Third dose of BNT162b2 COVID-19 vaccine effective at decreasing risk of hospitalization [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. Compared to two doses of the BNT162b2 vaccine, a third booster dose was estimated to be 93% effective against admission to hospital due to COVID-19 infection.

2. A third dose was also associated less severe disease and lower COVID-19 related mortality.

Original Date of Publication: December 2021

Study Rundown: Despite a rigorous vaccination campaign in Israel, the country is still reporting vaccine “breakthrough” cases of COVID-19 infection. Israel, which has already rolled out many third doses of BNT162b2 mRNA vaccine, may be used as a pseudo-trial population to evaluate third dose vaccine effectiveness. This was the goal of this study, which compared individuals who had received a third dose at least 5 months after their second dose. Using demographically matched controls with only two doses, effectiveness of preventing hospitalization, severe disease and death was measured. This study found that a third dose of the BNT162b2 was highly effective at preventing hospitalization compared to two doses. Three doses were also more effective at preventing severe disease and death from COVID-19. Efficacy from a third dose was most pronounced in individuals over the age of 40. Limitations included lack of individual data for patients under 40. Nonetheless, this study provides key information which will help inform national vaccination strategies moving forward.

Click to read the study in Lancet

In-Depth [retrospective cohort]: This retrospective study utilized the highly vaccinated Israeli population to investigate the effectiveness of a third dose of the mRNA BNT162b2 (Pfizer-BioNTech) vaccine. The eligible population included individuals who had received two doses at least 5 months prior to their third dose. A matched control group included individuals matched to the treatment group by age, sex, place of residence, and risk factors for severe COVID-19 infection, but had only received two doses total. There were 728 321 matched pairs, of whom 51% were female and had a median age of 52 years. A total of 198 476 individuals were matched to themselves before and after third dose. Outcomes included risk of admission to hospital, severe disease, and death from COVID-19 infection. Outcomes were recorded 7 days after the third dosage was received and continued for a median follow-up of 13 days. Compared to two doses, a third dose conferred an effectiveness of 93% against hospital admission, 92% against severe disease and 81% against death from COVID-19.Effectiveness was found to be similar regardless of gender. The effectiveness of the third dose was to be greater in participants aged 40-69 years and >70 years, compared to those aged 16-39.

Barda N, Dagan N, Cohen C, Hernán MA, Lipsitch M, Kohane IS, et al. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. The Lancet. 2021 Dec 4;398(10316):2093–100.

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