evidence: During April 4–December 25, 2021, a total of 6,812,040 COVID-19 cases among unvaccinated persons and 2,866,517 cases among fully vaccinated persons were reported among persons aged ≥18 years in 25 U.S. jurisdictions; 94,640 and 22,567 COVID-19–associated deaths among unvaccinated and fully vaccinated persons, respectively, were reported by December 4 (Table 1). Average weekly, age-standardized rates of cases and deaths (events per 100,000 population) were higher during periods of Delta predominance and Omicron emergence than during pre-Delta and Delta emergence periods and were consistently higher in all periods among unvaccinated persons (range = 64.0–725.6 [cases] and 1.5–11.4 [deaths]) than among fully vaccinated persons (range = 7.4–230.9 and 0.1–0.7).