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

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.