Results of the largest real-world study of third dose of COVID-19 vaccine effectiveness released
[Oct 30, 2021: CLALIT RESEARCH INSTITUTE]
A quiet research revolution has occurred in our understanding of the biology of ageing. (CREDIT: Creative Commons)
Many countries are currently experiencing a resurgence of SARS-CoV-2 infections despite hitherto successful vaccination campaigns. This may be due to the greater infectiousness of the delta (B.1.617.2) variant of SARS-CoV-2, and to waning immunity of vaccines administered months earlier. In the face of the current resurgence, several countries are planning to administer a third booster dose of mRNA COVID-19 vaccine.
This study suggests that a third vaccine dose is effective in reducing severe COVID-19-related outcomes compared to individuals who have received two vaccine doses at least 5 months ago. It 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 behavioral factors. The study’s large size also allows a more precise assessment of the vaccine’s effectiveness across different time periods, different subpopulations (by sex, age and number of comorbidities), and different severe outcomes (which are rarer and thus require greater sample size). A recent clinical trial conducted by BioNTech included a smaller sample size and did not estimate the third-dose’s effects for more severe outcomes.
The study took place from July 30, 2021 through Sept 23, 2021, coinciding with Israel’s fourth wave of coronavirus infection and illness, during which the Delta (B.1.617.2) variant was the dominant strain in the country for new infections (with very few exceptions).
Researchers reviewed data from 728,321 individuals aged 12 or above who had received the third dose of the BNT162b2 vaccine. These individuals were carefully matched 1:1 with 728,321 individuals who had received only two shots of the BNT162b2 vaccine at least five months prior. The matching was based on an extensive set of demographic, geographic and health-related attributes associated with risk of infection, risk of severe disease, health status and health seeking behavior. Individuals were assigned to each group dynamically based on their changing vaccination status (198,476 individuals moved from the unvaccinated cohort into the vaccinated cohort during the study). Multiple analyses were conducted to ensure that the estimated vaccine effectiveness was robust to potential biases. The study included a total of over 12,000,000 person-days of follow-up.
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The results show that, compared with individuals who received only two doses five months prior, individuals who received three doses of the vaccine (7 days or more after the third dose) had 93% lower risk of COVID-19-related hospitalization, 92% lower risk of severe COVID-19 disease, and 81% lower risk of COVID-19-related death. Vaccine effectiveness was found to be similar for different sexes, age groups (ages 40-69 and 70+) and number of comorbidities.
The study also included a population-level analysis which found that infection rates began to drop for each age group 7-10 days after that age group became eligible for the third dose.
The research was conducted by Dr. Noam Barda, Dr. Noa Dagan, Prof. Cyrille Cohen, and Prof. Ran Balicer from the Clalit Research Institute, as well as Prof. Miguel Hernán and Prof. Marc Lipsitch of the Harvard T.H. Chan School of Public Health, Professor Isaac S. Kohane of Harvard Medical School, and Prof. Ben Reis of Boston Children’s Hospital and Harvard Medical School.