• Ori Magen, Jacob G Waxman, Maya Makov-Assif, Roni Vered, Dror Dicker, Miguel A Hernán, Marc Lipsitch, Ben Y Reis, Ran D Balicer, and Noa Dagan.
• From the Clalit Research Institute, Innovation Division (O.M., J.G.W., M.M.-A., R.D.B., N.D.), and the Tel-Aviv District, Community Division (R.V.), Clalit Health Services, and the Sackler Faculty of Medicine, Tel-Aviv University (D.D.), Tel Aviv, the Department of Internal Medicine D, Hasharon Hospital Rabin Medical Center, Petah Tikva (D.D.), and the School of Public Health, Faculty of Health Sciences (R.D.B.), and the Department of Software and Information Systems Engineering (N.D.), Ben Gurion University of the Negev, Be'er Sheva - all in Israel; and the Departments of Epidemiology and Biostatistics and CAUSALab (M.A.H.) and the Center for Communicable Disease Dynamics, Departments of Epidemiology and of Immunology and Infectious Diseases (M.L.), Harvard T.H. Chan School of Public Health, the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute (B.Y.R., R.D.B., N.D.), the Predictive Medicine Group, Computational Health Informatics Program, Boston Children's Hospital (B.Y.R.), and the Departments of Pediatrics (B.Y.R.) and Biomedical Informatics (B.Y.R., N.D.), Harvard Medical School - all in Boston.
• N. Engl. J. Med. 2022 Apr 28; 386 (17): 160316141603-1614.

BackgroundWith large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose.MethodsTo evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19-related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression.ResultsThe primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction-confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19-related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19-related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19-related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis.ConclusionsA fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19-related outcomes among persons who had received a third dose at least 4 months earlier. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).Copyright © 2022 Massachusetts Medical Society.

37 keywords...

hide…