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Review 2: "Protection Across Age Groups of BNT162b2 Vaccine Booster against Covid-19"

This paper claims that compared to people who only received two doses of the Pfizer vaccine, those who additionally received the booster dose are less likely to have SARS CoV 2 infection, severe illness, and death. Both reviewers agree on the robustness of the study methods.

Published onNov 06, 2021
Review 2: "Protection Across Age Groups of BNT162b2 Vaccine Booster against Covid-19"
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key-enterThis Pub is a Review of
Protection Across Age Groups of BNT162b2 Vaccine Booster against Covid-19

AbstractBACKGROUNDFollowing administration to persons 60+ years of age, the booster vaccination campaign in Israel was gradually expanded to younger age groups who received a second dose >5 months earlier. We study the booster effect on COVID-19 outcomes.METHODSWe extracted data for the period July 30, 2021 to October 6, 2021 from the Israeli Ministry of Health database regarding 4,621,836 persons. We compared confirmed Covid-19 infections, severe illness, and death of those who received a booster ≥12 days earlier (booster group) with a nonbooster group. In a secondary analysis, we compared the rates 3-7 days with ≥12 days after receiving the booster dose. We used Poisson regressions to estimate rate ratios after adjusting for possible confounding factors.RESULTSConfirmed infection rates were ≈10-fold lower in the booster versus nonbooster group (ranging 8.8-17.6 across five age groups) and 4.8-11.2 fold lower in the secondary analysis. Severe illness rates in the primary and secondary analysis were 18.7-fold (95% CI, 15.7-22.4) and 6.5-fold (95% CI, 5.1-8.3) lower for ages 60+, and 22.0-fold (95% CI, 10.3-47.0) and 3.2-fold (95% CI, 1.1-9.6) lower for ages 40-60. For ages 60+, COVID-19 associated death rates were 14.7-fold (95% CI, 9.4-23.1) lower in the primary analysis and 4.8-fold (95% CI, 2.8-8.2) lower in the secondary analysis.CONCLUSIONSAcross all age groups, rates of confirmed infection and severe illness were substantially lower among those who received a booster dose of the BNT162b2 vaccine.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



Bar-On et al. have published an updated follow-up study to their recent NEJM paper (N Engl J Med. 2021 Oct 7;385(15):1393-1400). The researchers analyzed the effect of booster vaccination (three doses) versus two doses with BNT162b2 (Pfizer) in people +60 years of age and younger age groups in Israel. The methods are robust, and they perform sensitivity analysis, thus confirming their claims. The authors prove that booster vaccination with BNT162b2 confers improved protection against infection for at least two months post-booster date. The effect was sustained in all age groups. The manuscript also claims reductions in severe disease; however, the frequency of severe disease was low, making their conclusions on disease severity slightly less robust. Lastly, they could not assess mortality because of very low numbers (a win of vaccination, boosted or not!). There has been criticism regarding the definition of severe disease in Israel. Since severity is defined freely by front-line providers and because WHO’s definitions changed during the pandemic (decreasing oxygen requirements from 93% to 90% to be considered severe), the data on severity may have more bias than the data on infections. The implications of this study are debatable (not because of the quality of the paper, but because implications depend on resource availability, ethics, and overall intent of a country’s public health response). Some will see this paper as supporting evidence for widespread utilization of boosters, while others may want to see longer-term data and more data on safety. It is likely unquestionable that boosters decrease the likelihood of infection. However, the long-term durability of the added protection against infection is not evident yet and may well be temporary. The effects on severity and mortality are likely lower, especially in younger fully vaccinated age groups. All in all, this is a critical study that deserves publication after peer-review. This manuscript will inform policy, but policy, as always, should and will consider other factors such as vaccine availability and global supply and coherence with other local and global public health measures implemented. 

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