Effectiveness of Original Monovalent and Bivalent COVID-19 Vaccines Against COVID-19-Associated Hospitalization and Severe In-Hospital Outcomes Among Adults in the United States, September 2022–August 2023

Background: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes. Methods: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case–control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region. Results: Among 7028 patients, 2924 (41.6%) were COVID-19 case patients, and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute VE against COVID-19-associated hospitalization was 6% (−7%–17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304–571]), 52% (39%–61%) for a bivalent dose received 7–89 days earlier, and 13% (−10%–31%) for a bivalent dose received 90–179 days earlier. Absolute VE against COVID-19-associated invasive mechanical ventilation or death was 51% (34%–63%) for original monovalent doses only, 61% (35%–77%) for a bivalent dose received 7–89 days earlier, and 50% (11%–71%) for a bivalent dose received 90–179 days earlier. Conclusion: Bivalent vaccination provided protection against COVID-19-associated hospitalization and severe in-hospital outcomes within 3 months of receipt, followed by a decline in protection to a level similar to that remaining from previous original monovalent vaccination by 3–6 months. These results underscore the benefit of remaining up to date with recommended COVID-19 vaccines.