platform (VMP), a joint initiative of 
ECDC and EMA for strengthening the continuous monitoring of the safety and effectiveness of vaccines. The 
VEBIS project is being funded as part of the activities undertaken in the VMP. It encompasses various 
effectiveness studies implemented in different settings and populations and using different data sources: VE of 
COVID-19 and influenza vaccines against severe acute respiratory infections in hospital settings, VE of COVID-19 
and influenza vaccines against mild diseases in primary care settings and VE of COVID-19 vaccines in healthcare 
workers (cohort study).  

The current study aimed to monitor VE of COVID-19 vaccines using routinely collected vaccination status and 
outcome data from established electronic health records (EHR) databases. Using a common protocol [1], 
participating countries provide estimates of VE monthly, which are then pooled together using random-effects 
meta-analysis techniques. A proof of concept and a preliminary pilot study were carried out between October 
2021 and April 2022, with the participation of Denmark, Navarra (Spain), Norway, and Portugal. Between April 
and November 2022, a prospective monitoring pilot was implemented by the same four study sites with a later 
addition of Belgium and Luxembourg (since July 2022) [2]. Since November 2022, a prospective monitoring has 
been ongoing in the six study sites [1,911], with the further addition of the Netherlands and Italy (Table 1). In 
this report, VE estimates under monitoring during this later monitoring period are presented. Specifically, this 
includes estimates of rVE of booster doses (relative VE compared to individuals with complete primary 
vaccination ≥24 weeks ago who have not received any booster dose) against hospitalisation due to COVID-19 or 
COVID-19-related death in community-dwelling population 50 years of age or older. 

Overall aim 

The overall aim was to monitor real-time performance of COVID-19 vaccines in the resident populations living 
in the community in the European Union/European Economic Area (EU/EEA) in order to inform COVID-19 
vaccine recommendations. 

Objectives 

Principal objective 
To measure rVE of booster doses of COVID-19 vaccine, in resident populations living in the community aged ≥50 
years in EU/EEA countries, against the following outcomes: 

• 
• 

Hospital admission due to COVID-19; 
Death related to COVID-19.  

The  rVE  of  first,  second  or  third  booster  dose  was  estimated  compared  to  individuals  with  COVID-19  primary 
vaccination administered ≥ 24 weeks ago without a subsequent booster.  

Secondary objective 
To measure COVID-19 rVE by time since the first, second, or third booster dose defined as the number of weeks 
between time of analysis and the date of the last booster dose administered. 

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COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Methodology 

Study design 
This was a retrospective cohort study using data collected routinely in EHR databases. Comparison of the risk of 
severe outcomes (hospitalisation due to COVID-19 and COVID-19-related death) was carried out between 
individuals with different vaccination status. 

Study setting 
The study was carried out in eight EU/EEA countries: Belgium, Denmark, Italy, Luxembourg, Spain (Navarra), the 
Netherlands, Norway, and Portugal, representing close to 51 million people aged ≥50 years. COVID-19 
epidemiology and roll-out of COVID-19 vaccines have been heterogeneous across the eight countries (Table 2).  

Figure 1. Countries participating in the VEBIS multi-country VE study based on EHR 

Table 2. Uptake (%) of complete vaccination with the primary series of COVID-19 vaccine*, first, 
second** and third booster dose in participating EU/EEA countries, as of week 39, 2023  

Country 

Belgium  

Denmark  

Italy 

Luxembourg  

The Netherlands 

Norway  

Portugal  

Spain  

Median EU/EEA  

≥60 years 

98.2/92.6/71.0/14.6 

100.0/98.1/87/2.5 

94/93.1/31.6/2.8 

91.2/85.4/49.5/0.7 

90.3/85.7/55.9/47 

97.5/92.9/61***/12.4 

99.0/98.8/75.4/14.1 

96.7/92.9/61.6/0.4 

91.2/84.9/35.6/4 

Source: ECDC Vaccine Tracker, age groups reflecting the ones reported in this data source [4]. *Full vaccination with the 
primary series of COVID-19 vaccine is defined according to the manufacturer’s instructions for each vaccine product. ** Second 
booster not recommended in this age group as of week 23, 2023. *** Only recommended in those ≥65 years.  

Data sources 

Routinely collected data in various population health registries at national or regional level were used. Table 3 
gives an overview of the data sources used in each eight study sites for the identification of outcome variables 
and vaccination status. The full list of data sources used in the study is provided in Annex 1.

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TECHNICAL REPORT                                                                       COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 3. Information systems based on electronic health records of each participant site  

Study 
variable 

Belgium 

Denmark 

Italy 

Luxembourg 

The Netherlands 

Norway 

Portugal 

Navarra (Spain) 

Study site 

Hospital 
admission due 
to COVID-19 

Clinical Hospital 
Survey database 

Danish National 
Patient Register 
(DNPR) 

National 
Integrated COVID-
19 Surveillance 
Databases 

Epidemiological 
national surveillance 
platform (MSINF) to 
collect daily data from 
hospitals 

National Intensive 
Care Evaluation 
(NICE) COVID-19 
database 

Norwegian Intensive 
Care and Pandemic 
Registry (NIPaR) 

National Hospital 
Discharge database 
(BIMH) 

Enhanced COVID-19 
surveillance with 
individual revision of 
events 

COVID-19-
related death 

Not available 

MiBA and 
Danish Civil 
Registration 
system (CPR) 

National 
Integrated COVID-
19 Surveillance 
Databases 

MSINF + death 
certificate for death 
happened outside 
hospital or nursing 
home 

Not available in 
near real-time 

Norwegian Death 
Registry (DÅR) 

National Death Registry 
(SICO) and National 
Health Service User 
database (NHSU): a cause 
of death is from SICO, 
death status and date of 
death from NHSU. 

Administrative 
database of deaths 
and individual 
revision of events 

Vaccination 
status 

National vaccine 
registry 
(VACCINNET) 

Danish 
Vaccination 
Registry (DVR) 

National 
Vaccination 
Registry 

MSVAC: National 
vaccination registry 

COVID-vaccination 
Information and 
Monitoring System 
(CIMS) 

The National 
Immunisation 
Register (SYSVAK) 

The National Vaccination 
Register (VACINAS) 

Vaccination register 

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TECHNICAL REPORT 

    COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Study period 
RVE estimates were produced each month between July 2022 and September 2023. Study periods covered an 
eight-week follow-up time to allow sufficient numbers of events for estimations, as well as to be sensitive and 
reactive to changes in rVE over time. Each month the eight-week follow-up time is shifted forward by one month. 
A minimum of one month between the end of the study period and data extraction was applied for data 
consolidation. The study observation period presented in this report runs from April 2022 to July 2023.  

Study population 
The study population included individuals in the national vaccination plan and/or the reference population 
registries fulfilling the following criteria during each eight-week study periods: 

• 
• 
• 
• 

• 
• 

Resident in any of the participating EU/EEA countries at the beginning of each study period. 
Aged between 50 and 110 years at the beginning of each study period. 
Not living in a nursing home (if available, and according to last data update). 
First vaccine dose received at a time when it was recommended for the corresponding age group (i.e. 
excluding individuals vaccinated before starting period of recommendation was in place for a target age 
group or, alternatively, for those countries with no clearly defined recommended start date by age, 
excluding the first 5% of persons vaccinated within each age group – for each five-year age category – as 
these first vaccinees may not be representative of their corresponding age group). 
Completed primary COVID-19 vaccination series ≥24 weeks ago. 
Did not have inconsistent or missing data on vaccination (vaccination status unknown, any vaccination 
date unknown, any vaccine brand unknown, number of doses unknown, interval between first and second 
dose shorter than 19 days, interval between complete vaccination and booster dose or between booster 
doses shorter than 90 days, number of doses higher than recommended, received any vaccine brand not 
approved by EMA, or the combination of vaccine brands not resulting in a schedule recommended by 
national public health authorities. 

Definitions  

Vaccination status 

The following definitions were applied: 

• 

• 

• 

• 

Complete COVID-19 vaccination with primary series: individuals who received the primary series of COVID-
19 vaccine doses defined as one dose of Ad26.COV2.S (Jcovden) vaccine or two doses of ChAdOx1-S 
(Oxford/Astra Zeneca), BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), or a combination of any of 
the three vaccines. The two doses should have been administered ≥19 days apart. Individuals became 
eligible for the study ≥24 weeks after complete COVID-19 vaccination with primary series. 
Complete COVID-19 vaccination with first booster dose: individuals who received an additional dose of an EMA-
approved vaccine at least three months (90 days) after completion of primary series (as defined above). This 
status is achieved 14 days after the date of administration of the booster dose (induction period). 
Complete COVID-19 vaccination with second booster dose: individuals who received an additional dose of an 
EMA-approved vaccine at least three months (90 days) after the first booster dose (as defined above). This 
status is achieved 14 days after the date of administration of the booster dose (induction period). 
Complete COVID-19 vaccination with third booster dose: individuals who received an additional dose of an 
EMA-approved vaccine at least three months (90 days) after the second booster dose (as defined above). 
This status is achieved 14 days after the date of administration of the booster dose (induction period). 

Individuals who received a booster dose <14 days ago were analysed separately (i.e. not merged with the 
previous nor the subsequent vaccination status) and rVE was not estimated for this group. 

Time since booster dose vaccination    
Assessment of time since vaccination started at the end of the induction period, i.e. day 14 after the date of 
administration of the last dose (time 0). 

Time since vaccination was classified into three categories as follows: 

• 
• 
• 

<12 weeks (time 0 up to ≤84 days after time 0); 
≥12 weeks & <24 weeks (85 to 168 days, after time 0); 
≥24 weeks (≥169 days, after time 0).  

Time since vaccination was calculated at each point in time by constructing a time-dependent variable.  

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COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Reference groups for rVE estimation 
The rVE of each first, second, and third booster dose (overall and by time since vaccination) was estimated 
compared to receiving complete primary vaccination administered at least 24 weeks ago and without a booster. 

Outcomes 

Outcomes of interest were defined as: 

• 

• 

• 
• 
• 

Hospital admission due to COVID-19: 
− 

Admission to hospital in which COVID-19 is the main diagnosis in the admission or discharge 
record (for example, based on International Classification of Diseases (ICD) coding or similar); 
OR 
Admission to hospital in which admission criteria are compatible with SARI (based on similar 
criteria as in SARI surveillance, ICD coding or similar) AND with a laboratory-confirmed  
SARS-CoV-2 infection ≤14 days before admission or up to 24 hours after admission. 

COVID-19-related death:  
− 

death for which COVID-19 is recorded as the cause of death; 
OR, if the cause of death is not available,  
death with laboratory-confirmed SARS-CoV-2 infection in the previous 30 days after the positive test. 

− 

− 

For each outcome, the censoring date of outcome occurrence (date of the event of interest) was the earliest 
among the date of hospital admission or death, and the date of the laboratory diagnosis (i.e. the date of the first 
diagnosis of the infection episode that resulted in hospital admission or death).  

Confounder  

Basic models were adjusted for age (in five-year categories) and sex and, when appropriate, some geographical 
division within each country. Additionally, estimates were adjusted by previous SARS-CoV-2 infection, 
socioeconomic variables, comorbidities and/or other covariates when available and as appropriate for each study 
site. Since many variables are pre-coded in the established database, the definition for variables and categories 
was heterogeneous across study sites (Annex 2).  

Previous SARS-CoV-2 infection 
Previous infection was classified at the beginning of each study period in two categories: 

• 
• 

No previous infection: No positive SARS-CoV-2 test recorded prior to the first day of the study period. 
Previous infection: At least one positive SARS-CoV-2 test recorded prior to the first day of the study period. 

Demographic and socioeconomic 
• 

Age group, calculated at the beginning of each study based on date of birth. Age was categorised into 
five-year categories to adjust models. Alternatively, some study sites classified age based on year of birth 
(age at the end of the current year). For reporting stratified results by age group the following groups 
were used: 50–64, 65–79 and ≥80 years.  
Sex. 
Socioeconomic status: Income, crowded conditions or others as available in EHR. 
Area level socioeconomic condition (postal code, municipality or other): income per capita, inequality or 
deprivation index 10 or similar, as available in EHR. 

Comorbidities and health-seeking behaviours 
Different variables can be used to document comorbidities. It was recommended to include comorbidities as a 
three-level variable across participating sites: 

• 
• 

• 

No comorbidities related to increased risk of COVID-19. 
Medium risk comorbidities (for example, comorbidities that are associated with the risk of COVID-19 but 
different from immunocompromising conditions, or other classification decided at site level). 
High risk comorbidities (for example, immunocompromising conditions, or other classification decided 
at site level). 

Data analysis 
Vaccination status was a time changing variable defined at the beginning of the eight-week study period. 
Individuals for which vaccination status changed during follow-up period were censored (as free of the event) 
from the vaccination status group they left, and were recorded as a delayed entry into the new vaccination status 
group, on the date their vaccination status changed. 

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COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Individuals were then followed up until the earliest date of: 

• 
• 
• 
• 

Event of interest, with date of the outcome as previously defined; 
Death of any cause (on the date of death); 
Discontinuation in the administrative database (i.e. emigration); 
Administrative censoring (eight weeks after the start of the observation period). 

Cox regression with calendar time as the underlying time scale was used to estimate hazard ratios (HRs) of 
defined outcomes among the group with the vaccine status of interest compared to the reference vaccination 
status group. Relative vaccine effectiveness was defined as rVE = (1-HR) x 100. To estimate the rVE of booster 
doses compared to primary vaccination, we used complete primary vaccination series ≥24 weeks ago without a 
subsequent booster as the reference group. 

Cox regression models were adjusted by age, sex, geographical region (if applicable to the study site), previous 
infection, comorbidities, socioeconomic variables or others as available and relevant at each study site (Annex 2). 

Methods for pooling estimates 

Country-specific HRs and standard errors from each study site were combined in a model using meta-analysis 
techniques. Study sites did not report VE estimates for which the number of events in any of the categories 
being compared was less than five and those were not included in the pooled estimates [11] . Additionally, 
estimates based on less than 15 events after pooling together all participating sites were not reported. A 
random-effects approach using the Paule-Mantel method was used. This acknowledges the possibility that VE can 
differ across the different countries, depending on measured or unmeasured site-specific factors.  

Ethical requirements 
All sites conformed with national and EU ethical and data protection requirements.  

12 

 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Results 

Population characteristics and number of events 
Between April 2022 and July 2023, the number of vaccinated individuals included in the analysis across each 
study period varied widely: between 0.5 to 4.1 million individuals with complete primary vaccination series ≥24 
weeks ago without booster, between 3.1 to 20.9 million individuals completely vaccinated with a first booster, 
between no individual vaccinated to 12.5 million individuals completely vaccinated with a second booster, and 
between no individual vaccinated and 2.7 million completely vaccinated with a third booster. Around 72 900 
hospitalisations due to COVID-19 and 14 300 COVID-19-related deaths were recorded across the different sites 
throughout the study period. 

At the beginning of the study period, most of the study population had received a first booster dose, while the 
proportion of individuals completely vaccinated with primary doses without a booster was very low, especially in 
≥65-year-olds (Figure 2). A second booster was administered first in the spring of 2022 in those aged ≥80 years in 
Belgium, Italy, Luxembourg, and Portugal and in those aged ≥60 years in the Netherlands. This group was followed 
by 65–79-year-olds in the summer (Italy) or the autumn (Belgium and Portugal) of 2022, or by a recommendation 
for all ages (the Netherlands). The third booster dose was then deployed in October–November 2022 for ≥80-year-
olds in the four countries, and in the group 65–79 years in Italy and the Netherlands. In the rest of the countries 
contributing to this study, the second booster was recommended initially in ≥65-year-olds from July 2022 onwards in 
Norway, with the roll-out starting with the oldest age groups, and in ≥80-year-olds from September (Denmark) or 
October (Navarra, Spain) 2022 onwards. Later, Norway recommended a third booster in ≥75-year-olds in March 
2023, while Denmark and Spain have only included this recommendation for ≥80-year-olds in the autumn of 2023. 
Most countries have also recommended booster doses for specific groups at increased risk of severe outcomes, 
outside of the targeted age groups at each point in time. 

The specific number of individuals, person-months contributed to the study and number of hospitalisation events 
per study period, age group and vaccination status are provided in Tables 4, 5, and 6. The corresponding figures 
and tables for the mortality outcome are provided in Annex 3.  

Figure 2. Distribution (%) of study participants’ vaccination status by number of booster doses 
received for each eight-week study period and by age group, April 2022 to July 2023 

13 

 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Table 4. Number of individuals, number of hospitalisations due to COVID-19, and person-months 
across each eight-week period in ≥80-year-olds, April 2022 to July 2023 

Primary vaccination  
≥24 weeks ago without 
a booster  

Primary vaccination 
+ fist booster dose 

Primary vaccination 
+ two booster doses 

Primary vaccination 
+ three booster doses 

Events/ 
person-
month 

177/ 
95 455 

198/ 
102 147 

167/ 
100 502 

117/ 
82 641 

98/ 
158 606 

89/ 
145 605 

93/ 
132 085 

200/ 
146 444 

876/ 
836 935 

462/ 
836 927 

355/ 
833 012 

383/ 
832 028 

302/ 
831 339 

137/ 
825 216 

79/ 
829 390 

N 

1 016 780 

1 030 897 

882 438 

1 173 513 

1 091 489 

983 180 

718 850 

427 355 

2 333 019 

2 256 514 

2 197 866 

2 186 666 

2 182 943 

2 072 663 

2 076 542 

Events/ 
person-
month 

1 762/ 
1 843 384 

1 618/ 
1 634 301 

1 578/ 
1 275 533 

2 052/ 
2 018 185 

1 178/ 
1 847 555 

833/ 
1 353 738 

522/ 
852 138 

764/ 
653 291 

5 440/ 
4 081 593 

2 841/ 
4 029 290 

2 158/ 
3 982 995 

2 212/ 
3 977 836 

1 756/ 
3 974 305 

847/ 
3 769 324 

419/ 
3 780 071 

N 

0 

0 

341 905 

866 535 

1 252 549 

1 542 721 

1 176 467 

1 026 198 

2 550 422 

2 582 067 

2 535 418 

2 517 378 

2 493 103 

1 982 081 

2 193 302 

Events/ 
person-month 

<5/0 

<5/0 

123/ 
425 531 

584/ 
1 408 781 

454/ 
1 532 594 

478/ 
1 467 698 

446/ 
1 510 236 

1 167/ 
1 697 867 

5 009/ 
4 375 521 

2 761/ 
4 586 400 

2 579/ 
4 584 882 

2 864/ 
4 584 096 

2 234/ 
4 520 088 

941/ 
3 559 457 

490/ 
3 996 201 

N 

– 

– 

– 

– 

– 

– 

607 488 

927 661 

1 114 830 

1 173 244 

1 185 525 

1 185 721 

1 227 272 

984 723 

965 713 

Events/ 
person-month 

– 

– 

– 

– 

– 

– 

168/ 
862 762 

648/ 
1 600 878 

1 016/ 
1 902 532 

1 016/ 
2 078 505 

1 450/ 
2 132 358 

1 305/ 
2 152 304 

697/ 
2 188 324 

322/ 
1 766 726 

179/ 
1 748 257 

Study 
period 

Apr to May 
2022 

May to Jun 
22 

Jun to Jul 
2022 

Jul to Aug 
2022 

Aug to Sep 
2022 

Sep to Oct 
22 

Oct to Nov 
2022 

Nov to Dec 
2022 

N 

58 016 

65 186 

63 274 

90 479 

89 173 

86 627 

76 420 

83 704 

Dec 2022 to 
Jan 2023 

465 170 

Jan to Feb 
2023 

Feb to Mar 
2023 

Mar to Apr 
2023 

Apr to May 
2023 

May to Jun 
2023 

Jun to Jul 
2023 

462 487 

459 347 

458 333 

457 664 

454 035 

456 016 

14 

 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 5. Number of individuals, number of hospitalisations due to COVID-19, and person-months 
across each eight-week period in 65–79 years, April 2022–July 2023 

Primary vaccination ≥24 
weeks ago without a 
booster  

Primary vaccination 
+ first booster dose 

Primary vaccination 
+ two booster doses 

Primary vaccination 
+ three booster doses 

N 

141 891 

179 002 

195 234 

294 656 

295 807 

294 073 

281 165 

336 699 

1 116 297 

1 117 472 

1 112 174 

1 116 291 

1 118 440 

1 107 982 

1 108 402 

Events/ 
person-
month 

115/ 
230 175 

110/ 
269 620 

99/ 
309 256 

153/ 
522 712 

102/ 
538 691 

73/ 
510 312 

75/ 
460 744 

250/ 
574 012 

747/ 
2 015 488 

476/ 
2 031 916 

399/ 
2 030 489 

368/ 
2 039 725 

255/ 
2 043 974 

128/ 
2 025 876 

61/ 
2 027 847 

N 

2 723 031 

2 739 833 

2 698 656 

5 028 270 

4 897 957 

4 701 721 

3 323 770 

1 911 093 

6 860 521 

6 587 984 

6 429 926 

6 402 563 

6 373 563 

6 283 390 

5 974 550 

Events/ 
person-
month 

920/ 
4 971 604 

511/ 
3 074 645 

1 282/ 
4 935 561 

1 938/ 
8 989 085 

1 153/ 
8 806 671 

919/ 
6 742 351 

524/ 
3 752 227 

754/ 
2 742 833 

4 213/ 
1 2026 519 

2 297/ 
11 801 443 

1 969/ 
11 704 199 

1 889/ 
11 703 573 

1 515/ 
11 665 286 

799/ 
11 499 953 

327/ 
10 929 614 

N 

- 

- 

- 

64 628 

260 009 

414 516 

3 550 638 

4 024 273 

6 318 413 

6 417 000 

6 364 831 

6 348 105 

6 266 592 

5 461 271 

4 315 180 

Events/ 
person-month 

N 

Events/ 
person-month 

- 

- 

- 

72/ 
50 411 

68/ 
195 897 

71/ 
528 062 

214/ 
4599274 

998/ 
6 643 666 

2 720/ 
11 025 786 

1 687/ 
11 479 756 

1 752/ 
11 609 407 

1 863/ 
11 641 729 

1 420/ 
11 476 071 

602/ 
9 960 057 

295/ 
7 881 074 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

1 202 681 

1 353 163 

1 408 441 

1 422 228 

1 426 943 

1 424 150 

1 423 789 

1 365 863 

375/ 
1 995 982 

547/ 
2 304 388 

534/ 
2 457 090 

781/ 
2 539 261 

697/ 
2 567 173 

335/ 
2 569 717 

152/ 
2 571 486 

64/ 
2 469 075 

Study 
period 

Apr 22 to 
May 22 

May 22 
to Jun 22 

Jun 22 to 
Jul 22 

Jul 22 to 
Aug 22 

Aug 22 
to Sep 
22 

Sep 22 
to Oct 22 

Oct 22 to 
Nov 22 

Nov 22 
to Dec 
22 

Dec 22 
to Jan 23 

Jan 23 to 
Feb 23 

Feb 23 to 
Mar 23 

Mar 23 to 
Apr 23 

Apr 23 to 
May 23 

May 23 
to Jun 23 

Jun 23 to 
Jul 23 

15 

 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Table 6. Number of individuals, number of hospitalisations due to COVID-19 (events), and person-
months in 50–64 years across each eight-week study period, April 2022–July 2023  

Study 
period 

Apr to 
May 2022 

May to 
Jun 2022 

Jun to Jul 
2022 

Jul to Aug 
2022 

Aug to 
Sep 2022 

Sep to Oct 
2022 

Oct to Nov 
2022 

Nov to 
Dec 2022 

Dec 2022 
to Jan 
2023 

Jan to Feb 
2023 

Feb to 
Mar 2023 

Mar to Apr 
2023 

Apr to 
May 2023 

May to 
Jun 2023 

Jun to Jul 
2023 

Primary vaccination ≥24 weeks 
ago without a booster 

Primary vaccination 
+ first booster dose 

Primary vaccination 
+ two booster doses 

N 

Events/ 
person-month 

349 395 

368 291 

384 505 

974 768 

970 151 

966 106 

961 917 

689 169 

2 535 595 

2 524 998 

2 500 939 

2 494 101 

2 516 701 

2 463 493 

2 471 549 

23/ 
602 279 

25/ 
626 713 

35/ 
651 450 

74/ 
1 711 719 

54/ 
1 774 164 

42/ 
1 753 990 

30/ 
1 739 865 

65/ 
1 205 770 

360/ 
4 584 567 

206/ 
4 618 834 

165/ 
4 584 383 

164/ 
4 576 502 

138/ 
4 619 306 

70/ 
4 520 223 

35/ 
4 536 536 

N 

2 193 694 

2 201 324 

2 207 773 

7 072 855 

6 156 025 

6 159 876 

5 563 895 

3 293 661 

11 681 499 

10 575 239 

11 021 285 

10 957 328 

10 966 215 

9 927 882 

9 938 765 

Events/ 
person-month 

153/ 
4 007 754 

96/ 
4 032 618 

246/ 
4 038 609 

480/ 
11 352 815 

312/ 
11 180 657 

276/ 
10 516 016 

189/ 
8 485 806 

207/ 
5 226 832 

1575/ 
20 626 765 

886/ 
19 221 185 

727/ 
20 174 161 

705/ 
20 095 261 

612/ 
20 126 473 

354/ 
18 190 417 

166/ 
18 214 102 

N 

- 

- 

- 

- 

- 

- 

2 130 793 

2 463 925 

3 608 723 

3 477 150 

3 587 431 

3 581 200 

3 455 344 

2 796 317 

1 721 060 

Events/ 
person-month 

- 

- 

- 

- 

- 

- 

26/ 
2 418 882 

137/ 
3 662 514 

387/ 
6 081 053 

229/ 
5 995 826 

252/ 
6 578 466 

246/ 
6 600 424 

191/ 
6 383 611 

88/ 
5 156 777 

37/ 
3 152 996 

Due to the timing of booster vaccination roll-out differing across participating countries, the relative contribution of each study 
site differed by vaccination status (Figure 3). For example, third booster rVE estimates were only based on data from the 
Netherlands and Italy in the group 65 to 79 years, plus Belgium and Portugal for the group ≥80 years. 

16 

 
 
 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Figure 3. Distribution of cumulative person-months (%) for each study site by age group and by 
number of booster doses administrated and by country, April 2022* to July 2023 

A description of the characteristics of the study population was only available from November 2022 onwards 
(month where these descriptive data had to be reported by all participating countries). As the number of 
vaccine doses increased so did the share of individuals with medium and high-risk comorbidities, in 
accordance with the preferential vaccination of these groups (Annex 4). A series of figures in Annex 4 
show the cumulative proportion of person-months throughout the study period by vaccine product according to 
the vaccination status at the time of the study. Pfizer vaccine products were the most administered for primary 
vaccination doses, followed by AstraZeneca and Moderna products. First booster doses were monovalent 
(Wuhan-based) Pfizer and Moderna vaccines, with a negligible proportion of bivalent Pfizer vaccines (both BA.1 
and BA.4/5) in those with final vaccination status of first booster, showing late first booster administrations in the 
autumn of 2022. Various products were administered as second booster dose including monovalent (spring 2022) 
and bivalent (including Wuhan and Omicron BA.1 or BA.4/5 mRNA) products (autumn 2022). Interestingly, for 
those contributing to the study within the third booster group, all had been vaccinated with a monovalent vaccine 
as a second booster, which is consistent with second booster vaccination in the spring of 2022, before bivalent 
vaccines became available, and third booster vaccination later on, in the autumn of 2022. For the group 
contributing to the study as second booster group, there is a mix of monovalent and bivalent products, showing 
the mix of individuals vaccinated in the spring and autumn campaigns, before and after the bivalent vaccines 
became available, respectively. Finally, third booster doses were almost exclusively bivalent vaccines, more 
frequently BA.1 than BA.4/5. 

17 

 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Relative vaccine effectiveness of first, second and third 
booster against hospitalisation due to COVID-19 

First booster 

Between April 2022 and July 2023, the rVE of the first booster fluctuated, from about 50% to lower values in all 
age groups (Tables 7-9; Figure 4, green symbols) with rVE declining over calendar time (Figure 5). The rVE of a 
first booster within the first 12 weeks after administration was >50%. It then dropped ≥12 weeks after its 
administration, and dropped even more at ≥24 weeks. Between June 2022 and July 2023, a first booster showed 
little to no added protection at least 24 weeks after its administration compared to complete primary vaccination 
only, with rVE reaching down to 15% (95% CI: -38; 48) in ≥80-year-olds, 27% (95% CI: 4; 44) in 65–79-year-
olds, and 6% (95% CI: -38; 36) in 50–64-year-olds at the end of the study period. Sporadic rVE estimates for a 
first booster <12 weeks during 2023 correspond to few people vaccinated late with a first booster and are 
difficult to interpret. 

Second booster 
The rVE of a second booster (compared to complete primary vaccination ≥24 weeks ago with no booster) was high 
shortly after administration, reaching 72% (95% CI: 62; 80) in ≥80-year-olds and 76% (95% CI: 68; 82) in 65–79-
year-olds, in November–December 2022 and 55% (95% CI: 37; 67) in 50–64-year-olds in January–February 2023. 
In ≥80-year-olds, the highest rVE estimates were observed in spring 2022 and autumn 2022 corresponding to a 
more extensive deployment of the vaccine in Belgium and Portugal (spring 2022 campaign) and then in other 
participating countries (autumn 2022 campaign). The rVE declined with time since booster vaccination (Figure 5), 
with rVE estimates of <50% at ≥24 weeks after administration. In the last period available (June–July 2023), the 
rVE of the second booster administered ≥24 weeks ago was 16% (95% CI: -26; 44) in ≥80-year-olds, 31% (95% 
CI: 3; 50) in 65–79-year-olds and -36% (95% CI: -133; 20) in those aged 50–64 years. 

Third booster  

The rVE of a third booster administered during autumn 2022 could only be estimated in those groups who 
received the second booster vaccination during the spring 2022 campaign in Belgium, Italy, Portugal, and the 
Netherlands, following the roll-out of the campaign in each country. The rVE of the third booster (compared to 
complete primary vaccination ≥24 weeks ago with no booster) in October–November 2022 reached 72% (95% 
CI: 61; 80) in ≥80-year-olds, compared to complete primary vaccination only, similar to the rVE of a second 
booster administered simultaneously in the remaining study sites during the autumn 2022 campaign (Figure 4). 
The rVE of third boosters waned rapidly, being low or null beyond 12 weeks of administration (Figure 5). In the 
last period available (June–July 2023), the rVE of the third booster administered ≥24 weeks ago was 16% (95% 
CI: -42; 50) in ≥80-year-olds and 6% (95% CI: -71; 49) in 65–79-year-olds. Third booster doses were not 
recommended in 50–64-year-olds during the observation period for this analysis. 

Sensitivity analysis 

An alternative analysis was performed, restricting to the six sites that have contributed during most of the study 
period (Annex 5). Most of the results and conclusions remain unchanged. The most notable difference is that a 
moderate protection against hospitalisation was estimated for the second booster ≥24 weeks ago in the group 
aged ≥80 years by June–July 2023. 

18 

 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Figure 4. Relative* vaccine effectiveness (95% confidence intervals) against hospitalisation due to 
COVID-19 of first, second and third booster dose between April 2022 and July 2023  

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without 
booster administered ≥24 weeks ago. 

19 

 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Figure 5. Relative* vaccine effectiveness (95% confidence intervals) against hospitalisation due to 
COVID-19 of the first, second and third booster dose by time since the booster between April 2022 
and July 2023  

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without 
booster administered ≥24 weeks ago. 

20 

 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 7. Relative* vaccine effectiveness (95% confidence intervals) in those aged ≥80 years against hospitalisation due to COVID-19 of the first, second and 
third booster dose between April 2022 and July 2023 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

April 1 to May 26 2022 

52.2% 
(24.7; 69.6) 

54.7% 
(37.2; 67.3) 

54.6% 
(34.4; 68.5) 

47.8% 
(36.8; 56.9) 

May 1 to June 25 2022 

June 1 to July 26 2022 

42.2% 
(32.6; 50.5) 

72.0% 
(55.7; 82.3) 

41.4% 
(29.9; 51.1) 

39.3% 
(29.4; 47.8) 

- 

- 

- 

- 

44.1% 
(29.4; 55.7) 

- 

24.9% 
(-53.2; 63.1) 

41.8% 
(25.2; 54.7) 

71.0% 
(61.4; 78.2) 

71.0% 
(61.4; 78.2) 

July 1 to August 25 
2022 

37.5% 
(16; 53.5) 

70.0% 
(46.5; 83.2) 

28.3% 
(-2.9; 50.1) 

36.5% 
(14.6; 52.8) 

57.8% 
(48.2; 65.6) 

62.5% 
(52.7; 70.2) 

- 

- 

- 

27.8% 
(10.4; 41.9) 

57.2% 
(43.1; 67.9) 

60.2% 
(45; 71.3) 

29.9% 
(11.7; 44.3) 

50.7% (35.8; 62. 
2) 

60.2% 
(46.9; 70.2) 

30.0% 
(-7.4; 54.3) 

41.8% 
(26.6; 53.9) 

68.4% 
(54.5; 78.1) 

75.6% 
(65.5; 82.8) 

38.7% 
(17.9; 54.2) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

72.1% 
(60.6; 80.2) 

70.8% 
(60.2; 78.6) 

- 

- 

- 

- 

- 

- 

- 

- 

47.2%  
(8.9; 69.4) 

26.4%  
(13.5; 37.3) 

65.9%  
(49.1; 77.2) 

72.1%  
(62.1; 79.5) 

49.2%  
(31.9; 62.1) 

20.9%  
(-100.5; 68.8) 

62.4%  
(53.7; 69.4) 

61.8%  
(53; 69) 

22.1% 
 (-5.1; 42.4) 

-38.6%  
(-103.7; 5.7) 

14.4%  
(-502.1; 87.8) 

14.0% 
 (-10.2; 32.9) 

52.8% 
 (29.1; 68.6) 

57.6%  
(35.1; 72.3) 

47.0%  
(17.5; 66) 

16.8%  
(-48.8; 53.4) 

47.3% 
 (25.7; 62.6) 

47.7%  
(25.7; 63.2) 

53.0%  
(38.4; 64.2) 

-79.4%  
(-178.9; -15.4) 

9.0%  
(-23.5; 32.9) 

40.6% 
 (15.6; 58.2) 

48.2% 
 (24.1; 64.6) 

47.9%  
(5.1; 71.4) 

12.2% 
 (-29.3; 40.4) 

30.0% 
 (2.4; 49.8) 

44.5%  
(13; 64.7) 

16.2% 
 (-39.2; 49.5) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

August 1 to September 
25 2022 

September 1 to October 
26 2022 

October 1 to November 
25 2022 

November 1 to 
December 26 2022 

December 1 2022 to 
January 25 2023 

January 1 to February 
25 2023 

February 1 to March 28 
2023 

March 1 to April 25 2023 

April 1 to May 26 2023 

28.9% 
(11.8; 42.7) 

32.2% 
(14.9; 46) 

45.5% 
(31.4; 56.7) 

31.6%  
(19.5; 41.9) 

- 

- 

- 

- 

17.4%  
(-17.3; 41.9) 

-4.8%  
(-35.1; 18.7) 

11.9% 
 (-25.1; 38) 

13.1%  
(-28.6; 41.3) 

- 

- 

- 

- 

- 

-8.0% 
 (-42.4; 18.2) 

21.6% 
 (-11; 44.6) 

10.7%  
(-11.7; 28.6) 

28.8%  
(-2; 50.2) 

-2.5%  
(-55.4; 32.4) 

7.5%  
(-70.8; 49.9) 

40.1%  
(-45.1; 75.3) 

3.5%  
(-76.9; 47.4) 

-81.7%  
(-206.1; -7.8) 

10.9%  
(-27; 37.5) 

25.0%  
(-15.5; 51.3) 

19.1% 
 (-8.1; 39.4) 

32.9%  
(4.6; 52.8) 

1.2%  
( 
-52.8; 36.2) 

5.0%  
(-93.4; 53.4) 

31.4% 
 (-80.9; 74) 

-1042.7%  
(-Inf; 94.8) 

48.2% 
 (14; 68.8) 

8.8%  
(-153.2; 67.1) 

-165.8% 
 (-341.8; -59.9) 

11.3% 
 (-30.8; 39.9) 

27.8% 
 (-12.2; 53.5) 

- 

36.4%  
(4.4; 57.7) 

26.3% 
(-16.8; 53.4) 

24.2%  
(-45.8; 60.6) 

56.2% 
 (-64; 88.3) 

-0.8%  
(-42.2; 28.5) 

1.5% 
 (-67.3; 42.1) 

21 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

May 1 to June 25 2023 

June 1 to July 26 2023 

18.3%  
(-52.3; 56.1) 

14.9% 
 (-38.1; 47.6) 

- 

- 

- 

- 

17.6%  
(-53.4; 55.7) 

16.6% 
 (-34.8; 48.4) 

14.8%  
(-38.4; 47.6) 

17.4%  
(-23.9; 44.9) 

- 

- 

-16.4%  
(-57.5; 14) 

14.4%  
(-38.7; 47.2) 

36.6% 
 (-67.9; 76) 

60.2%  
(-237.3; 95.3) 

-69.3%  
(-319.2; 31.6) 

- 

16.0% 
 (-26.2; 44 

33.9%  
(-39; 68.6) 

- 

- 

>24 weeks 

-8.1%  
(-76.6; 33.9) 

15.8%  
(-41.8; 50) 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago. 

22 

   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 8. Relative* vaccine effectiveness (95% confidence intervals) in those aged 65–79 years against hospitalisation due to COVID-19 of the first, second 
and third booster dose between April 2022 and July 2023 

Study period 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

April 1 to May 26 2022 

64.2%  

49.7%  

65.2%  

40.7%  

(42.2; 77.8) 

(18.7; 68.8) 

(42.7; 78.9) 

(-98.3; 82.3) 

May 1 to June 25 2022 

47.1%  

(33.6; 57.8) 

June 1 to July 26 2022 

34.6%  

July 1 to August 25 
2022 

August 1 to September 
25 2022 

September 1 to 
October 26 2022 

October 1 to November 
25 2022 

(19.2; 47) 

47.5%  

(30.6; 60.3) 

43.2%  

(20.6; 59.3) 

18.6%  

(-8.1; 38.7) 

30.4%  

(9.8; 46.3) 

November 1 to 
December 26 2022 

43.5%  

(31.1; 53.7) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

47.7%  

47.6%  

(25.5; 63.3) 

(34.1; 58.4) 

20.5%  

36.0% 

(-4.5; 39.6) 

 (20.9; 48.3) 

12.9%  

48.5%  

-16.1; 34.6) 

(31.6; 61.3) 

- 

- 

- 

- 

- 

- 

- 

- 

43.9%  

(21.3; 59.9) 

18.4%  

(-7.2; 37.8) 

22.7%  

(-29.6; 53.9) 

51.2% 

(9.9; 73.6) 

75.1%  

68.4%  

(42.5; 82.6) 

65.1% 

 (34.3; 81.5) 

27.8% (6.3; 44.4) 

(65.8; 81.8) 

76.6% (66.5; 83.6) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

38.0% (20.3; 51.8) 

75.4% (60.1; 84.8) 

75.7% (68.1; 81.5) 

73.4%  

14.0%  

64.6%  

64.6%  

(20.8; 91.1) 

(-21.7; 39.2) 

(53; 73.4) 

(52.9; 73.3) 

- 

- 

- 

- 

- 

- 

- 

- 

December 1 2022 to 
January 25 2023 

40.1%  

24.2%  

-3.3% 

(21; 54.5) 

(-14.7; 49.9) 

 (-97.3; 45.9) 

34.9%  

(18; 48.3) 

67.4% (46.8; 80.1) 

67.1% (52.6; 77.1) 

January 1 to February 
25 2023 

33.7%  

(26.5; 40.3) 

February 1 to March 28 
2023 

22.1% 

 (12.5; 30.7) 

March 1 to April 25 
2023 

April 1 to May 26 2023 

-271.5% 

 (-Inf; 82.8) 

13.7% 

 (0.7; 25) 

- 

- 

- 

- 

8.8% 

 (-32.4; 37.2) 

51.1%  

(23; 68.9) 

8.8% 

15.3% 

 (-119.3; 62.1) 

 (4.4; 24.9) 

- 

13.4%  

(0.4; 24.8) 

33.4% (26.1; 40) 

56.6% (44.5; 66.1) 

62.0% (55.8; 67.4) 

20.2% (10.3; 29) 

39.1% (31.3; 46.1) 

55.6% (44.8; 64.3) 

61.0% 

10.9%  

57.0% 

57.2%  

48.5% 

 (39.1; 75) 

(-76; 54.9) 

 (39.3; 69.5) 

(35.2; 71.7) 

 (20.4; 66.7) 

54.0% 

24.8%  

55.5%  

58.8% 

57.3% 

 (41.3; 63.9) 

(2.2; 42.2) 

(37.1; 68.5) 

 (29.4; 75.9) 

 (42.9; 68.1) 

48.1%  

19.9%  

43.7%  

57.5%  

31.5% 

(40.1; 55.1) 

(7.7; 30.5) 

(21.5; 59.6) 

(19.1; 77.6) 

 (-33.7; 64.9) 

43.1%  

(28; 55.1) 

39.8%  

(17; 56.3) 

55.8% (37.5; 68.8) 

45.7% 

32.8% 

37.5% 

64.7% 

24.8% 

51.3% 

 (36.4; 53.7) 

 (10; 49.8) 

 (0.8; 60.7) 

 (41.3; 78.8) 

 (-59.8; 64.6) 

 (26.3; 67.8) 

52.6% (19.5; 72.1) 

42.1% 

39.1%  

41.5%  

 (23.1; 56.3) 

(12.7; 57.6) 

(0.6; 65.6) 

- 

39.0%  

53.5% 

(-21.8; 69.4) 

 (30.4; 69) 

23 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Study period 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

May 1 to June 25 2023 

11.3% 

 (-7.6; 27) 

June 1 to July 26 2023 

27.1% 

 (4.2; 44.4) 

- 

- 

- 

- 

10.8% 

 (-8.2; 26.6) 

26.8% 

 (4; 44.2) 

21.5% 

 (3.7; 36) 

26.9% 

 (3; 44.9) 

- 

- 

25.9%  

(0.2; 45) 

19.2% 

19.9%  

 (0.6; 34.4) 

(-36.2; 52.8) 

- 

30.6% 

4.1% 

 (3.4; 50.1) 

 (-58.7; 42.1) 

- 

- 

17.5%  

-0.4% 

(-34.7; 49.5) 

 (-167.7; 62.4) 

- 

6.3% 

 (-71.1; 48.7) 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago. 

Table 9. Relative* vaccine effectiveness (95% confidence intervals) in those aged 50-64 years against hospitalisation due to COVID-19 of the first, second 
and third booster dose between April 2022 and March 2023 

Study period 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

April 1 to May 26 2022 

33.8%  

28.6%  

34.2% 

(-36.6; 67.9) 

(-55.9; 67.3) 

 (-54.1; 71.9) 

May 1 to June 25 2022 

June 1 to July 26 2022 

July 1 to August 25 
2022 

August 1 to September 
25 2022 

September 1 to October 
26 2022 

55.6% 

 (27; 73) 

39.5%  

(11.8; 58.5) 

35.4%  

(16.2; 50.2) 

31.0% 

 (-0.8; 52.7) 

15.6%  

(-37.5; 48.2) 

- 

- 

- 

- 

- 

66.6% 

 (62.9; 69.9) 

56.0%  

(29.2; 72.7) 

48.6%  

(20.6; 66.7) 

- 

- 

- 

- 

33.3%  

(-21.3; 63.4) 

32.8%  

(12.5; 48.4) 

28.1%  

(-10.1; 53) 

7.4%  

(-62.7; 47.3) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

24 

   
 
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Study period 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

October 1 to November 
25 2022 

9.4% 

 (-46.9; 44.1) 

November 1 to 
December 26 2022 

December 1 2022 to 
January 25 2023 

January 1 to February 
25 2023 

February 1 to March 28 
2023 

March 1 to April 25 
2023 

April 1 to May 26 2023 

May 1 to June 25 2023 

June 1 to July 26 2023 

44.0%  

(22.1; 59.7) 

38.2%  

(30.4; 45.2) 

33.9%  

(22.6; 43.6) 

31.1%  

(17.8; 42.3) 

31.8%  

(5.8; 50.7) 

28.2%  

(13; 40.7) 

8.4% 

 (-20.1; 30.2) 

6.7% 

 (-36.9; 36.4) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

-39.9% 

 (-122.4; 12.1) 

- 

- 

- 

- 

- 

- 

8.1%  

(-47.3; 42.6) 

40.8%  

(9.8; 61.2) 

38.1%  

(30.2; 45.1) 

32.8%  

(21.3; 42.6) 

31.1%  

(17.7; 42.2) 

30.1%  

(0; 51.1) 

27.7%  

(12.2; 40.5) 

8.2% 

(-20.4; 30) 

6.1% 

 (-37.7; 36) 

61.6% 

 (10.2; 83.6) 

36.3%  

(-40.8; 71.2) 

47.2% 

 (6.2; 70.2) 

54.9%  

(23.2; 73.5) 

24.5% 

 (5.6; 39.6) 

27.7% 

 (9.4; 42.2) 

16.9%  

(-6.5; 35.2) 

-13.0% 

 (-59.7; 20.1) 

-31.6%  

(-122; 21.9) 

- 

32.2%  

(-54.7; 70.3) 

49.0% 

 (2.4; 73.4) 

54.6%  

(36.9; 67.4) 

38.4% 

 (7.7; 58.9) 

- 

- 

- 

- 

- 

- 

30.9%  

(12.1; 45.7) 

41.0% 

(-16; 70) 

33.2%  

(11.1; 49.9) 

42.2% 

 (23.6; 56.3) 

46.9% 

 (-4.3; 73) 

-2.2% 

 (-75.2; 40.3) 

- 

- 

- 

-89.0% 

 (-146.4; -45) 

-38.4%  

(-88.3; -1.8) 

-4.7% 

 (-44.2; 24) 

-10.9%  

(-48.6; 17.2) 

3.2%  

(-44; 35) 

-24.7% 

 (-83.2; 15.1) 

-36.1%  

(-132.5; 20.4) 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago.

25 

 
TECHNICAL REPORT 

        COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Relative vaccine effectiveness of first, second and third 
booster against COVID-19-related death 

First booster  

Between April 2022 and July 2023, the overall rVE of the first booster against COVID-19 related death showed a 
similar range and trend to that of rVE against hospitalisation due to COVID-19, although estimates had high 
uncertainty, particularly in the 50–64-year-olds group (Tables 10, 11, 12, Figures 6, 7).  

Second booster  

The second booster dose substantially restored the protection against COVID-19-related death (Figure 7). The 
overall rVE (compared to complete primary vaccination ≥24 weeks ago with no booster) reached 73% (95% CI: 
38; 88) in ≥80-year-olds in October–November 2022, 83% (95% CI: 68; 91) in 65–79-year-olds November–
December 2022, and 63% (95% CI: 25; 82) in 50–64-year-olds in December 2022–January 2023. rVE was higher 
when restricting to those within the first 12 weeks of second booster administration. 

In the last available period, June–July 2023, the rVE of the second booster administered ≥24 weeks ago 
(compared to complete primary vaccination ≥24 weeks ago with no booster), was -12% (95% CI: -579; 82) in 
≥80-year-olds and 29% (95% CI: -34; 63) in 65–79-year-olds. The observed trend was similar to the one shown 
against hospitalisation. 

Third booster  

The rVE of the third booster dose administered in the autumn 2022 in the population who had received the 
second booster vaccination during spring 2022, could only be consistently estimated against death in ≥80-year-
olds based on data provided by Portugal (even though a third booster was recommended for population 65–79 
years, there were not sufficient events to allow estimation in this group). The rVE of the third booster (compared 
to complete primary vaccination ≥24 weeks ago with no booster) in October–November 2022, administered less 
than <12 weeks after administration, was 62% (95% CI: 45; 74), similar to rVE estimates for the second booster 
administered simultaneously in other study sites (Figure a). The rVE of third boosters waned rapidly thereafter. In 
June–July 2023, the rVE of a third booster administered ≥24 weeks ago (compared to complete primary 
vaccination ≥24 weeks ago with no booster) was -213% (95% CI: -3242; 71), the wide confidence interval 
showing that it was based on a very small number of events, particularly in the reference group of people with 
complete primary vaccination without boosters (≥24 weeks ago). 

Sensitivity analysis 

An alternative analysis was performed, restricting to the six sites that have contributed during most of the study 
period, with no changes in the conclusion (Annex 5). 

26 

 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Figure 6. Relative* vaccine effectiveness (95% confidence intervals) against COVID-19-related 
death of the first, second and third booster dose between April 2022 and July 2023  

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series 
without booster administered ≥24 weeks ago. 

27 

 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update        TECHNICAL REPORT 

Figure 7. Relative* vaccine effectiveness (95% confidence intervals) against COVID-19-related 
death of the first, second and third booster dose by time since the booster between April 2022 and 
July 2023  

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without 
booster administered ≥24 weeks ago. 

28 

 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 10. Relative* vaccine effectiveness (95% confidence intervals) in ≥80 years against COVID-19-related death of the first, second and third booster 
dose between April 2022 and July 2023 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 
weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 
weeks 

>24 weeks 

Study period 

April 1 to May 26 
2022 

May 1 to June 25 
2022 

June 1 to July 26 
2022 

July 1 to August 
25 2022 

August 1 to 
September 25 
2022 

September 1 to 
October 26 2022 

October 1 to 
November 25 
2022 

November 1 to 
December 26 
2022 

45.2% 

(15.5; 64.5) 

37.1% 

(15.2; 53.4) 

34.6% 

(10.7; 52.1) 

34.6%  

(5.8; 54.5) 

December 1 2022 
to January 25 
2023 

January 1 to 
February 25 2023 

February 1 to 
March 28 2023 

March 1 to April 25 
2023 

7.0% (-41; 38 

.7) 

11.0% 

 (-39.8; 43.4) 

-5.7% 

 (-67.8; 33.4) 

-3.3% 

 (-62.2; 34.2) 

- 

- 

- 

- 

- 

- 

- 

- 

61.3% 

65.0% 

62.2% 

53.7% 

(48.3; 71) 

(15.6; 85.5) 

(45.9; 73.6) 

(44.4; 61.5) 

59.2% 

66.0% 

36.5% 

60.3% 

(23.6; 78.2) 

(50.4; 76.7) 

(24.4; 46.6) 

(26.3; 78.6) 

- 

- 

- 

- 

53.1% 

76.0% 

25.2% 

52.9% 

68.0% 

68.0% 

(32.2; 67.5) 

(65.1; 83.5) 

(2.2; 42.8) 

(27.6; 69.3) 

(60.3; 74.2) 

(60; 74.4) 

56.5% 

73.0% 

5.0% 

55.8% 

58.1% 

60.3% 

(32.7; 72) 

(54.2; 84.1) 

(-63; 44.6) 

(29.7; 72.3) 

(44.5; 68.3) 

(41.4; 73.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

44.6% 

59.9% 

62.1% 

(3.9; 68.1) 

(-29.6; 87.6) 

(-25.7; 88.6) 

33.0% 

75.1% 

82.7% 

-18.0% 

(-11.7; 59.8) 

(-109.4; 97) 

(-14.9; 97.4) 

(-74; 20) 

15.9% 

73.3% 

85.0% 

1.0% 

(-18.8; 40.4) 

(38.2; 88.4) 

(76; 90.6) 

(-44.1; 32) 

15.0%  

72.1% 

79.9% 

33.5% 

(-12.8; 35.9) 

 (44.5; 86) 

 (71.7; 85.7) 

 (2.8; 54.6) 

-90.3% 

-3.3% 

51.2%  

56.7% 

36.0% 

-26.8% 

 (-219.1; -13.5) 

 (-61.5; 33.9) 

(3.3; 75.4) 

 (24.1; 75.3) 

 (-44.9; 71.8) 

 (-52; -5.7) 

-2.6% 

51.0% 

43.7%  

39.0%  

-11.8% 

 (-55.3; 32.2) 

 (7.1; 74.1) 

(-23.1; 74.2) 

(-19.7; 69) 

 (-57.9; 20.9) 

-16.2% 

46.3% 

14.0% 

40.1% 

23.1%  

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

64.0% 

62.0% 

(48.1; 75) 

(44.7; 73.9) 

58.0%  

58.0%  

(41.6; 69.8) 

(41.1; 70.1) 

- 

- 

- 

- 

- 

- 

- 

- 

47.4%  

(26; 62.6) 

34.6%  

(8.9; 53) 

-5.5% 

49.1% 

30.0%  

 (31.4; 62.3) 

(-10.7; 55.7) 

37.4% 

37.0% 

 (9.3; 56.8) 

 (0.4; 60.2) 

-20.4%  

-25.2% 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

 (-65.1; 18.2) 

 (-19.5; 75.9) 

 (-88.6; 60.8) 

 (-13.5; 68.4) 

(-131.1; 74.4) 

 (-51.5; 26.5) 

(-120.8; 34.4) 

 (-160.5; 39.8) 

-7.4% 

33.1%  

 (-74.4; 33.9) 

(-47; 69.5) 

- 

41.0% 

7.0% 

12.1% 

-100.4% 

-14.4%  

-99.0% 

 (-9.2; 68.1) 

 (-154; 66) 

 (-56.6; 50.7) 

 (-350.2; 10.8) 

(-338.3; 70.2) 

 (-364.9; 14.8) 

29 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

April 1 to May 26 
2023 

May 1 to June 25 
2023 

June 1 to July 26 
2023 

24.3%  

(-93.4; 70.4) 

-11.9%  

(-158.5; 51.6) 

-30.8%  

(-625.6; 76.4) 

- 

- 

- 

- 

- 

- 

22.6% 

34.1%  

(-95.6; 69.4) 

(-82; 76.2) 

-12.5%  

-10.6% 

(-159.5; 51.2) 

 (-159.5; 52.8) 

-32.2%  

-8.8%  

(-622.7; 75.8) 

(-574.2; 82.4) 

- 

- 

- 

12–24 
weeks 

14.7%  

>24 weeks 

Overall 

<12 weeks 

12–24 
weeks 

>24 weeks 

33.3% 

-4.2% 

(-204; 76.1) 

 (-81.9; 75.5) 

 (-77.9; 39) 

-42.1%  

-13.7% 

11.1% 

(-205.3; 33.9) 

 (-167.5; 51.7) 

 (-39.7; 43.4) 

- 

-11.8% 

-172.8% 

 (-579.1; 81.6) 

 (-2170.8; 67.2) 

- 

- 

- 

- 

- 

- 

-61.3%  

(-333.5; 40 

14.0% 

(-42.6; 48.1) 

-213.4%  

(-3242.4; 70.6) 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago. 

Table 11. Relative* vaccine effectiveness (95% confidence intervals) in those aged 65–79 years against COVID-19-related death of the first, second and 
third booster dose, April 2022 and July 2023 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

April 1 to May 26 2022 

May 1 to June 25 2022 

June 1 to July 26 2022 

July 1 to August 25 
2022 

August 1 to September 
25 2022 

September 1 to October 
26 2022 

30 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

66.0% 

(55.2; 74.3) 

45.8% 

(30.3; 57.9) 

45.7% 

(-7.3; 72.5) 

47.5% 

(-37.9; 80) 

27.2% 

(-215.3; 83.2) 

-33.0% 

(-111.8; 16.5) 

64.0% 

(38.6; 78.9) 

- 

-25.0% 

(-123.1; 30) 

- 

- 

- 

75.4% 

(51.8; 87.5) 

52.9% 

(9; 75.6) 

-6.7% 

(-96; 41.9) 

-110.0% 

(-282.7; -15.2) 

- 

- 

21.5% 

(-355.5; 86.5) 

52.7% 

(36.7; 64.6) 

50.4% 

(8.4; 73.1) 

49.8% 

(-26.6; 80.1) 

27.3% 

(-206.3; 82.8) 

-34.0% 

(-114; 16.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

 
   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Study period 

October 1 to November 
25 2022 

November 1 to 
December 26 2022 

December 1 2022 to 
January 25 2023 

January 1 to February 
25 2023 

February 1 to March 28 
2023 

March 1 to April 25 
2023 

April 1 to May 26 2023 

May 1 to June 25 2023 

June 1 to July 26 2023 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

-8.5% 

(-69.6; 30.6) 

32.2% 

(-16.3; 60.5) 

32.3% 

(14.9; 46.1) 

25.2% 

(-13.8; 50.8) 

44.4% 

(14.6; 63.8) 

47.7% 

(19.8; 65.9) 

49.7% 

(0.2; 74.7) 

48.0% 

(-6; 74.5) 

38.1% 

(-16.7; 67.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

-34.2% 

(-112.6; 15.3) 

21.9% 

(-68.5; 63.8) 

18.3% 

(-20.6; 44.6) 

-11.3% 

(-130.3; 46.2) 

-26.7% 

(-209.9; 48.2) 

42.5% 

(11.4; 62.7) 

47.1% 

(-0.9; 72.3) 

46.8% 

(-3; 72.5) 

37.4% 

(-18.5; 66.9) 

60.6% 

(28.8; 78.2) 

82.9% 

(68.3; 90.8) 

74.9% 

(51.1; 87.1) 

65.6% 

(52.5; 75.1) 

68.7% 

(49.8; 80.4) 

62.9% 

(38.7; 77.6) 

51.5% 

(9; 74.2) 

30.6% 

(-22.2; 60.6) 

27.3% 

(-36.9; 61.4) 

61.0% 

(29.3; 78.5) 

79.9% 

(65.6; 88.3) 

76.0% 

(66.9; 82.6) 

72.0% 

(47.2; 85.2) 

- 

- 

- 

- 

- 

- 

75.2% 

(42.5; 89.3) 

60.2% 

(45.2; 71) 

61.0% 

(25.1; 79.7) 

62.9% 

(-89; 92.7) 

80.2% 

(60.4; 90.1) 

57.0% 

(23.3; 75.9) 

- 

- 

- 

- 

-49.2% 

(-121.1; -0.6) 

22.1% 

(-69.9; 64.3) 

49.0% 

(14.6; 69.5) 

50.2% 

(16.1; 70.5) 

49.9% 

(1.1; 74.7) 

28.0% 

(-27.1; 59.2) 

29.1% 

(-34.1; 62.5) 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago.  

31 

 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Table 12. Relative* vaccine effectiveness (95% confidence intervals) in those aged 50–64 years against COVID-19-related death of the first, second and 
third booster dose, April 2022 and July 2023 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

April 1 to May 26 2022 

May 1 to June 25 2022 

June 1 to July 26 2022 

July 1 to August 25 
2022 

August 1 to September 
25 2022 

September 1 to October 
26 2022 

October 1 to November 
25 2022 

November 1 to 
December 26 2022 

December 1 2022 to 
January 25 2023 

January 1 to February 
25 2023 

February 1 to March 28 
2023 

32 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

73.8% 
(-31.6; 94.8) 

3.2% 
(-387.9; 80.8) 

- 

48.8% 
(-7.9; 75.7) 

-14.8% 
(-588.8; 80.9) 

31.8% 
(-137.1; 80.4) 

16.0% 
(-206; 76.9) 

-17.2%  
(-141.3; 43.1) 

31.5%  
(-10.8; 57.7) 

1.2%  
(-90; 48.7) 

42.9% 
 (-19.8; 72.8) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

48.0% 
(-11.2; 75.7) 

-17.6% 
(-637.1; 81.2) 

30.0% 
(-153.4; 80.7) 

5.6% 
(-324.4; 79) 

-36.4%  
(-183.3; 34.3) 

20.4%  
(-80.8; 64.9) 

-20.1% 
 (-137.4; 39.2) 

18.6%  
(-195.9; 77.6) 

- 

- 

- 

- 

- 

- 

- 

34.6% 
(-74; 75.5) 

62.7%  
(24.7; 81.5) 

55.6%  
(0.2; 80.3) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

 
   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                             COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

March 1 to April 25 
2023 

April 1 to May 26 2023 

May 1 to June 25 2023 

June 1 to July 26 2023 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

51.2% 
 (-18.8; 80) 

34.8%  
(-96.7; 78.4) 

5.6% 
 (-157.8; 65.4) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

59.8%  
(-6.7; 84.9) 

36.1% 
(-96.4; 79.2) 

0.0% 
 (-215.4; 68.3) 

- 

-1898.6% 
 (-Inf; 98.9) 

30.2% 
 (-98.8; 75.5) 

-7.4%  
(-210.1; 62.8) 

-86.0% 
 (-587.9; 49.7) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

* Relative vaccine effectiveness of first, second and third booster dose compared to complete primary vaccination series without booster administered ≥24 weeks ago.

33 

 
TECHNICAL REPORT 

       COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Main findings  

In this study, after April 2022, which was about six months after the first booster vaccination campaign that took 
place in most countries in the autumn of 2021, the additional protection conferred by this first booster compared 
to the level of protection seen among those who had only completed primary vaccination (at least 24 weeks 
earlier) with no subsequent booster had decreased to less than 50% and showed little or no additional protection 
as of July 2023. 

The second and third boosters each increased rVE to >70% compared to only primary vaccination in the groups 
≥65 years (55% in the group 50–64 years), shortly after the booster administration. The effectiveness for doses 
administered in autumn 2022 (when bivalent vaccines were used, both BA.1 and BA.4/5), was similar regardless 
of booster dose number (third booster dose administered in Belgium, Italy, Portugal, and the Netherlands, or 
second booster doses in other countries). This suggests that the time since the last dose could be more 
important than the total number of doses administered in the protection against both COVID-19 hospitalisation 
and death. However, their effect also waned rapidly to low or null. The only groups where protection was still 
significant as of July 2023 (only against hospitalisation) are among individuals 65–79 years with a first or a 
second booster dose (compared to complete primary vaccination without boosters) and, in a sensitivity analysis 
restricted to the six sites that contributed throughout the whole study period, among individuals ≥80 years with 
a second booster dose.  

These differences (with residual protection estimated first or second booster but not for third booster) probably 
reflect the uncontrolled selection of different populations accepting the successive booster doses, rather than 
true differences in the effectiveness of different boosters or in different age groups. The higher proportion of 
individuals with comorbidities among those with a third booster, the lower uptake in people with past infection, 
particularly if recent, and vaccination of individuals in the comparison group during the vaccination campaigns 
may explain the more rapid decrease and lower magnitude of rVE for the third boosters. Further analyses 
focusing on the additional VE regardless of number of doses have been planned for the upcoming season.  

Challenges, limitations  

The multi-country approach for VE monitoring using data routinely collected in EHR and according to a common 
protocol, offers multiple advantages. The increased sample size allows to monitor less frequent events by pooling 
results from several countries, also achieving good comparability across participating sites. Nonetheless, the 
number of events was sometimes too low to provide estimates with good precision. This occurred for rVE against 
COVID-19-related death in younger age groups or when using as reference group individuals with complete 
primary vaccination only, particularly among those aged ≥80 years, due to the high uptake of boosters in this 
age group in the participating countries.  

The rapid availability of data in EHR allows a near-real-time monitoring to support decision-making, which is only 
delayed by the time needed for severe outcomes to occur after SARS-CoV-2 infection and by the time needed for 
data consolidation. In our study, we allowed a minimum of one month between the end of the study period and the 
data extraction, thus allowing to analyse an observation period covering the time from three days up to one month 
before the time of data analysis. In the current epidemiological context, with a reduced number of events captured 
during the pre-defined eight-week observation periods, longer observation times may be needed to be able to reach 
precise estimates of rVE. Moreover, less frequent estimates (i.e. less than monthly) may be acceptable and timely 
enough to guide decision-making, suggesting the need to re-evaluate the monitoring strategy. 

However, using EHR also presents some challenges. Data are not collected for epidemiological study purposes, but 
rather for patient clinical management or resources assessment. Data extraction and coding by intermediate 
institutions imply some heterogeneity in the way variables are defined across sites (e.g. comorbidity variables were 
usually pre-coded at country level). This means adjustment may not be equally accurate or comparable across sites. 
On the other hand, because these pre-coded categories were often used to target vulnerable groups for vaccination, 
allowing them to vary from site to site may provide better internal validity. The multisite approach implies that the 
relative contribution of the study sites is different for the different vaccination statuses over time, which can make 
interpretation complex, but is also an opportunity to compare the effectiveness of vaccine doses across countries 
with different vaccine roll-out calendars (i.e. second and third booster campaigns deployed simultaneously in 
different countries). Finally, the heterogeneity between sites may be related to factors not captured in this study 
such as different local SARS-CoV-2 epidemiology and/or different control measures in place. 

Additionally, EHR are less flexible than primary data collection to include new variables, and some relevant 
aspects are missing such as previous SARS-CoV-2 infections or corresponding data (such as date of infection), 
the infecting SARS-CoV-2 variant, comorbidities (in one study site), or socioeconomic variables, among others. 

Another limitation of using EHR for VE estimations is the misclassification of hospitalisations not due to COVID-19 
as events of interest. To minimise this, outcomes of interest were restricted to hospital admissions in which the 

34 

TECHNICAL REPORT 

       COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

main cause was COVID-19 or SARI with positive SARS-CoV-2 test. Because the cause of death was not available 
in a timely manner in most countries, it is likely that deaths in which SARS-CoV-2 was detected but was not the 
primary cause of death have been incorrectly included as events in the study. Regarding case ascertainment, it is 
also relevant to consider that, with the evolution of the pandemic and the reduction in systematic use of SARS-
CoV-2 tests in the hospital setting, the probability of misclassification of events may increase.  

The different roll-outs of COVID-19 vaccine boosters in the different participating countries needs to be taken 
into account in this multi-country collaboration. For example, the rVE of the second and the third boosters during 
the autumn 2022 was very similar, which could be misinterpreted as no additional benefit of the third booster 
dose. However, the third booster dose was only administered to people with a second booster during the 
previous spring vaccination campaign in the countries that implemented it, thus representing different 
populations, with higher probability to accept repeated boosters. These results suggest that recent administration 
of a vaccine in autumn 2022 was equally effective, regardless of the number of previous doses (if it was the 
second or the third booster dose), and probably that the time since vaccination is more relevant to protection 
against COVID-19 than the number of doses. 

Finally, despite the adjustment by comorbidities and limiting the estimates to the population eligible for an 
additional booster dose at each point in time, it is possible that people who received an additional vaccine dose 
were different from those who did not receive it regarding the risk of severe COVID-19 outcomes, in ways not 
adjusted for in this study. This can be more relevant with the higher number of doses, when vaccination 
coverage decreases and/or vaccination campaigns are limited to the more vulnerable groups. Further, it is likely 
that people who received successive vaccinations close in time did not have any mild SARS-CoV-2 infection in the 
meantime, having less benefit from hybrid immunity [12]. On the other hand, the reference group for the rVE 
estimations are those with a previous vaccination ≥24 weeks ago with no boosters, who may correspond more 
likely to individuals with no comorbidities and low self-perceived risk, or who have had SARS-CoV-2 infections 
post-vaccination and decided (or were recommended by national vaccination policies) to postpone booster 
vaccination. Changing in SARS-CoV-2 local testing recommendations and the increase in the use of self-tests that 
are not captured in EHR is likely to have resulted in previous infection probably being highly misclassified, and 
adjustment for this variable probably incomplete. In addition, adjustment by post-vaccination infection may bring 
additional methodological challenges [13,14]. 

All the above limitations could result in the underestimation of rVE and partially explain the low residual benefit 
from previous booster doses as well as the lower and more rapid waning of effectiveness of the third booster 
dose, which was only administered to population who opted for a second booster in the spring and a third dose 
later in the autumn in Belgium, Italy, the Netherlands, and Portugal. Nevertheless, it is also plausible that a lower 
rVE in the most recent study period is caused by a higher circulation in Europe of XBB (and XBB1.5), which is 
associated with a higher immune escape [15]. 

Conclusions 

Overall, estimates of rVE generated in this study indicate that booster doses were effective in restoring protection 
against both hospitalisation due to COVID-19 and COVID-19-related death [15,16]. However, rVE point estimates 
declined over time, particularly for the third booster dose, which was only administered to the population ≥65 
years in Italy and the Netherlands and to population ≥80 years in Belgium and Portugal. Although there is 
uncertainty about the timing and the magnitude of the waning of immunity, due to a possible underestimation of 
the rVE, these results clearly support the policy of providing additional boosters periodically to maintain 
protection, especially to those ≥80 years, as they have an increased risk of severe outcomes.  

35 

 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update        TECHNICAL REPORT 

References 

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2. 

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4. 

5. 

6. 

7. 

8. 

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11. 

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European Centre for Disease Prevention and Control (ECDC). Protocol for a COVID-19 vaccine 
effectiveness study using health data registries: version 1.0. Stockholm: ECDC; 2023. Available at: 
https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-vacine-effectivenessvebis-study-
health-registries-data.pdf 
European Centre for Disease Prevention and Control (ECDC). Pilot protocol for a COVID-19 vaccine 
effectiveness study using health data registries: version 1.0. Stockholm: ECDC; 2022. Available at: 
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19%20vaccine%20effectiveness%20study%20using%20routinely%20collected%20vaccination%20status.pdf 
World Health Organization European Region (WHO Euro). COVID-19 situation in the WHO European 
Region [cited 2023 Jun 19]. Available at: 
https://www.arcgis.com/apps/dashboards/ead3c6475654481ca51c248d52ab9c61 
European Centre for Disease Prevention and Control (ECDC). COVID-19 Vaccine Tracker [cited 19 Jun 
2023]. Available at: https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-
tracker.html#uptake-tab  
European Medicines Agency. COVID-19 Vaccines [cited 2023 Jun 19]. Available at: 
https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-
covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-authorised#authorised-covid-19-
vaccines-section%0Ahttps://www.ema.europa.eu/en/human-regulato 
EMA and ECDC join forces for enhanced post-marketing monitoring of COVID-19 vaccines in Europe. 
Press release 2022. Available at: https://www.ecdc.europa.eu/en/news-events/ema-and-ecdc-join-forces-
enhanced-post-marketing-monitoring-covid-19-vaccines-europe 
COUNCIL RECOMMENDATION of 7 December 2018 on strengthened cooperation against vaccine-
preventable diseases (2018/C466/01) Available at: https://eur-lex.europa.eu/legal-
content/EN/TXT/PDF/?uri=CELEX:32018H1228(01) 
REGULATION (EU) 2022/2370 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 23 November 
2022 amending Regulation (EC) No 851/2004 establishing a European centre for disease prevention and 
control Available at: https://eur-lex.europa.eu/legal-
content/EN/TXT/PDF/?uri=CELEX:32022R2370&qid=1670582843806&from=EN 
Kislaya I, Sentís A, Starrfelt J, Nunes B, Martínez-Baz I, Nielsen KF, AlKerwi A, Braeye T, Fontán-Vela M, 
Bacci S, Meijerink H, Castilla J, Emborg HD, Hansen CH, Schmitz S, Van Evercooren I, Valenciano M, 
Nardone A, Nicolay N, Monge S; VEBIS‐Lot4 working group. Monitoring COVID-19 vaccine effectiveness 
against COVID-19 hospitalisation and death using electronic health registries in ≥65 years old population 
in six European countries, October 2021 to November 2022. Influenza Other Respir Viruses. 2023 
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Sentís A, Kislaya I, Nicolay N, Meijerink H, Starrfelt J, Martínez-Baz I, Castilla J, Nielsen KF, Hansen CH, 
Emborg HD, Nardone A, Derrough T, Valenciano M, Nunes B, Monge S; VEBIS-Lot4 working group. 
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Surveill. 2022 Jul;27(30):2200551. 
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19-vaccine-effectiveness-hospitalisation.pdf  
Bobrovitz N, Ware H, Ma X, et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid 
immunity against the omicron variant and severe disease: a systematic review and meta-regression. 
Lancet Infect Dis. 2023;23(5):556-567. 

13.  Monge S, Pastor-Barriuso R, Hernán MA. The imprinting effect of covid-19 vaccines: an expected selection 

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bias in observational studies. BMJ. 2023 Jun 7;e074404.  
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Uraki R, Ito M, Furusawa Y, Yamayoshi S, Iwatsuki-Horimoto K, Adachi E, et al. Humoral immune evasion 
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36 

TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first 
update 

Annex 1. Data sources used in the eight study sites to extract the 
study variables 

Type of 
variables 

Outcomes 

Study variable 

Study site 

Belgium 

Denmark 

Italy 

Luxembourg 

Navarra (Spain) 

The Netherlands 

Norway* 

Portugal  

Hospital 
admission due to 
COVID-19 

Clinical Hospital Survey 
database 

Death due to 
COVID-19 

NA 

Danish National 
Patient 
Register 
(DNPR) 

MiBA and 
Danish Civil 
Registration 
System (CPR)  

National 
Integrated 
COVID-19 
Surveillance 
Databases 

National 
Integrated 
COVID-19 
Surveillance 
Databases 

Epidemiological 
national surveillance 
platform (MSINF) to 
collect daily data from 
hospitals 

Enhanced COVID 
surveillance with 
individual revision 
of events 

NICE COVID-19 
registration 

Norwegian Intensive Care 
and Pandemic Registry 
(NIPaR) 

National Hospital 
Discharge database 
(BIMH) 

Idem + death 
certificate for death 
happened outside 
hospital or nursing 
home 

NA 

Administrative 
database of deaths 
and individual 
revision of events 

Norwegian Death Registry 
(DÅR) 

National Death Registry 
(SICO) and National Health 
Service User databaset 
(NHSU): a Cause of death 
is from SICO, death status 
and date of death from 
NHSU.  

Exposures 

Vaccination 
status 

National vaccine registry 
(VACCINNET) 

Danish 
Vaccination 
Registry (DVR) 

National 
Vaccination 
Registry 

MSVAC: National 
vaccination registry  

Vaccination 
register 

COVID-19 vaccination 
registry (CIMS) 

The National Immunisation 
Register (SYSVAK) 

The National Vaccination 
Register (VACINAS) 

Variables for 
adjustment or 
stratification 

Age 

Sex 

Health Region  

The national population 
register 

national population 
register 

Province of residence:  
national population 
register 

CPR 

CPR 

CPR 

National 
Vaccination 
Registry 

National 
Vaccination 
Registry 

Statutory health 
insurance database 

Administrative 
database 

The national population 
register 

The National Population 
Register (Folkeregisteret) 

National Health Service 
User databaset (NHSU) 

Statutory health 
insurance database 

Administrative 
database 

The national population 
register 

The National Population 
Register (Folkeregisteret) 

National Health Service 
User databaset (NHSU) 

Region where 
vaccination took 
place 

Statutory health 
insurance database 

Not applicable 

NA 

County of residence at 
end of study period: The 
National Population 
Register (Folkeregisteret) 

Region of residence: 
National Health Service 
User databaset (NHSU) 

37 

 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

              TECHNICAL REPORT 

Type of 
variables 

Study variable 

Belgium 

Denmark 

Comorbidities 

Intermutualistic Agency 
database 

DNPR 

Previous 
infection 

COVID-19 Laboratory test 
results database from 
Healthdata.be register 

MiBA 

Others specific to 
the study site

NA 

Household income 
(according to tax records) 
categorised as low 
(lowest 40%), mid (middle 
30%), and high (highest 
30%): 
STATBEL database 

Italy 
National 
Vaccination 
Registry 

National 
Vaccination 
Registry 

National 
Integrated 
COVID-19 
Surveillance 
Databases 

Country of birth  
National 
Vaccination 
Registry 

Study site 

Luxembourg 

Navarra (Spain) 

The Netherlands 

Norway* 

Portugal  

Not applicable 

Primary Care 
Information System 

Specialised health care 
utilisation combined 
with prescribed 
medication register, 
both from 2020 

Risk groups / 
Comorbidities: Based on 
Norwegian Patient 
Registry (NPR) 

Primary Care Information 
System (SIM@SNS).  

MSINF (see above) 

NA 

Previous infections 
are excluded, 
pendent of a 
separate analysis 

The Surveillance System 
for Infectious Diseases 
(MSIS) 

National Information 
System for Epidemiologic 
Surveillance (BI-SINAVE) 

Statutory health 
insurance database 

Country of birth 
and high functional 
dependence:  
Administrative 
database 

Months of death and 
emigration from 
population registry, 
LTCF residency from 
Central Administration 
Office 

1. Conditions of living – 
Crowding: Statistics 
Norway (SSB). Most 
recent data from 2019 – 
separate level for missing 
data 
2. County of birth: 
Folkeregisteret 

1. Number of tests for 
SARS-CoV-2 in 2020-
2022: BI-SINAVE  
2. Conditions of living – 
Deprivation at municipality 
level: Most recent data 
from 2011 
3. Other vaccines uptake: 
VACINAS 

NA: not applicable.  
*All data in Norway were integrated in the emergency preparedness register for COVID-19 (Beredt C19): https://www.fhi.no/en/id/infectious-diseases/coronavirus/emergency-preparedness-register-
for-covid-19  

38 

   
 
 
 
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Annex 2. Methodological details in the different study sites 

Variable 

Definition, categorisation, use in the model 

Belgium 

Denmark 

Italy 

Luxembourg 

The Netherlands 

Navarra (Spain) 

Norway 

Portugal  

Age 

Comorbidities 

5–17, 18–49, 50–64, 65–
79, ≥80, adjusted in 
categories: 5–9, 10–14, 
15–17, 18–24 and then 
five-year categories until 
the final category, 90+ 
years 

Immunocompromised, 
including: 
-  HIV 
-  Immunological disease 
-  Radiation therapy 
-  Organ-transplanted 

Other, including: 
-  Diabetes 
-  Obesity 
-  Cancer 
-  Neurological Disease 
-  Kidney disease 
-  Haematological 

cancers 

-  Heart disease 
-  Chronic respiratory 

disease 

-  Liver disease (incl. 
alcohol lever) 
-  Endocrine Disease 
-  Hematological Disease 
-  Coagulation Disease  
-  Innate Diseases 
-  TB 
-  Missing a lung 
-  Missing a kidney 

Age in years at the end of the 
year in which the study 
period begins. 
For adjustment: five-year age 
groups. 

No comorbidities associated 
with an increased risk for 
severe COVID-19 infection. 

At least one comorbidity 
which increases the risk for 
severe COVID-19 infection 
and not being 
immunocompromised 
(medium risk):  
-  Received chemotherapy/ 
radiotherapy against 
cancer 

-  Received multidisciplinary 

oncologic consult 

-  Cardiovascular illness – 

general 

-  Cardiovascular illness- 
specifically a heart 
disease 
-  Alzheimer 
-  Asthma 
-  Haemophilia 
-  Disease of Crohn, Colitis 
Ulcerosa, Psoriatrische 
arthritis, Reumatoid 
arthritis 

-  Chronic obstructive 
pulmonary disease 

-  Diabetes with 
cardiovascular 
compilations 

Age at the start of study 
period (for adjustment: five-
year age groups up to 90–
94 years and then grouping 
≥95 years)) 

Age at the start of 
follow up, five-year 
categories 

Age at the start of 
study period (five-
year categories) 

Age at the start of 
study period (five-year 
categories) 

Age at end of 2022 (birth 
cohorts) (For adjustment: 
five-year age groups) 

Age at the start of 
study period (five-
year categories) 

Immuno-compromised 

Other major chronic 
conditions 
- 
- 
- 
- 
- 
- 
- 

Diabetes 
Severe Obesity 
Cancer 
Ictus 
Dementia 
Kidney disease 
Haematological 
cancers 
Heart disease 
Chronic 
respiratory 
disease 
Liver disease 
Rheumatic 
arthritis 

- 
- 

- 
- 

Three-level variable 
(no risk, medium 
risk, high risk) 
Medium risk is 
defined as eligibility 
for influenza 
vaccination based 
on comorbid 
conditions. High 
risk is defined as 
comorbid 
conditions based 
on increased risk of 
severe covid. 
Methods, data and 
codes used are 
extensively 
described in the 
article by de Gier et 
al [16]. 

Immunocompromised, 
including: 

Not included 

-  Immunocompromised 

defects of the 
complement system 

-  Other specified 

disorders involving the 
immune mechanism 

-  Deficiency or 

dysfunction of a single 
component (C1-C9) 

-  Deficiency of cell-

mediated immunity 
-  Deficiency of humoral 

immunity 

-  Human 

immunodeficiency virus 
[HIV] disease, Human 
immunodeficiency virus, 
type 2 [HIV-2], 
Asymptomatic human 
immunodeficiency virus 
[HIV] infection status 
-  Disorders involving the 
immune mechanism 
-  Congenital and acquired 

disorders with poor 
antibody production  

-  Drug-induced 

immunosuppression 

Number of 
comorbidities (0, 
1, 2, 3, 4, 5+) 

Considered 
comorbidities 
include: anemia, 
asthma, cancer, 
cardiac disease, 
dementia, 
diabetes, 
hypertension, HIV, 
liver disease, 
neuromuscular 
disease, obesity, 
pulmonary 
disease, renal 
disease, 
rheumatologic 
disease, stroke, 
tuberculosis 

High risk:  
-  Organ transplant 
Immunodeficiency 
- 
-  Haematological cancer 
in the last five years 
-  Other active cancers 
-  Neurological or 
neuromuscular 
diseases that cause 
impaired cough or lung 
function (e.g. ALS and 
cerebral palsy) 

-  Chronic kidney disease, 
or significant renal 
impairment. 

Medium risk:  
-  Chronic liver disease or 
significant hepatic 
impairment 
Immunosuppressive 
therapy 
-  Diabetes 
-  Chronic lung disease 

- 

including cystic fibrosis 
and severe asthma 
which have required the 
use of high dose 
inhaled or oral steroids 
within the past year 

39 

 
 
 
 
 
 
 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

Variable 

Definition, categorisation, use in the model 

Portugal  

Norway 
-  Obesity with a body 
mass index (BMI) of 
≥35 kg/m2 
-  Dementia 
-  Chronic heart and 

vascular disease (with 
the exception of high 
blood pressure) and 
stroke 

Belgium 
-  Diabetes Mellitus with 
insulin treatment 

-  Epilepsy and neuropathic 

pain 

-  Chronic hepatitis type B or 

C 

-  Kidney failure 
-  Cystic fibrosis 
-  Exocrine pancreatic 

disease 

-  Disease of Parkinson 
-  Psoriasis 
-  Psychosis occurring with 
people older than 70 
years 

-  Psychosis occurring with 
people of 70 years or 
younger 

-  Multiple sclerosis 
-  Thrombosis while treated 

with antithrombotic 
medicines 

-  Thyroid disorder 
-  HIV 
-  Immunocompromised 
(high risk): if a person 
received a priority 
invitation for a COVID-19 
vaccination due to being 
immunocompromised, 
then he/she was classified 
into a this group. 

40 

Denmark 

Italy 
Other comorbidities, 
including: 

Luxembourg 

The Netherlands 

Navarra (Spain) 

-  Respiratory diseases 
requiring oxygen 
therapy, idiopathic 
pulmonary fibrosis 
-  Advanced heart failure 
(Classes III-IV NYHA) 
and post cardiogenic 
shock patients  
-  Amyotrophic lateral 
sclerosis and other 
motor neuron disorders, 
multiple sclerosis, 
muscular dystrophy, 
infantile cerebral palsy, 
myasthenia gravis, 
dysimmune 
neuropathies  

-  Type 1 diabetes, Type 2 

diabetes with 
complications or 
requiring combination 
therapy (with at least 
two anti-diabetes drugs) 

-  Addison's disease 
-  Panhypopituitarism  
-  Cystic fibrosis 
-  -Cirrhosis of the liver  
-  Intracerebral ischemic 
or hemorrhagic event 
that has led to impaired 
neurological and 
cognitive autonomy  
-  Individuals who have 

had a stroke on 2020 or 
later ranked as level 3 
or higher 

-  Thalassemia major 
-  Sickle cell anemia 
-  Other severe anemias 
-  Down syndrome  
-  Body Mass Index >35  
-  Severely disabled 

persons pursuant to law 

   
 
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Variable 

Definition, categorisation, use in the model 

Belgium 

Denmark 

Italy 

Luxembourg 

The Netherlands 

Navarra (Spain) 

Norway 

Portugal  

104/1992 art. 3 
paragraph 3  

-  Chronic Alcohol Misuse  
-  Functional or anatomic 

asplenia  

-  COPD  
-  Chemotherapy or 
Radiotherapy  
-  Coagulopathies  
-  Diabetes Mellitus and 

other endocrinopathies  
-  Patients in hemodialysis 
or with chronic kidney 
diseases expected to 
start dialysis  

-  Hemoglobinopathy such 
as sickle cell anemia or 
thalassemia  

-  Chronic Liver Disease  
-  Cochlear implant  
-  Chronic Kidney Disease  
-  Chronic eczema or 

psoriasis  

-  Diseases associated 
with a high risk of 
aspiration pneumonia  
-  Chronic Cardiovascular 

Disease  

-  Chronic Respiratory 

Disease  

-  Motor neuron diseases  
-  Chronic inflammatory 

diseases and 
malabsorption 
syndromes  
-  Blood cancers 

(leukemia, lymphoma 
and myeloma)  

-  Solid tumors  
-  Obesity (Body Mass 

Index 30-35)  

-  Bone marrow transplant  
-  Drug Misuse  
-  Solid organ transplant  

41 

 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

Variable 

Definition, categorisation, use in the model 

Belgium 

Denmark 

Italy 

Luxembourg 

The Netherlands 

Navarra (Spain) 

Norway 

Portugal  

Not included 

Not included 

Country of 
residence / 
country of birth / 
nationality 

-  Patients with CSF leak 

from trauma or 
intervention  

-  Patients going to start 
immunosuppressive 
treatment  

-  Metabolic diseases  
-  Hematopoietic diseases  
-  Pathologies that require 

important surgical 
interventions  

-  Neurological diseases  
-  Cerebrovascular 

diseases  

-  Down Syndrome 
-  Disabilities (physical, 
sensorial, learning or 
psychic) 

Country of birth: born in 
Italy; born in other countries 

Country of 
residence = 
administrative 
address in 
Luxembourg (as of 
September 2021) 
Country of birth = 
Luxembourg / 
Other 
Nationality = 
Citizenship 
Luxembourg / 
Other 

Not included 

Country of birth 

As registered at time of 
analysis (June 2022) 

Not included 

Deprivation index 
or similar 

Household income: low 
(lowest 40%)-medium 
(middle 30%)-high (highest 
30%) 

Not included 

Not included 

Not included 

Not included 

High functional 
dependence 

European 
deprivation index 
quintile  Q1 (least 
deprived) to Q5 
(most deprived) 

Crowded conditions: if the 
number of rooms is lower 
than the number of 
residents or one resident 
lives in one room, and the 
number of square metres 
(P-area) is below 25 sq. m. 
per person. If the number 
of rooms or the P-area is 
not specified, a household 
was regarded as crowded 
if one of these criteria is 

42 

   
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Variable 

Definition, categorisation, use in the model 

Belgium 

Denmark 

Italy 

Luxembourg 

The Netherlands 

Navarra (Spain) 

Norway 
met (incomplete and 
slightly outdated data) 

Portugal  

Geographic level 

Province of residence 

Adjustment for residency 
in the 5 geographical 
regions of Denmark (EU 
NUTS-2 regions) 

19 regions and two 
autonomous provinces of 
Italy where vaccination took 
place 

Canton 

Not included 

Not included 

County of residence 

Other vaccines 
uptake 

Not included 

Not included 

Not included 

Not included 

Not included 

Not included 

Not included 

Region of 
residence (North, 
Centre, Lisbon 
and Tagus Valey, 
Alentejo, Algarve) 

Vaccination 
against influenza, 
PCV7, PCV10, 
PCV13 or PPV23 
in the last three 
years  

Number of 
COVID-19 tests in 
2020-2022 

Not included 

Positive RT-PCR test for 
SARS-CoV-2 

Not included 

Not included 

Not included 

Not included 

Not included 

0, 1, 2, 3, 4-9, 10+ 

43 

 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

Annex 3. Numbers of individuals, COVID-19 related deaths and 
person-months by eight-week period, between April 2022 to July 
2023, by age group 

Age 
group 

Study period 

Primary vaccination without booster ≥24 
weeks 

Complete vaccination 
+ first booster 

Complete vaccination 
+ two booster doses 

Complete vaccination 
+ three booster doses 

N 

Events/ 
person-month 

Apr to May 2022 

58 361 

May to Jun 2022 

65 577 

Jun to Jul 2022 

63 671 

Jul to Aug 2022 

63 625 

Aug to Sep 22 

62 265 

Sep to Oct 22 

60 265 

Oct to Nov 22 

52 839 

Nov to Dec 22 

60 673 

Dec 22 to Jan 23 

Jan to Feb 23 

429 927 

424 704 

≥ 80 

44 

175/ 
96 037 

222/ 
102 836 

177/ 
101 232 

96/ 
109 291 

59/ 
108 984 

55/ 
98 519 

51/ 
90 233 

71/ 
106 489 

204/ 
774 124 

109/ 
768 764 

N 

1 017 584 

1 031 854 

883 489 

740 744 

696 778 

607 410 

452 513 

214 422 

2 158 678 

2 064 013 

Events/ 
person-month 

1 397/ 
1 848 699 

1 480/ 
1 636 612 

923/ 
1 277 984 

600/ 
1 276 266 

320/ 
1 153 938 

268/ 
785 472 

228/ 
464 819 

234/ 
311 223 

1 140/ 
3 776 125 

528/ 
3 682 615 

N 

- 

- 

341 905 

408 209 

488 519 

579 689 

501 043 

609 353 

2 188 895 

2 168 881 

Events/ 
person-month 

- 

- 

247/ 
425 607 

227/ 
658 215 

190/ 
729 420 

174/ 
660 644 

179/ 
610 239 

361/ 
1 024 948 

1 063/ 
3 740 739 

560/ 
3 839 081 

N 

- 

- 

- 

- 

- 

- 

259 940 

271 444 

450 091 

481 156 

Events/ 
person-month 

- 

- 

- 

- 

- 

- 

121/ 
391 152 

189/ 
466 658 

218/ 
709 232 

180/ 
823 152 

   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Age 
group 

Study period 

Primary vaccination without booster ≥24 
weeks 

Complete vaccination 
+ first booster 

Complete vaccination 
+ two booster doses 

Complete vaccination 
+ three booster doses 

Feb to Mar 23 

Mar to Apr 23 

Apr to May 23 

May to Jun 23 

Jun to Jul 23 

N 

421 752 

420 965 

419 649 

416 699 

415 804 

Apr to May 22 

138 587 

May to Jun 22 

175 656 

Jun to Jul 22 

191 889 

Jul to Aug 22 

204 930 

Aug to Sep 22 

205 096 

Sep to Oct 22 

202 968 

Oct to Nov 22 

191 550 

Nov to Dec 22 

204 585 

Events/ 
person-month 

N 

Events/ 
person-month 

N 

Events/ 
person-month 

64/ 
764 927 

52/ 
764 364 

32/ 
762 591 

32/ 
757 364 

23/ 
756 047 

70/ 
224 508 

76/ 
263 982 

59/ 
303 450 

41/ 
356 594 

25/ 
370 298 

23/ 
345 006 

25/ 
298 826 

45/ 
344 948 

2 018 434 

2 008 943 

2 008 651 

1 989 387 

1 990 890 

1 841 200 

2 660 119 

2 619 538 

2 773 095 

2 765 211 

2 699 610 

2 035 729 

1 069 168 

330/ 
3 657 445 

276/ 
3 654 651 

165/ 
3 657 053 

155/ 
3 620 456 

91/ 
3 626 217 

377/ 
3 357 694 

499/ 
4 913 682 

173/ 
2 910 279 

323/ 
5 091 730 

244/ 
4 941 744 

243/ 
3 968 103 

169/ 
1 922 702 

166/ 
1 344 492 

2 113 944 

2 100 556 

2 077 413 

1 827 436 

1 799 882 

- 

- 

- 

- 

260 763 

0 

1 541 106 

2 180 996 

416/ 
3 815 297 

413/ 
3 816 488 

301/ 
3 755 342 

217/ 
3 279 901 

130/ 
3 272 266 

- 

- 

- 

- 

12/ 
196 709 

<5/0 

60/ 
1 443 320 

132/ 
3 563 394 

N 

491 382 

493 848 

495 165 

493 433 

490 679 

- 

- 

- 

- 

- 

- 

- 

- 

65-79 

Events/ 
person-month 

210/ 
871 606 

188/ 
890 191 

141/ 
899 543 

136/ 
896 559 

127/ 
893 761 

- 

- 

- 

- 

- 

- 

- 

- 

45 

 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

Age 
group 

Study period 

Primary vaccination without booster ≥24 
weeks 

Complete vaccination 
+ first booster 

Complete vaccination 
+ two booster doses 

Complete vaccination 
+ three booster doses 

Dec 22 to Jan 23 

Jan to Feb 23 

Feb to Mar 23 

Mar to Apr 23 

Apr to May 23 

May to Jun 23 

Jun to Jul 23 

N 

938 113 

934 452 

928 449 

931 653 

935 429 

921 517 

924 488 

Apr to May 22 

327 750 

May to Jun 22 

344 451 

50-64 

Jun to Jul 22 

358 093 

Jul to Aug 22 

669 900 

Aug to Sep 22 

664 092 

Sep to Oct 22 

659 605 

46 

Events/ 
person-month 

N 

Events/ 
person-month 

N 

Events/ 
person-month 

90/ 
1 694 435 

56/ 
1 699 564 

42/ 
1 696 136 

27/ 
1 703 449 

24/ 
1 710 882 

16/ 
1 686 000 

13/ 
1 692 300 

8/ 
565 383 

8/ 
584 101 

4/ 
610 379 

12/ 
1 151 030 

12/ 
1 206 551 

15/ 
1 187 926 

6 115 214 

5 840 533 

5 694 754 

5 501 784 

5 647 928 

5 430 605 

5 439 476 

2 098 543 

2 104 957 

906 491 

2 247 438 

2 251 885 

2 251 285 

503/ 
10 702 984 

289/ 
10 453 115 

201/ 
10 366 555 

121/ 
10 057 298 

77/ 
10 339 556 

60/ 
9 941 579 

42/ 
9 959 824 

19/ 
3 838 848 

15/ 
3 864 131 

13/ 
1 672 935 

34/ 
4 157 885 

30/ 
4 171 008 

34/ 
3 847 105 

4 587 699 

4 663 817 

4 647 111 

4 150 732 

4 552 049 

3 413 552 

3 404 875 

- 

- 

- 

- 

- 

- 

310/ 
7 942 353 

195/ 
8 317 321 

171/ 
8 456 564 

161/ 
7 597 085 

162/ 
8 312 664 

98/ 
6 246 009 

78/ 
6 233 768 

- 

- 

- 

- 

- 

- 

N 

111 014 

Events/ 
person-month 

5/ 
135 118 

0 

0 

0 

0 

0 

0 

- 

- 

- 

- 

- 

- 

<5/0 

<5/0 

<5/0 

<5/0 

<5/0 

<5/0 

- 

- 

- 

- 

- 

- 

   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Age 
group 

Study period 

Primary vaccination without booster ≥24 
weeks 

Complete vaccination 
+ first booster 

Complete vaccination 
+ two booster doses 

Complete vaccination 
+ three booster doses 

N 

Events/ 
person-month 

Oct to Nov 22 

652 814 

Nov to Dec 22 

653 950 

Dec 22 to Jan 23 

Jan to Feb 23 

Feb to Mar 23 

Mar to Apr 23 

Apr to May 23 

May to Jun 23 

Jun to Jul 23 

2 320 101 

2 287 477 

2 262 496 

2 256 159 

2 284 065 

2 224 708 

2 232 487 

8/ 
1 172 401 

14/ 
1 144 119 

22/ 
4 185 536 

14/ 
4 177 978 

13/ 
4 141 950 

14/ 
4 133 048 

12/ 
4 185 708 

5/ 
4 074 734 

3/ 
4 090 485 

N 

2 223 597 

2 422 428 

10 127 026 

9 709 827 

9 296 680 

9 237 724 

9 345 725 

9 348 466 

723 048 

Events/ 
person-month 

N 

Events/ 
person-month 

26/ 
3 194 991 

40/ 
3 658 08 

112/ 
17 827 142 

68/ 
17 613 547 

39/ 
16 988 111 

29/ 
16 912 086 

18/ 
17 124 701 

24/ 
17 130 208 

12/ 
1 324 775 

588 203 

1 230 727 

1 664 929 

2 415 107 

711 253 

2 405 075 

2 385 575 

1 735 159 

704 038 

7/ 
492 583 

16/ 
1 514 380 

23/ 
2 808 957 

17/ 
4 288 779 

8/ 
1 288 753 

17/ 
4 411 359 

19/ 
4 389 030 

17/ 
3 176 602 

15/ 
1 290 080 

N 

- 

- 

- 

- 

- 

- 

- 

- 

- 

Events/ 
person-month 

- 

- 

- 

- 

- 

- 

- 

- 

- 

47 

 
 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

Annex 4. Distribution of person-months in the study by covariates, 
from November 2022* to July 2023 

48 

   
 
 
 
 
 
TECHNICAL REPORT                                                                                                                                                COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

49 

 
  
 
 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

                    TECHNICAL REPORT 

*Information collected for all participating study sites from November 2022 onward.  

50 

   
 
 
 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Annex 5. Results restricted to the six study 
sites that contributed since the start of the 
study period 

Figure 1A. Relative vaccine effectiveness (95% confidence intervals) against hospitalisation due to 
COVID-19 of first, second and third booster dose, compared to complete primary vaccination series 
without booster administered ≥24 weeks ago, for each eight-week overlapping study period 
between April 2022 and July 2023, restricting to the six study sites that contributed since the start 
of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), Norway, and Portugal) 

51 

 
 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Figure 2A. Relative vaccine effectiveness (95% confidence intervals) against hospitalisation due to 
COVID-19 of the first, second and third booster dose, compared to complete primary vaccination 
without booster administered ≥24 weeks ago, by time since the booster, for each eight-week 
overlapping study period between April 2022 and July 2023, restricting to the six study sites that 
contributed since the start of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), 
Norway, and Portugal) 

52 

 
 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Figure 3A. Relative vaccine effectiveness (95% confidence intervals) against COVID-19-related 
mortality of the first, second and third booster dose, compared to complete primary vaccination 
administered ≥24 weeks ago without booster, for each eight-week overlapping study period, April 
2022 and July 2023, restricting to the six study sites that contributed since the start of the study 
period (Belgium, Denmark, Luxembourg, Navarra (Spain), Norway, and Portugal) 

53 

 
 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Figure 4A. Relative vaccine effectiveness (95% confidence intervals) against COVID-19 related 
mortality of the first, second and third booster dose, compared to complete primary vaccination 
administered ≥24 weeks ago without booster, by time since the booster, for each eight-week 
overlapping study period, April 2022 and July 2023, restricting to the six study sites that 
contributed since the start of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), 
Norway, and Portugal)  

54 

 
 
 
COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Table 1A. Relative vaccine effectiveness (95% Confidence Intervals) in ≥80 years against hospitalisation due to COVID-19 of the first, second and third 
booster dose, compared to complete primary vaccination without booster administered ≥24 weeks ago, for each eight-week overlapping study period 
between April 2022 and July 2023, restricting to the six study sites that contributed since the start of the study period (Belgium, Denmark, Luxembourg, 
Navarra (Spain), Norway, and Portugal) 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

>24 weeks 

12–24 
weeks 

1 April to 26 May 
2022 

52.2% 
(24.7; 69.6) 

54.7% 
(37.2; 67.3) 

54.6% 
(34.4; 68.5) 

47.8% 
(36.8; 56.9) 

1 May to 25 June 
2022 

42.2% 
(32.6; 50.5) 

72.0% 
(55.7; 82.3) 

41.4% 
(29.9; 51.1) 

39.3% 
(29.4; 47.8) 

- 

- 

- 

- 

44.1% 
(29.4; 55.7) 

- 

24.9% 
(-53.2; 63.1) 

41.8% 
(25.2; 54.7) 

71.0% 
(61.4; 78.2) 

71.0% 
(61.4; 78.2) 

37.5% 
(16; 53.5) 

70.0% 
(46.5; 83.2) 

28.3% 
(-2.9; 50.1) 

36.5% 
(14.6; 52.8) 

57.8% 
(48.2; 65.6) 

62.5% 
(52.7; 70.2) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

72.1% 
(60.6; 80.2) 

70.8% 
(60.2; 78.6) 

65.2% 
(53.1; 74.2) 

64.3% 
(51.9; 73.5) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

27.8% 
(10.4; 41.9) 

57.2% 
(43.1; 67.9) 

60.2% 
(45; 71.3) 

29.9% 
(11.7; 44.3) 

50.7% (35.8; 62. 
2) 

60.2% 
(46.9; 70.2) 

30.0% 
(-7.4; 54.3) 

41.8% 
(26.6; 53.9) 

68.4% 
(54.5; 78.1) 

75.6% 
(65.5; 82.8) 

38.7% 
(17.9; 54.2) 

47.2%  
(8.9; 69.4) 

31.9%  
(17.7; 43.6) 

71.6%  
(60.7; 79.4) 

76.0% 
 (69.8; 80.9) 

54.0%  
(36.5; 66.7) 

- 

- 

- 

- 

27.5%  
(10.4; 41.4) 

65.2%  
(52.3; 74.6) 

70.8%  
(61.4; 77.9) 

61.6%  
(50.5; 70.1) 

32.3% 
(-86.1; 75.4) 

52.3% 
(30.4; 67.4) 

52.8% 
(30.5; 68) 

41.0% 
(1.3; 64.7) 

28.2% 
(-2.1; 49.5) 

56.0% 
(41.3; 67.1) 

66.4% 
(47.8; 78.4) 

61.6% 
(32.6; 78.1) 

22.6% 
(-29; 53.6) 

33.8% 
(-2.9; 57.4) 

58.6% 
(28.9; 75.9) 

23.9% 
(-18.6; 51.2) 

10.4% 
(-33.3; 39.7) 

35.7% 
(8.7;54.8) 

35.3% 
(10.3; 53.4) 

36.5%  
(-11.4; 63.8) 

- 

- 

49.0% 
(26.7; 64.5) 

3.5% 
(-88.2; 50.6) 

-7.9% 
(-321.1; 72.3) 

44.6%  
(12.5; 65) 

6.4%  
(-92.6; 54.5) 

-19.8%  
(-550; 77.9) 

- 

- 

-12.1% 
(-319.2; 70) 

-15530.0%  
(-Inf; 99.8) 

1 June to 26 July 
2022 

1 July to 25 
August 2022 

1 August to 25 
September 2022 

1 September to 26 
October 2022 

1 October to 25 
November 2022 

1 November to 26 
December 2022 

1 December 2022 
to 25 January 
2023 
1 January to 25 
February 2023 

1 February to 28 
March 2023 

28.9% 
(11.8; 42.7) 

32.2% 
(14.9; 46) 

45.5% 
(31.4; 56.7) 

37.3%  
(24.4; 47.9) 

35.6%  
(18.2; 49.3) 

34.4% 
(1.7; 56.2) 

17.2% 
(-13.5; 39.6) 

1 March to 25 April 
2023 

6.2%  
(13.2; 53.2) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

-20.0%  
(-518; 76.7) 

55 

 
   
 
 
 
TECHNICAL REPORT

            COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Complete primary vaccination + three booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

1 April to 26 May 
2023 

31.2%  
(-15.5; 59) 

1 May to 25 June 
2023 

43.9%  
(-68.6; 81.3) 

1 June to 26 July 
2023 

49.9%  
(-19.6; 79) 

- 

- 

- 

- 

- 

- 

28.7% 
(-21.4; 58.1) 

39.6%  
(-17.4; 68.9) 

42.8% 
(-76; 81.4) 

38.4%  
(-48.6; 74.5) 

49.9% 
(-19.4; 79) 

57.8%  
(9.8; 80.2) 

- 

- 

- 

47.6%  
(-0.5; 72.7) 

39.1%  
(-19.6; 69) 

32.6%  
(-123.5; 79.7) 

- 

- 

36.7%  
(-53.6; 73.9) 

55.0%  
(-275.9; 94.6) 

56.9%  
(7.8; 79.8) 

- 

- 

- 

- 

12–24 
weeks 

-14.9%  
(-189.6; 54.4) 

- 

- 

>24 weeks 

-14.7%
(-270.2; 64.4) 

-37.0%
(-163.2; 28.7 

- 

56 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Table 2A. Relative vaccine effectiveness (95% Confidence Intervals) in 65-79 years against hospitalisation due to COVID-19 of the first, second and third 
booster dose, compared to complete primary vaccination without booster ≥24 weeks ago for each eight-week overlapping study period between April 2022 
and July 2023, restricting to the six study sites that contributed since the start of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), 
Norway, and Portugal) 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

1 April to 26 May 2022 

1 May to 25 June 2022 

1 June to 26 July 2022 

1 July to 25 August 
2022 

1 August to 25 
September 2022 

1 September to 26 
October 2022 

1 October to 25 
November 2022 

1 November to 26 
December 2022 

1 December 2022 to 25 
January 2023 

1 January to 25 
February 2023 

1 February to 28 March 
2023 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

64.2%  
(42.2; 77.8) 

47.1%  
(33.6; 57.8) 

34.6%  
(19.2; 47) 

47.5%  
(30.6; 60.3) 

43.2%  
(20.6; 59.3) 

18.6%  
(-8.1; 38.7) 

30.4%  
(9.8; 46.3) 

47.0%  
(33.7; 57.7) 

48.1%  
(22.5; 65.3) 

33.2% 
 (7.9; 51.6) 

-0.9%
(-40.3; 27.5) 

49.7%  
(18.7; 68.8) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

65.2%  
(42.7; 78.9) 

47.7%  
(25.5; 63.3) 

20.5%  
(-4.5; 39.6) 

12.9%  
-16.1; 34.6) 

- 

- 

- 

- 

- 

- 

- 

40.7%  
(-98.3; 82.3) 

47.6%  
(34.1; 58.4) 

36.0% 
 (20.9; 48.3) 

48.5%  
(31.6; 61.3) 

43.9%  
(21.3; 59.9) 

18.4%  
(-7.2; 37.8) 

27.8%  
(6.3; 44.4) 

40.9%  
(18.7; 57.1) 

42.5%  
(16.2; 60.5) 

29.6%  
(-3.2; 52) 

-13.4% 
 (-58.3; 18.7) 

- 

- 

- 

- 

22.7%  
(-29.6; 53.9) 

51.2% 
(9.9; 73.6) 

73.4% 
 (62.2; 81.3) 

79.1%  
(67.4; 86.7) 

74.5%  
(53.5; 86) 

63.9%  
(48.3; 74.7) 

44.2%  
(23.1; 59.6) 

- 

- 

- 

- 

68.4%  
(42.5; 82.6) 

65.1% 
 (34.3; 81.5) 

76.6%  
(66.5; 83.6) 

79.6%  
(74.4; 83.7) 

72.0%  
(48.6; 84.7) 

71.7%  
(53; 83) 

- 

- 

- 

- 

- 

- 

- 

- 

82.5%  
(30.4; 95.6) 

69.8%  
(60.1; 77.2) 

50.8%  
(13.9; 71.9) 

42.9%  
(18.1; 60.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

27.4% 
(-33.2; 60.4) 

43.1%  
(-7.9; 70) 

57 

TECHNICAL REPORT

            COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

1 March to 25 April 
2023 

1 April to 26 May 2023 

1 May to 25 June 2023 

1 June to 26 July 2023 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

-582.5% 
(-Inf; 90.9) 

19.9%  
(-14.3; 43.9) 

-8.8%
(-89.4; 37.5 

45.2%  
(-39.2; 78.4) 

- 

- 

- 

- 

- 

- 

- 

- 

16.8% 
(-10; 37.1) 

18.2% 
(-25.1; 46.5) 

-10.1%
(-91.4; 36.7) 

45.1%  
(-39.1; 78.4) 

53.5%  
(38; 65.1) 

45.0%  
(3.7; 68.5) 

24.8%  
(-29.2; 56.2) 

61.6%  
(7.2; 84.1) 

- 

- 

- 

- 

54.3%  
(39.4; 65.5) 

43.6%  
(-4.5; 69.6) 

4.7%  
(-102.6; 55.2) 

- 

52.8%  
(32.7; 66.9) 

46.5%  
(5.2; 69.7) 

26.5%  
(-26.5; 57.3) 

62.6%  
(9.6; 84.6) 

58 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

         TECHNICAL REPORT 

Table 3A. Relative vaccine effectiveness (95% Confidence Intervals) in 50-64 years against hospitalisation due to COVID-19 of the first, second and third 
booster dose, compared to complete primary vaccination only without booster ≥24 weeks ago for each eight-week overlapping study period between April 
2022 and July 2023, restricting to the six study sites that contributed since the start of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), 
Norway, and Portugal) 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

1 April to 26 May 2022 

1 May to 25 June 2022 

1 June to 26 July 2022 

1 July to 25 August 
2022 

1 August to 25 
September 2022 

1 September to 26 
October 2022 

1 October to 25 
November 2022 

1 November to 26 
December 2022 

1 December 2022 to 25 
January 2023 

1 January to 25 
February 2023 

1 February to 28 March 
2023 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

33.8%  
(-36.6; 67.9) 

55.6% 
 (27; 73) 

39.5%  
(11.8; 58.5) 

35.4%  
(16.2; 50.2) 

31.0% 
 (-0.8; 52.7) 

15.6%  
(-37.5; 48.2) 

9.4% 
 (-46.9; 44.1) 

34.1%  
(0.9; 56.2) 

40.6%  
(7.6; 61.8) 

40.4%  
(-0.5; 64.6) 

19.6%  
(-28.7; 49.8) 

28.6%  
(-55.9; 67.3) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

34.2% 
 (-54.1; 71.9) 

66.6% 
 (62.9; 69.9) 

56.0%  
(29.2; 72.7) 

48.6%  
(20.6; 66.7) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

33.3%  
(-21.3; 63.4) 

32.8%  
(12.5; 48.4) 

28.1%  
(-10.1; 53) 

7.4%  
(-62.7; 47.3) 

8.1%  
(-47.3; 42.6) 

32.0%  
(-17.3; 60.6) 

34.7%  
(-2.3; 58.3) 

31.2%  
(-13.3; 58.2) 

17.5% 
(-32.4; 48.6) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

45.8%  
(-44.2; 79.7) 

65.7%  
(35.1; 81.9) 

70.0%  
(46.6; 83.1) 

29.3%  
(-15; 56.5) 

33.4%  
(-125.4; 80.3) 

57.0% 
 (-24.2; 85.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

63.5%  
(13.6; 84.6) 

32.5%  
(-25.2; 63.6) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

59 

TECHNICAL REPORT

            COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

1 March to 25 April 
2023 

1 April to 26 May 2023 

1 May to 25 June 2023 

1 June to 26 July 2023 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

31.5%  
(-17.3; 60) 

23.8%  
(-35.4; 57.1) 

-12.4%
(-202.9; 58.3) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

27.5%  
(-28.2; 59) 

20.1%  
(-47.7; 56.8) 

-21.1%
(-226.8; 55.1) 

- 

38.6%  
(3.9; 60.7) 

41.9%  
(-9.9; 69.3) 

- 

- 

- 

- 

- 

- 

44.5%  
(9.6; 65.9) 

- 

- 

- 

-66.0%
(-315.4; 33.7) 

32.4%  
(-41.7; 67.8) 

- 

- 

60 

TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 4A. Relative vaccine effectiveness (95% confidence intervals) in ≥80 years against COVID-19 
related mortality of the first, second and third booster dose, compared to complete primary 
vaccination administered ≥24 weeks ago without booster for each eight-week study period, April 
2022 and July 2023, restricting to the six study sites that contributed since the start of the study 
period (Belgium, Denmark, Luxembourg, Navarra (Spain), Norway, and Portugal) 

Complete primary vaccination + first 
booster dose 

Complete primary vaccination + two booster 
doses 

Complete primary vaccination + three booster 
doses 

Overa
ll 

<12 
weeks 

12–24 
weeks 

>24 
weeks 

Overall 

<12 
weeks 

12–24 
weeks 

>24 
weeks 

Overall 

<12 
weeks 

12–24 
weeks 

>24 
weeks 

Study period 

1 April to 26 
May 2022 

1 May to 25 
June 2022 

1 June to 26 
July 2022 

1 July to 25 
August 2022 

1 August to 25 
September 
2022 
1 September to 
26 October 
2022 
1 October to 25 
November 
2022 
1 November to 
26 December 
2022 
1 December 
2022 to 25 
January 2023 
1 January to 25 
February 2023 

1 February to 
28 March 2023 

1 March to 25 
April 2023 

61.3% 
(48.3; 71) 
59.2% 
(23.6; 
78.2) 
53.1% 
(32.2; 
67.5) 
56.5% 
(32.7; 72) 
45.2% 
(15.5; 
64.5) 
37.1% 
(15.2; 
53.4) 
34.6% 
(10.7; 
52.1) 
44.2% 
(24.3; 
58.8) 
38.8% 
(13.7; 
56.6) 
27.9% 
(-14.7; 
54.7) 
38.7% 
(-23.5; 
69.6) 
11.7%  
(-72.8; 
54.9) 

1 April to 26 
May 2023 

46.5%  
(-1; 71.7) 

1 May to 25 
June 2023 

1 June to 26 
July 2023* 

30.3%  
(-15; 
57.8) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

65.0% 
(15.6; 85.5) 

62.2% 
(45.9; 73.6) 

53.7% 
(44.4; 61.5) 

66.0% 
(50.4; 76.7) 

36.5% 
(24.4; 46.6) 

60.3% 
(26.3; 78.6) 

- 

- 

- 

- 

76.0% 
(65.1; 83.5) 

25.2% 
(2.2; 42.8) 

52.9% 
(27.6; 69.3) 

68.0% 
(60.3; 74.2) 

68.0% 
(60; 74.4) 

73.0% 
(54.2; 84.1) 

5.0% 
(-63; 44.6) 

55.8% 
(29.7; 72.3) 

58.1% 
(44.5; 68.3) 

60.3% 
(41.4; 73.1) 

- 

- 

- 

- 

- 

44.6% 
(3.9; 68.1) 

59.9% 
(-29.6; 87.6) 

62.1% 
(-25.7; 88.6) 

33.0% 
(-11.7; 59.8) 

75.1% 
(-109.4; 97) 

82.7% 
(-14.9; 97.4) 

-18.0% 
(-74; 20) 

15.9% 
(-18.8; 40.4) 

73.3% 
(38.2; 88.4) 

85.0% 
(76; 90.6) 

1.0% 
(-44.1; 32) 

22.2% 
(-15.6; 47.7) 

77.0% 
(37.9; 91.5) 

80.0% 
(70.7; 86.3) 

24.0% 
(-12.6; 48.7) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

64.0% 
(48.1; 75) 

62.0% 
(44.7; 73.9) 

58.0% 
(41.6; 69.8) 

58.0% 
(41.1; 70.1) 

- 

- 

- 

- 

- 

- 

- 

- 

26.8% 
(-33.5; 59.8) 

71.2% 
(38.3; 86.6) 

68.0% 
(49.4; 79.8) 

72.0% 
(52; 83.7) 

-42.0% 
(-124; 10) 

38.0% 
(7.1; 58.6) 

42.0% 
(12.2; 61.7) 

30.0% 
(-10.7; 55.7) 

12.5% 
(-58.6; 51.7) 

62.5% 
(37.2; 77.7) 

64.0% 
(31.4; 81.1) 

58.0% 
(22.1; 77.3) 

9.2%  
(-59.1; 48.2) 

38.0% 
(1.7; 60.9) 

40.0% 
(-3.9; 65.4) 

37.0% 
(0.4; 60.2) 

2.0% 
(-52.9; 37.2) 

60.2% 
(34.7; 75.7) 

4.3%  
(-100.8; 54.4) 

50.4%  
(-17.9; 79.2) 

45.1%  
(-3.4; 70.9) 

56.7%  
(13.7; 78.2) 

30.1%  
(-15.8; 57.8) 

30.0%  
(-11.8; 56.2) 

- 

- 

- 

- 

- 

- 

- 

59.3% 
(33.9; 74.9) 

50.0%  
(-91.3; 86.9) 

8.0% 
(-51.6; 44.2) 

54.4%  
(6.6; 77.7 

46.3%  
(-152.5; 88.6) 

30.9%  
(-213.3; 
84.8) 
30.9%  
(-213.3; 
84.8) 

-116.0% 
(-Inf; 99) 

1.0%  
(-88.5; 45.9) 

29.9%  
(-12.3; 56.2) 

16.0%  
(-38.7; 49.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

3.0% 
(-26709.2; 
99.6) 

-129.0%  
(-427.8; 0.7) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

-99.0%
(-364.9; 
14.8)
-7.0%
(-100.4; 
42.9)
14.0%  
(-42.6; 
48.1) 

- 

* Only Norway contributed valid estimates of VE against COVID-19-related death in this period and age group and did not reach 
the 15 events of threshold for pooled results to be reported. 

61 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

TECHNICAL REPORT 

Table 5A. Relative vaccine effectiveness (95% confidence intervals) in 65–79 years against COVID-
19 related mortality of the first, second and third booster dose, compared to complete primary 
vaccination administered ≥24 weeks ago without booster for each eight-week overlapping study 
period, April 2022 and July 2023, restricting to the six study sites that contributed since the start of 
the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), Norway, and Portugal) 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Study period 

1 April to 26 
May 2022 

1 May to 25 
June 2022 

1 June to 26 
July 2022 

1 July to 25 
August 2022 

1 August to 25 
September 
2022 
1 September to 
26 October 
2022 
1 October to 25 
November 
2022 
1 November to 
26 December 
2022 
1 December 
2022 to 25 
January 2023 
1 January to 25 
February 2023 

1 February to 
28 March 2023 

1 March to 25 
April 2023 

1 April to 26 
May 2023 

1 May to 25 
June 2023 

1 June to 26 
July 2023* 

66.0% 
(55.2; 74.3) 

45.8% 
(30.3; 57.9) 

64.0% 
(38.6; 78.9) 

75.4% 
(51.8; 87.5) 

21.5% 
(-355.5; 86.5) 

- 

52.9% 
(9; 75.6) 

52.7% 
(36.7; 64.6) 

45.7% 
(-7.3; 72.5) 

-25.0% 
(-123.1; 30) 

-6.7% (-96; 41. 
9) 

50.4% 
(8.4; 73.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

49.8% 
(-26.6; 80.1) 

27.3% 
(-206.3; 82.8) 

-34.0% 
(-114; 16.1) 

-34.2% 
(-112.6; 15.3) 

61.0% 
(29.3; 78.5) 

61.0% 
(29.3; 78.5) 

28.7% 
(-166.4; 80.9) 

85.3% 
(61.6; 94.4) 

76.0% 
(60.8; 85.3) 

12.4% 
(-61.6; 52.5) 

85.1% 
(73.4; 91.7) 

-88.6% 
(-219.4; -11.4) 

61.2% 
(34.1; 77.2) 

80.0% 
(64.3; 88.8) 

61.7% 
(16.7; 82.4) 

-159.0% 
(-388; -37.4) 

23.0%  
(-60.5; 63.1) 

54.7%  
(-13.4; 81.9) 

60.0%  
(14.9; 81.2) 

37.4% 
(-155.5; 84.7) 

53.1%  
(-1.3; 78.3) 

61.8%  
(29.3; 79.4) 

39.0%  
(-23; 69.8) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

41.5% 
(-9; 68.7) 

15.0% 
(-72.5; 58.1) 

68.7%  
(-0.9; 90.3) 

62.4%  
(27.9; 80.4) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

30.0%  
(-82.7; 73.2) 

60.9%  
(19.6; 81) 

37.0%  
(-27; 68.8) 

- 

47.5% 
(-37.9; 80) 

27.2% 
(-215.3; 83.2) 

-33.0% 
(-111.8; 16.5) 

-8.5% 
(-69.6; 30.6) 

40.2% 
(-48.8; 76) 

33.0% 
(-1.7; 55.9) 

-7.5% 
(-80; 35.8) 

-82.6% 
(-661.9; 56.2) 

42.7%  
(-16.2; 71.7) 

57.7%  
(-7.8; 83.4) 

62.0%  
(19.4; 82.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

-110.0% 
(-282.7; -15.2) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

* No study site contributed valid estimates of VE against COVID-19-related death in this period and age group. 

62 

 
 
 
 
 
 
TECHNICAL REPORT 

COVID-19 VE against hospitalisation and death using EHR in eight European countries: first update 

Table 6A. Relative vaccine effectiveness (95% confidence intervals) in 50–64 years against COVID-
19 related mortality of the first, second and third booster dose, compared to complete primary 
vaccination administered ≥24 weeks ago without booster in 50–64 years for each eight-week 
overlapping study period, April 2022 and July 2023, restricting to the six study sites that contributed 
since the start of the study period (Belgium, Denmark, Luxembourg, Navarra (Spain), Norway, and 
Portugal) 

Complete primary vaccination + first booster dose 

Complete primary vaccination + two booster doses 

Study period 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

Overall 

<12 weeks 

12–24 weeks 

>24 weeks 

1 April to 26 
May 2022 

73.8% 
(-31.6; 94.8) 

1 May to 25 
June 2022 

1 June to 26 
July 2022 

1 July to 25 
August 2022 

1 August to 25 
September 
2022 
1 September to 
26 October 
2022 
1 October to 25 
November 
2022 
1 November to 
26 December 
2022 
1 December 
2022 to 25 
January 2023 
1 January to 25 
February 2023 

1 February to 
28 March 2023* 

1 March to 25 
April 2023* 

1 April to 26 
May 2023* 

1 May to 25 
June 2023* 

1 June to 26 
July 2023* 

3.2% 
(-387.9; 80.8) 

- 

48.8% 
(-7.9; 75.7) 

-14.8% 
(-588.8; 80.9) 

31.8% 
(-137.1; 80.4) 

16.0% 
(-206; 76.9) 

-12.0% 
(-148.9; 49.6) 

27.5% 
(-100.7; 73.8) 

-9.2% 
(-173.6; 56.4) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

48.0% 
(-11.2; 75.7) 

-17.6% 
(-637.1; 81.2) 

30.0% 
(-153.4; 80.7) 

5.6% 
(-324.4; 79) 

- 

- 

- 

- 

- 

- 

- 

-32.9% 
(-245.3; 48.8) 

34.6% 
(-74; 75.5) 

7.4% 
(-325.7; 79.9) 

-73.1% 
(-368.8; 36.1) 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

* No study site contributed valid estimates of VE against COVID-19-related death in this period and age group. 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

63 

European Centre for Disease 
Prevention and Control (ECDC)

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