COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination - 24 U.S. Jurisdictions, October 3, 2021-December 24, 2022

Abstract

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.^† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks-2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6-8 (RR = 4.6), 9-11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks-2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.

FIGURE 1

Age-standardized weekly COVID-19 incidence and COVID-19–associated mortality rates,† by vaccination status and receipt of a bivalent booster dose — 24 U.S. jurisdictions, October 2021–December 2022** * Cases per 100,000 persons aged ≥12 years. COVID-19 cases among unvaccinated persons and persons vaccinated with a primary series with or without a monovalent or bivalent booster dose were defined as previously described (https://www.cdc.gov/coronavirus/2019-ncov/php/hd-breakthrough.html). Cases with primary series or a monovalent booster were combined in the “vaccinated only with monovalent vaccines” category. Cases were excluded among persons who received ≥1 Food and Drug Administration–authorized vaccine dose but did not complete a primary series ≥14 days before the positive specimen collection date. ^† Deaths per 100,000 persons aged ≥12 years. A COVID-19–associated death occurred in a person with a documented COVID-19 diagnosis who died, and whose report local health authorities reviewed to make that determination (e.g., using vital records, public health investigation, or other data sources). Per national guidance, this group should include persons whose death certificate lists COVID-19 or SARS-CoV-2 as an underlying cause or a significant condition contributing to death. Rates of COVID-19 deaths by vaccination status are reported based on when the patient was tested for COVID-19, not the date the patient died. ^§ Bivalent boosters were recommended during September 1–December 24, 2022. Based on case definitions, a case after vaccination occurred in a person ≥14 days postvaccination. ^¶ These 24 jurisdictions represent 52% of the overall U.S. population and were included in this analysis: Alabama, Arizona, Arkansas, Colorado, District of Columbia, Georgia, Idaho, Indiana, Kansas, Kentucky, Louisiana, Massachusetts, Michigan, Minnesota, Nebraska, New Jersey, New Mexico, New York, North Carolina, Tennessee, Texas, Utah, Washington, and West Virginia; New York did not provide mortality data. ** Date range for age-standardized weekly COVID-19 incidence is October 3, 2021–December 24, 2022; date range for COVID-19–associated mortality rates is October 3, 2021–December 3, 2022.

FIGURE 2

Age-standardized average weekly case and mortality rate ratios with 95%CIs in unvaccinated persons compared with booster dose recipients, by variant period and time since receipt of last booster dose — 23 U.S. jurisdictions, October 2021–December 2022^§§ * Cases per 100,000 persons aged ≥12 years. COVID-19 cases among unvaccinated persons and persons vaccinated with a primary series with or without a monovalent or bivalent booster dose were defined as previously described (https://www.cdc.gov/coronavirus/2019-ncov/php/hd-breakthrough.html). Cases were excluded in persons who only completed a primary series or who received ≥1 Food and Drug Administration–authorized vaccine dose but did not complete a primary series ≥14 days prior to the positive specimen collection date. ^† A COVID-19–associated death occurred in a person with a documented COVID-19 diagnosis who died, and whose report local health authorities reviewed to make that determination (e.g., using vital records, public health investigation, or other data sources). Per national guidance, this group should include persons whose death certificate lists COVID-19 or SARS-CoV-2 as an underlying cause or a significant condition contributing to death. Rates of COVID-19 deaths by vaccination status are reported based on when the patient was tested for COVID-19, not the date the patient died. ^§ 95% CIs were calculated after detrending underlying linear changes in weekly rates using piecewise linear regression. Each 95% CI represents the remaining variation in observed weekly rates and resulting rate ratios. The number of observations leading to each 95% CI reflects the number of weeks per period: Delta (11), Omicron BA.1 (13), Omicron BA.2 (14), early Omicron BA.4/BA.5 (12), and late Omicron BA.4/BA.5 (14). ^¶ Analysis periods were categorized based on variant predominance (defined as accounting for >50% of sequenced lineages): Delta, October 3–December 18, 2021; Omicron BA.1, December 19, 2021–March 19, 2022; Omicron BA.2, March 20–June 25, 2022; early Omicron BA.4/BA.5, June 26–September 17, 2022; and late Omicron BA.4/BA.5 (only period where bivalent boosters were recommended), September 18–December 24, 2022. ** Time since last monovalent booster categories was restricted to outcomes occurring during eligible weeks based on the timing of the first booster recommendation for adults aged ≥65 years and adults aged ≥18 years in high-risk groups on September 24, 2021: 2 weeks–2 months (starting October 3, 2021); 3–5 months (starting November 13, 2021); 6–8 months (starting February 13, 2022); 9–11 months (starting May 15, 2022); ≥12 months (starting August 14, 2022). For persons aged 12–17 years, boosters were recommended on January 5, 2022; data are included the week starting January 16, 2022. Bivalent boosters were included for the period starting September 18, 2022, and for categories of 2 weeks–2 months and 3 months after receipt of a booster for cases and 2 weeks–2 months after receipt of a booster for deaths. Unvaccinated persons are compared to vaccinated persons for the same time frame in each category. The median interval in the 2 weeks–2 months since vaccination period was longer for persons with monovalent boosters during early (60 days) and late (70 days) BA.4/BA.5 periods than for those who received bivalent boosters (47 days). The median interval among persons who received a monovalent booster 3–5 months earlier was 131 and 191 days, respectively, during early and late BA.4/BA.5 periods; among those who received bivalent boosters 3 months earlier, the median interval was 95 days. ^†† These 23 jurisdictions represent 50% of the overall U.S. population and were included in this analysis: Alabama, Arizona, Arkansas, Colorado, District of Columbia, Georgia, Idaho, Indiana, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Nebraska, New Jersey, New Mexico, New York, North Carolina, Tennessee, Texas, Utah, Washington, and West Virginia; New York did not provide mortality data. ^§§ Date range for age-standardized average weekly case rate ratio is October 3, 2021–December 24, 2022; date range for mortality rate ratio is October 3, 2021–December 3, 2022.