Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe



Many countries are experiencing a resurgence of COVID-19, driven predominantly by the delta (B.1.617.2) variant of SARS-CoV-2. In response, these countries are considering the administration of a third dose of mRNA COVID-19 vaccine as a booster dose to address potential waning immunity over time and reduced effectiveness against the delta variant. We aimed to use the data repositories of Israel’s largest health-care organisation to evaluate the effectiveness of a third dose of the BNT162b2 mRNA vaccine for preventing severe COVID-19 outcomes.


Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose. Eligible participants had received the second vaccine dose at least 5 months before the recruitment date, had no previous documented SARS-CoV-2 infection, and had no contact with the health-care system in the 3 days before recruitment. Individuals who are health-care workers, live in long-term care facilities, or are medically confined to their homes were excluded. Primary outcomes were COVID-19-related admission to hospital, severe disease, and COVID-19-related death. The third dose effectiveness for each outcome was estimated as 1 – risk ratio using the Kaplan-Meier estimator.


1 158 269 individuals were eligible to be included in the third dose group. Following matching, the third dose and control groups each included 728 321 individuals. Participants had a median age of 52 years (IQR 37–68) and 51% were female. The median follow-up time was 13 days (IQR 6–21) in both groups. Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death.


Our findings suggest that a third dose of the BNT162b2 mRNA vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least 5 months ago.


The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.


Despite the initially promising results of nationwide vaccination campaigns, many countries are currently experiencing a resurgence of COVID-19, dominated by the delta (B.1.617.2) variant of SARS-CoV-2. After several months of low pandemic activity in early 2021, Israel is experiencing its fourth pandemic wave, despite over 55% of the population having been vaccinated with two doses of the BNT162b2 mRNA COVID-19 vaccine. First and second doses were given 21 days apart, as per the pre-approval randomised trials. The increase in infections and hospitalisations of vaccinated individuals likely stems from a combination of waning vaccine immunity over time,

  • Zipeto D
  • Carbonare LD
  • Valenti MT
  • et al.
Antibody response to BTN162b2 mRNA vaccination in naïve versus SARS-CoV-2 infected subjects with and without waning immunity.