Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe
Summary
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.
Introduction
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given that many people in Israel were vaccinated 5–7 months ago, and from potentially reduced effectiveness of the vaccine against the delta variant.
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the Israeli Ministry of Health announced a campaign to administer a third dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer–BioNTech). This campaign began with immunocompromised patients on July 13, 2021, and was expanded several times to include people aged over 60 years (on July 30), 50 years (on Aug 12), 40 years (on Aug 19), 30 years (on Aug 24), and eventually the entire population over the age of 12 years on Aug 30. The third dose was only given to people who had received the second dose at least 5 months ago. Administration of the third dose progressed rapidly, reaching over half of the population aged at least 60 years within the first 2 weeks. Other countries such as the USA, the UK, Germany, and France are planning or conducting campaigns to provide an additional dose for elderly and vulnerable populations,
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such as immunocompromised patients, who have been shown to mount a lesser immune response to the vaccine.
On Aug 12, 2021, the US Food and Drug Administration amended the authorisations for both mRNA COVID-19 vaccines (Pfizer–BioNTech’s BNT162b2 and Moderna’s mRNA-1273) to allow for the use of an additional dose in immunocompromised patients.
On Sept 22, 2021, the authorisation was extended to include individuals aged 65 years or older, and younger individuals with increased medical or occupational risk.
Evidence before this study
No formal literature review was done. Several previous publications regarding the effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine have focused on antibody response, showing a pronounced humoral response after administration of the booster. Two recent studies from Israel have focused on clinical outcomes. The first reported a reduction of 90–96% in the risk for severe disease starting from day 12 after the booster dose, but did not adjust for pre-existing clinical conditions related to the risk of severe disease and did not evaluate the effectiveness within subgroups. The second found a reduction of 70–84% in the probability of testing positive for SARS-CoV-2 among vaccinated individuals, but did not estimate effectiveness for more severe outcomes.
Added value of this study
To our knowledge, the present study is the first to estimate the effectiveness of a third dose of an mRNA COVID-19 vaccine—BNT162b2 specifically—against severe outcomes with adjustment for various possible confounders, including comorbidities and behavioural factors, and within subgroups. Our results suggest that that a third dose of the BNT162b2 vaccine is effective in preventing severe COVID-19-related outcomes. Compared with two doses of the vaccine administered at least 5 months ago, receiving a third dose was estimated to have an effectiveness of 93% in preventing COVID-19-related admission to hospital, 92% in preventing severe disease, and 81% in preventing COVID-19-related death.
Implications of all the available evidence
As of October, 2021, many countries are experiencing a resurgence of SARS-CoV-2 infections despite hitherto successful vaccination campaigns. This situation has been suggested to be caused by the greater infectiousness of the delta (B.1.617.2) variant of SARS-CoV-2, and by waning immunity as time passes from earlier vaccination. In the face of the current resurgence, several countries are planning to administer a third booster dose of mRNA COVID-19 vaccine. Our study suggests that a third vaccine dose is effective in reducing severe COVID-19-related outcomes for patients who have received two vaccine doses at least 5 months ago.
We aimed to use the data repositories of Israel’s largest health-care organisation to estimate the effectiveness of a third dose of the BNT162b2 COVID-19 vaccine in preventing severe…
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