Protection by a Fourth Dose of BNT162b2 against Omicron in Israel

Abstract

Background: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).

Methods: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.

Results: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.

Conclusions: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.

Figure 1. Study Population.

The study included persons who were 60 years of age or older who had not been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before the study period, were eligible for the fourth dose of the BNT162b2 vaccine by the end of the study period, had available data regarding sex and demographic group, had not stayed abroad for the entire study period, and had not received a coronavirus disease 2019 (Covid-19) vaccine other than BNT162b2 before the study period.

Figure 2. Adjusted Rate Ratios for Confirmed Infection and Severe Illness.

Shown are adjusted rate ratios for confirmed SARS-CoV-2 infection and severe Covid-19 in the group of persons eligible for a fourth dose who had not yet received it (three-dose group) as compared with those who had received a fourth dose, as a function of time since the fourth dose (the higher the rate ratio, the greater the protection conferred by the fourth dose of vaccine). Persons in the internal control group had received a fourth dose 3 to 7 days earlier (a period in which the fourth dose was not expected to affect the rate of confirmed infection or severe illness). Because of the 14-day follow-up period for severe Covid-19, the study period for this outcome was 2 weeks shorter than that for confirmed infection, and therefore the estimates of the adjusted rate ratio for severe illness end at week 6 instead of week 8.