• Ronen Arbel, Wolff SagyYaelYFrom the Division of Community Medical Services (R.A., A.P., S.Y., D.S., A.H., D.N.), the Branch of Planning and Strategy (Y.W.S., M.H., E.B., G.L.), and the Clalit Research Institute, Division of Innovation (J.G.W., N.D., R.B., Y.B.-S.), C, Moshe Hoshen, Erez Battat, Gil Lavie, Ruslan Sergienko, Michael Friger, Jacob G Waxman, Noa Dagan, Ran Balicer, Yatir Ben-Shlomo, Alon Peretz, Shlomit Yaron, Danielle Serby, Ariel Hammerman, and Doron Netzer.
• From the Division of Community Medical Services (R.A., A.P., S.Y., D.S., A.H., D.N.), the Branch of Planning and Strategy (Y.W.S., M.H., E.B., G.L.), and the Clalit Research Institute, Division of Innovation (J.G.W., N.D., R.B., Y.B.-S.), Clalit Health Services, Tel Aviv, the Maximizing Health Outcomes Research Lab, Sapir College, Sderot (R.A.), the Department of Bioinformatics, Jerusalem College of Technology, Jerusalem (M.H.), the Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa (G.L.), and the School of Public Health, Faculty of Health Sciences (R.S., M.F., R.B.) and Software and Information Systems Engineering (N.D.), Ben-Gurion University of the Negev, Beersheba - all in Israel; and the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration, Harvard Medical School and Clalit Research Institute (N.D., R.B.), and the Department of Biomedical Informatics, Harvard Medical School (N.D.) - both in Boston.
• N. Engl. J. Med. 2022 Sep 1; 387 (9): 790798790-798.

BackgroundThe oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited.MethodsWe obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status.ResultsA total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75).ConclusionsAmong patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.Copyright © 2022 Massachusetts Medical Society.

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