Effectiveness of BNT162b2 Vaccine Booster Against SARS-CoV-2 Infection and Breakthrough Complications, Israel

Aharona Glatman-Freedman; Michal Bromberg; Yael Hershkovitz; Hanna Sefty; Zalman Kaufman; Rita Dichtiar; Lital Keinan-Boker


Emerging Infectious Diseases. 2022;28(5):948-956. 

In This Article


Our results demonstrate that, after the BNT16b2 booster dose, VE against SARS-CoV-2 infection reached levels that were observed shortly after the second vaccine dose.[6] VE point estimates of >90% were observed in week 2 in persons 16–59 years of age and in week 3 in persons ≥60 years of age. Similar delay in achieving high VE among elderly persons was also shown after the second BNT162b2 vaccine dose.[6] Highest-level VE was maintained for up to 11 weeks, as shown in persons ≥60 years of age included in our study. The decline in VE that occurred afterward was initially mild, still maintaining VE point estimates ≥90% for up to week 17 of the evaluation period in persons ≥60 years of age. The decline in VE became steeper during the last 2 weeks of the evaluation period.

The B.1.617.2 (Delta) variant was the most prevalent variant in Israel through November 2021. However, the last 2 evaluation weeks, which occurred in December 2021 (Appendix Table 2), coincided with the beginning of a new wave of illness and the sharp rise in the B.1.1.529 (Omicron) variant in Israel. Waning immunity was shown several months after the second BNT162b2 vaccine dose[2,3,10] and was temporarily associated with the rise of the B.1.617.2 (Delta) variant in Israel. However, a fresh 2-dose BNT162b2 vaccination regimen was found to be highly effective against the B.1.617.2 (Delta) variant.[1]

Early evaluations suggest that VE of 2 doses of the BNT162b2 against B.1.1.529 (Omicron) variant–related infection, symptomatic disease, and hospitalizations was reduced compared with VE against the B.1.617.2 (Delta) variant (;[11,12] C.H. Hansen et al., unpub. data, https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v3; N. Andrews et al., unpub. data, https://www.medrxiv.org/content/10.1101/2021.12.14.21267615v1). VE of the BNT162b2 booster dose against infection and symptomatic disease caused by the B.1.1.529 (Omicron) variant was also lower than for the B.1.617.2 (Delta) variant (;[11] C.H. Hansen et al., unpub. data; N. Andrews et al., unpub. data). The difference in VE against the B.1.1.529 (Omicron) and B.1.617.2 (Delta) variants increased as time passed from booster dose administration.[11] Therefore, the steeper decrease in the 3-dose VE in the last 2 weeks of our study period could be caused, at least in part, by the rapid spread of the B.1.1.529 (Omicron) variant in Israel.

Several studies have evaluated the shorter-term effect of the BNT162b2 booster dose on SARS-CoV-2 infection and complications (;[13–17] N. Andrews et al., unpub. data, https://www.medrxiv.org/content/10.1101/2021.11.15.21266341v1) and found that a high degree of protection was achieved. Some of these studies used booster-eligible 2-dose vaccine recipients as controls,[13–15,17] but our study evaluated VE by using unvaccinated persons as controls. Booster dose VE analysis using unvaccinated persons as controls is paramount, because the baseline VE against SARS-CoV-2 for booster dose recipient is >0%, and time to eligibility for a booster dose might vary among countries. Furthermore, our analysis shows the magnitude of protection offered by the booster dose in a manner that enables easy comparison with other VE studies.

Analyzing the reduction in complications among SARS-CoV-2 vaccine recipients is crucial for public health policy. Our results demonstrated substantial protection from complications among booster-dose vaccine recipients throughout the evaluation period and, further, suggest that this protection may be higher than the protection found shortly after the receipt of the second dose.[6] Although a study from a health maintenance organization in Israel demonstrated VE estimates of 93% against hospitalizations, 92% against severe disease, and 81% against death,[15] such analysis cannot distinguish between complications averted because of reductions in SARS-CoV-2 infections and reduction of complications among breakthrough cases. Further analysis is necessary to determine whether rate reductions of complications in booster-dose recipients are affected by the spread of the B.1.1.529 (Omicron) variant and whether those rate reductions are waning over time.

Our study's first limitation is that the size of the unvaccinated control study group was calculated on the basis of Israel Central Bureau of Statistics data. Nevertheless, these data included population size by sex and age, which enables statistical adjustment. Furthermore, data concerning hospitalizations, disease severity, and deaths were available in the SARS-CoV-2 PCR test repository for unvaccinated SARS-CoV-2–positive persons. The lack of information regarding the presence of comorbidities constitutes another limitation. However, the use of multiple cohorts, the size of the population included in our study, the consistent VE estimates among various age groups, and the successful use of similar methodology in previous SARS-CoV-2 VE studies[1,6] support the validity of our results.

In this evaluation, we did not estimate VE against symptomatic disease. When the number of PCR-positive persons increases, the ability to conduct epidemiologic investigation and determine whether symptoms were present greatly diminishes. A further limitation was the low number of weekly complications in SARS-CoV-2–positive persons, particularly in weeks of lower SARS-CoV-2 circulation.(Table 1, Table 2 and Table 3). However, this limitation was less evident among persons ≥60 years of age, for whom the number of weekly complications is higher than for persons 16–59 years of age.

SARS-CoV-2 PCR testing and vaccination practices could vary among persons. Such differences can stem from behavior, occupation (such as being a healthcare worker), or health factors (such as having symptoms or risk factors or residing in a nursing home) and can potentially affect VE estimates against infection. Because SARS-CoV-2 PCR testing has been commonly performed among hospitalized patients, determination of reductions in hospitalizations, severe or critical disease, and death rate were probably not affected by factors that might affect testing practices of nonhospitalized patients.

No distinction was available in the MOH SARS-CoV-2 data repository between persons who were hospitalized because of COVID-19 and those who were hospitalized because of other reasons and were SARS-CoV-2–positive. However, the severity status that is registered in the repository is given to COVID-19 patients on the basis of National Institutes of Health guidelines.[7]

In conclusion, our results showing high VE of the BNT162b2 booster dose against SARS-CoV-2 cases and the maintenance of positive effects among breakthrough cases demonstrate the duration of the booster-dose effect during a period in which the Delta variant was predominant. However, the reduced VE in an Omicron-variant setting indicates that additional tools are required to combat new variants of concern.