Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study

Abstract

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.

Keywords: COVID-19; Effectiveness; Elderly population, Italy; SARS-CoV-2; mRNA vaccines.

Fig. 1

Epidemic curve of notified cases of SARS-CoV-2 infections alongside estimates of the Omicron subvariants prevalence at different calendar weeks.

Fig. 2

Selection of the individuals included in the study. ¹ Starting date of the 1st booster vaccination campaign for persons ≥ 80 years, regardless of frailty status and other high-risk conditions. ² Not eligible to receive a second booster dose of vaccine on 11 April 2022 (starting date of the study). ³ Matching by sex, exact age (up to 95 and then grouping ≥ 95 years), country of birth (Italy vs other countries), region where vaccination took place (19 regions and 2 autonomous provinces), presence/absence of high-risk conditions (i.e., residence in LTCF residents or at least one of the health-risk conditions listed in Table S1 of the supplementary appendix), time from prior infection (i.e., no infection, exact number of days up to 365, and then grouping > 365 days), week of administration of the 1st booster dose, type of the 1st booster vaccine dose (i.e., BNT16b2 or mRNA-1273).

Fig. 3

Cumulative incidence of SARS-CoV-2 infection and severe COVID-19 by booster group. Shaded areas indicate the 95% confidence intervals.

Fig. 4

Relative hazard reduction of SARS-CoV-2 infection and severe COVID-19 at different time intervals after the administration of a second booster vaccine dose (sensitivity analysis).