BNT162b2 vaccine booster protection against Covid-19 in Israel

Population Study

population study.

Study participants included subjects 60 years of age or older who had been fully vaccinated before 1 March 2021, had sex data available, and had no documented positive SARS-CoV-2 PCR test result before 30 July 2021, They did not return from overseas travel in August 2021. The number of confirmed infections in each group is shown in parentheses.

Our analysis was based on medical data from the Ministry of Health database extracted on September 2, 2021. At that time, a total of 1,186,779 Israeli residents aged 60 or older (i.e., received two doses) of BNT162b2) had been vaccinated before 5 at least two months (i.e., before March 1, 2021) and were alive on July 30, 2021. We excluded from the analysis participants who had missing data regarding sex; They were abroad in August 2021; Diagnosed with PCR-positive Covid-19 before July 30, 2021; received a booster dose before July 30, 2021; or were fully vaccinated before January 16, 2021. A total of 1,137804 participants met the inclusion criteria for analysis (shape 1).

Data included vaccination dates (first, second, and third doses). Information regarding the PCR test (sampling dates and results); History of any hospitalization for Covid-19 (if relevant); Demographic variables, such as age, gender, and demographic group (general Jewish, Arab, or ultra-Orthodox population), as determined by the participant’s statistical area of ​​residence (similar to a census block)8; and clinical status (mild or severe illness). Severe illness was defined as a resting respiratory rate of more than 30 breaths per minute, an oxygen saturation of less than 94% while breathing ambient air, or a ratio of the arterial partial pressure of arterial oxygen to the portion of inspiratory oxygen of less than 300.9

study design

Our study period began at the start of the booster vaccination campaign on 30 July 2021. End dates were chosen as August 31, 2021 for confirmed infection and August 26, 2021 for severe disease. The selection of dates is designed to minimize the effects of missing outcome data due to delays in reporting test results and severe disease progression. The protection gained by the booster shot was not expected to reach its maximum potential immediately after vaccination, but rather builds up over the following week.10,11 At the same time, during the first days after vaccination, significant behavioral changes are possible in the population vaccinated with the booster vaccine (Figure S1 in the Supplementary Appendix, available with the full text of this article at One such potential change is to increase avoidance of excess risk until the booster dose is effective. Another potential change is the lower rate of Covid-19 testing around the time the booster is received (Figure S2). Thus, it is best to evaluate the effect of the booster only after a sufficient period has passed since its administration.

We considered 12 days as the interval between administration of a booster dose and its potential effect on the observed number of confirmed infections. Choosing the time period of at least 12 days after the booster vaccination where the cut-off was scientifically justified from an immunological perspective, as studies have shown that after a booster dose, neutralization levels do not increase until after several days.6 In addition, when confirmed infection (that is, positive in the PCR assay) is used as a result, a delay occurs between the date of infection and the date of the PCR test. For symptomatic cases, infection is likely to occur on average 5-6 days before testing, similar to the incubation period for Covid-19.12, 13 Thus, the period we chose from 12 days included 7 days until effective accumulation of antibodies after vaccination plus 5 days of delay in infection detection.

To estimate the reduction in rates of confirmed infection and severe disease among booster recipients, we analyzed data on confirmed infection rate and severe disease rate among fully vaccinated participants who received a booster dose (booster group) and those who received only two doses of vaccine (non-booster group). Membership in these groups was dynamic, since participants who were initially included in the non-booster group left after receiving the booster dose and were subsequently included in the booster group after 12 days, provided they had no confirmed infection during the interim period (Fig. S3).

In each group, we calculated the rate of both confirmed infection and severe illness per person per day at risk. In the booster group, we considered days at risk to begin 12 days after receiving the third dose and end either at the time of the study outcome or at the end of the study period. In the non-booster group, days at risk began 12 days after the start of the study period (August 10, 2021) and ended at the time of study outcome occurrence, at the end of the study period, or at the time of receipt of a booster dose. The time of severe Covid-19 onset was considered the date of confirmed infection. In order to reduce the problem of oversight, the severe disease rate was calculated based on cases confirmed on or before August 26, 2021. This schedule was adopted to allow one week of follow-up (up to the date when we extracted the data) to determine whether severe disease has progressed. The study protocol is available at


The study was approved by the Sheba Medical Center Institutional Review Board. All authors contributed writing and critical review of the manuscript, approved the final version, and made the decision to submit the manuscript for publication. The Israeli Ministry of Health and Pfizer have a data-sharing agreement, but only the final results of this study have been shared.

statistical analysis

We performed Poisson regression to estimate a given outcome rate, using the function to fit generalized linear models (glm) in the R statistical program.14 These analyzes were adjusted for the following covariates: age (60 to 69 years, 70 to 79 years, 80 years), gender, demographic group (general population of Jews, Arabs, or ultra-Orthodox Jews),8 The date of the second vaccine dose (every half a month). We included the date of the second dose as a covariate to account for the waning effect of previous vaccination and for possible early vaccination in high-risk groups.2 Because the overall rate of both confirmed infection and severe illness increased significantly during the study period, days at the beginning of the study period had the lowest exposure risk than days at the end. To account for the increased exposure risk, we included the calendar date as an additional variable. After calculating these variables, we used the study group (enhanced or non-reinforced) as a factor in the regression model and estimated its effect on the rate. We estimated the rate ratio by comparing the non-boosted group to the booster group, a measure similar to relative risks. To report uncertainty about our estimate, we took the exponent of the 95% confidence interval for the regression coefficient without adjustment for multiplicity. We also used the model results to calculate the average difference between groups in rates of confirmed infection and severe disease.15th

In a secondary analysis, we compared infection rates before and after a booster dose became effective. Specifically, we repeated the Poisson regression analysis described above but compared the confirmed incidence rate between 4 and 6 days after the booster dose to that of at least 12 days after the booster dose. Our hypothesis was that the booster dose was not yet effective during the previous period.10 This analysis compares the different periods after a booster vaccination among subjects who received a booster dose and may reduce selection bias. However, booster recipients may have undergone polymerase chain reaction (PCR) tests less frequently and act with greater caution regarding virus exposure soon after receiving the booster dose (Fig. Thus, we assume that the rate ratio can be underestimated in this analysis.

To further examine the decline in the confirmed incidence rate as a function of the time since reinforcer receipt, we fitted a Poisson regression incorporating days 1 to 32 after the booster dose as separate factors in the model. The period prior to receiving the booster dose was used as the reference category. This analysis was similar to the Poisson modeling described above and produced rates for different days after the booster vaccination.

To test for different potential biases, we performed several sensitivity analyses. First, we analyzed the data using alternative statistical methods based on matching and weighting. These analyzes are described in detail in the Methods section of the Supplementary Appendix. Second, we tested the effect of a specific study period by dividing the data into different study periods and performing the same analysis on each. Third, we performed the same analyzes using data from the general Jewish population only, in which participants in that group controlled the booster-vaccinated population.

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