Post-doctoral research fellow Kaiser Permanente Southern California, United States
Background: Individuals aged ≥50 years are at a higher risk of severe COVID-19 disease. While the uptake of the monovalent primary series is high in the older U.S. population, booster vaccine uptake is low. Real-world data are limited for the effectiveness of 4 doses of mRNA-1273 vaccine among the general U.S. population aged ≥50 years and by subgroups.
Objectives: To evaluate the relative vaccine effectiveness (rVE) of 4 doses of monovalent mRNA-1273 compared to 3 doses against SARS-CoV-2 infection and COVID-19 hospitalization and death in immunocompetent individuals aged ≥50 years during the omicron period.
Methods: We conducted a matched cohort study among immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California (KPSC). Eligible 4-dose monovalent mRNA-1273 recipients were 1:1 matched to randomly selected 3-dose monovalent mRNA-1273 recipients by age, sex, race/ethnicity, and third dose date. Fourth doses were accrued between 03/29/2022 and 07/31/2022, with follow-up through 08/31/2022. Index date was the date of 4th dose for 4-dose recipients, and the same index date assigned to their matched 3-dose counterparts. Individuals were followed for outcomes (SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death) from 14 days after the index date until end of follow-up (08/31/2022), termination of KPSC membership, death, or receipt of an additional COVID-19 vaccine, whichever occurred first. Hazard ratios (HR) were estimated using Cox proportional hazards regression comparing the incidence of outcomes between the 4-dose and 3-dose groups. rVE (%) was calculated as (1 – HR) × 100.
Results: We included 178,492 immunocompetent adults aged ≥50 years who received 4 doses of mRNA-1273. The cohort was 55% female and 44% non-Hispanic White, with a mean age of 69 years (standard deviation 10). Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death was 25.9% (95% CI: 23.5-28.2%), 67.3% (58.7-74.1%), and 72.5% (-35.9-95.2%), respectively. Adjusted rVE against SARS-CoV-2 infection was higher (27.2% [24.8-29.6%]) for symptomatic infection compared to asymptomatic infection (8.8% [-2.1-18.5%]), and ranged between 19.8 and 39.1% across subgroups of age, sex, race/ethnicity, and comorbidity. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased after 2 months after the 4th dose.
Conclusions: Four doses of mRNA-1273 provided additional protection against SARS-CoV-2 infection and severe COVID-19 outcomes compared to 3 doses in individuals aged ≥50 years across various subgroups of demographic/clinical characteristics, although rVE varied and waned over time.
