Protection of BNT162b2 Vaccine Booster Against COVID-19 in Israel

Quick Takes

  • This is an observational study leveraging a nationwide database including 1,137,804 persons aged ≥60 years who received at least two doses of the BNT162b2 vaccines, in a country where the third booster dose was approved.
  • The rate of confirmed SARS-CoV-2 infections and severe COVID-19 was significantly lower in persons who received the booster vaccine compared to those who did not by a factor of 10 and 20, respectively.
  • There are some concerns for unaccounted confounders in the study, warranting more in-depth study of the relative effectiveness of a booster dose prior to recommending a mass roll-out of a booster dose.

Study Questions:

Is a third booster dose of the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer–BioNTech) associated with a lower rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?


The authors leveraged the Israeli Ministry of Health database and identified a cohort of 1,137,804 persons who were ≥60 years of age and had been fully vaccinated (i.e., had received two doses of BNT162b2). In the primary analysis, the authors compared the rate of SARS-CoV-2 infection and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). The primary analysis was adjusted for person-days at risk given participants could have contributed days to both booster and nonbooster groups. Poisson regression was used to adjust for the following covariates: age, sex, demographic group, and the date of the second vaccine dose. Several sensitivity analyses were performed to test the robustness of the findings, including using alternative statistical methods, examining specific study periods, and stratifying according to demographic group.


The booster group, as compared with the nonbooster group, had more men (49% vs. 42%), more participants from the general Jewish population (92% vs. 81%), and more participants who were ≥70 years of age (58% vs. 46%). The nonbooster group included approximately 5.2 million person-days (4.6 million for the analysis of severe illness), with 4,439 confirmed infections and 294 cases of severe illness. The booster group included approximately 10.6 million person-days (6.3 million for the analysis of severe illness), with 934 confirmed infections and 29 cases of severe illness. The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4-12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9-29.5). Sensitivity analyses supported the primary findings.


In this retrospective observational study, the rates of confirmed COVID-19 and severe illness were lower among those aged ≥60 years who received a booster (third) dose of the BNT162b2 vaccine.


This observational study, using a nationwide database of a population with high rates of vaccination for SARS-CoV-2 and in whom a booster dose is being provided, provides encouraging data on the effectiveness of the strategy. This strategy is increasingly being considered due to concerns of waning vaccine effectiveness. Confounding remains a major concern and is apparent in this study given a reduction in rate of confirmed infection is seen already at day 1 post-booster vaccination, suggesting that there are differences between the booster and nonbooster groups that may have not been accounted for. Accordingly, the factor reduction in rate of infection may have been overestimated in this study. Important considerations, which were not a focus of this study, are clinical characteristics and timing of the third booster dose. Certain population subgroups will more likely derive benefit from a third dose than others. Recent evidence suggests that the BNT162b2 vaccine remains over 80% efficacious at 6 months post-second dose, and the booster dose is thus far recommended for immunosuppressed individuals. Justifying a mass rollout of a third dose requires more rigorous evidence to define timing and population selection.

Clinical Topics: COVID-19 Hub, Geriatric Cardiology, Prevention

Keywords: Aged, Critical Illness, Coronavirus, COVID-19, Israel, Primary Prevention, RNA, Messenger, SARS-CoV-2, Vaccination, Vaccines

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