Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study
Open accessAbstract
Background 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.Methods 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.Findings 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.Interpretation 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.Funding The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.
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Administering a third dose of COVID-19 mRNA vaccine as a booster has enabled a substantial increase in GMT against WT, Delta and Omicron variants.
“Administering a third dose of COVID-19 mRNA vaccine as a booster has enabled a substantial increase in GMT against WT, Delta and Omicron variants 16 .”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [16]
The Introduction (page not available) reports a pronounced humoral response after a third BNT162b2 dose. It does not report geometric mean titres (GMT) or an increase measured against WT, Delta, and Omicron; the study evaluates severe clinical outcomes instead. (LLM, conf=0.82)
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- Authors
- Barda, N., Dagan, N., Cohen, C., Hernán, M. A., Lipsitch, M., Kohane, I. S., Reis, B. Y., & Balicer, R. D.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Bar-Ilan University (IL)
- Harvard University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Balicer, Ran D
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 398
- Issue
- 10316
- Pages
- 2093-2100
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC8555967
- OpenAlex
- W3210126657
- Cited by
- 860
- References
- 22
- Citations by year
- 2026: 15 · 2025: 42 · 2024: 123 · 2023: 190 · 2022: 440 · 2021: 50
- FWCI
- 63.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Clalit Health Services
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- COVID-19 pandemic, BNT162b2 mRNA vaccine, third dose, booster vaccination, vaccine effectiveness, severe COVID-19 outcomes, hospitalization, COVID-19 mortality, Delta variant, waning immunity, Israel, Clalit Health Services
- MeSH terms
- COVID-19, SARS-CoV-2, Vaccine Efficacy, BNT162 Vaccine, Adult, Aged, Female, Humans, Immunization, Secondary, Israel, Male, Middle Aged, Prognosis, Mass Vaccination, Pandemics
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