The strongest evidence to date demonstrating the effectiveness of a third dose of mRNA Covid-19 vaccine comes from an observational study from Israel which reported 93% effectiveness for admission to hospital, 92% for severe disease and 81% for Covid-19 related deaths when compared to those who had received 2 doses of the vaccine (Pfizer, BNT162b2 mRNA) at least 5 months before.¹

This was a large population-based study involving over a million people 16 years or older (one-half in each group) who were eligible for the third dose (median age 52 y); those living in long-term facilities, healthcare workers and those medically confined to their homes were excluded. Vaccine effectiveness was evaluated at least 7 days after receipt of the third dose.  Median follow-up period was 13 days for both groups.

Overall effectiveness of the third dose vs 2 vaccine doses was 93% (88-97) for admission to hospital, 92% (82-97) for severe disease and 81% for death (59-97). Effectiveness of the third dose was similar between males and females and between individuals 40-60 years and those at least 70 years of age; effectiveness could not be determined in the younger age group due to small number of adverse outcomes.

What makes this study stand out among the previous works^2,3 is that it controlled for important possible confounders, including sociodemographic factors, clinical factors, and behavioral factors related to Covid-19.  Limitations include its observational nature and exclusion of certain at risk groups, such as nursing home residents and healthcare workers.

Given the increasing number of Covid-19 cases in many communities at this writing, the news that a booster shot of an mRNA vaccine provides further protection in preventing Covid-19 is very welcome!

Bonus Pearl: Did you know that in a study measuring the immune response after the third dose of an mRNA vaccine (Moderna) in those 60 years of age or older, the median antibody titer rose 50-fold!⁴

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References

1. Barda N, Dagan N, Cohen C, et al. Effectiveness of a third dose of the BNT162b2 mRNA Covid-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet, published online October 29, 2021. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2902249-2
2. Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 vaccine.N Engl J Med 2021; published online Sept 15, https://doi.org/10.1056/nejmoa21114255.
3. Patalon T, Gazit S, Pitzer VE, et al. Short term reduction in the odds of testing positive for SARS-CoV-2; a comparison between two doses and three doses of the BNT162b2 vaccine. medRxive 2021;published online Aug 31. https://doi.org/10.1101/2021.008.29.21262792 (preprint).
4.  Eliakim-Raz N, Liebovici-Weisman Y, Stemmer A, et al. Antibody titers before and aftera third dose of SARS-CoV-2 BNT162b2 vaccine in adults ages ≥60 years. JAMA. Published online November 5, 2021. doi:10.1001/jama.2021.19885 https://jamanetwork.com/journals/jama/fullarticle/2786096

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