• Yinon M Bar-On, Yair Goldberg, Micha Mandel, Omri Bodenheimer, Ofra Amir, Laurence Freedman, Sharon Alroy-Preis, Nachman Ash, Amit Huppert, and Ron Milo.
• From the Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot (Y.M.B.-O., R.M.), Technion-Israel Institute of Technology, Haifa (Y.G., O.A.), the Hebrew University of Jerusalem, (M.M.) and the Israel Ministry of Health (O.B., S.A.-P., N.A.), Jerusalem, the Bio-statistical and Bio-mathematical Unit, the Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan (L.F., A.H.), and the Faculty of Medicine, Tel Aviv University, Tel Aviv (A.H.) - all in Israel.
• N. Engl. J. Med. 2022 May 5; 386 (18): 1712-1720.

BackgroundOn 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).MethodsUsing 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.ResultsThe 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.ConclusionsRates 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.Copyright © 2022 Massachusetts Medical Society.

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