Interim analysis of COVID-19 vaccine effectiveness against hospitalisation and death using electronic health records in six European countries

A retrospective cohort was constructed from linked electronic health records (EHR) in each country. Country- specific (level) relative VE (rVE) was estimated on a monthly basis, using a study period covering an eight-week follow-up period. Each month the study period was shifted forward to the following month. Country estimates were then pooled together. The study period covered in this report is April 2022 to March 2023. The rVE of first, second and third booster doses was estimated and compared to the VE of complete primary vaccination received at least 24 weeks ago (≥24 weeks).

Between April 2022 and March 2023, the number of individuals included in the analysis in each study period varied between 0.5 million and 1.3 million individuals with complete primary vaccination series ≥24 weeks ago but without a booster, between 3.1 million and 13.2 million individuals completely vaccinated with a first booster, between no individuals and 6.8 million individuals completely vaccinated with a second booster and between no individuals and 0.7 million completely vaccinated with a third booster. About 31 900 hospitalisations due to COVID- 19 and 13 100 COVID-19-related deaths were recorded across the different sites throughout the study period.

The highest number of person-months contributing to the analysis was observed for Belgium and Portugal, followed by Norway, Denmark, Navarre (Spain), and Luxembourg. In persons aged ≥80 years, Belgium and Portugal rolled out the second booster dose over spring 2022 and the third booster dose in autumn 2022, while the administration of a second booster began in autumn 2022 in the remaining participating countries.

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 years (Figure 2). A second booster dose was administrated initially in persons aged ≥80 years from July 2022 onwards in most participating countries except for Belgium and Portugal, where it started earlier in spring 2022 in those aged ≥80 followed by 50–79year olds in autumn 2022. In these two countries, the third booster dose was then deployed in ≥80-year-olds in October–November 2022.

Compared to complete primary vaccination, the first booster dose rVE against hospitalisation due to COVID-19 was mostly ≤50% between April 2022 and March 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 February and March 2023, the first booster (mostly administered >24 weeks) showed little to no added protection: rVE estimates ranged between -13–17%, 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 76–79% against hospitalisation due to COVID-19 and to 76–85% against COVID-19 related death. Relative vaccine effectiveness also waned with time, falling to ≤50% after 24 weeks. In the most recent estimate, between February and March 2023, rVE of the second booster ranged between 33–49% against hospitalisation and 50–63% against mortality 12–24 weeks after administration and between 3.5–43% against hospitalisation and 50% against mortality (estimated only in ≥80 year olds) after 24 weeks.

Compared to complete primary vaccination, rVE of the third booster could only be estimated in individuals aged

≥80 years in Portugal and Belgium. Relative vaccine effectiveness against hospitalisation due to COVID-19 was 72% shortly after administration but waned rapidly, being zero 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). Relative vaccine effectiveness against mortality was 64% initially (<12 weeks after administration) and waned rapidly thereafter (<50% 12–24 weeks after administration with large confidence intervals). In February–March 2023, the rVE of a third booster 12–24 weeks after administration was 3% (95% CI: -26 709; 100).

Overall, results indicated that booster doses restored protection shortly after administration, but it waned in the period up to 24 weeks after administration.

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.