Effectiveness of Bivalent Booster Vaccine in Preventing Severe COVID-19 Outcomes in High-Risk Adults
There has been a low uptake of bivalent mRNA booster vaccines in older adults, despite a high efficacy of preventing severe and fatal COVID-19.
In the latter part of 2022, the Omicron BA.5 sublineage became the predominant COVID-19 strain worldwide, as evidenced by the sequencing of viral genomes. Since its emergence, Omicron continues to cause numerous severe and fatal COVID-19 infections.
Previous studies have shown that booster immunization with monovalent mRNA vaccines against earlier variants is highly effective in preventing COVID-19. However, the efficacy of monovalent mRNA boosters against Omicron is lower compared to other COVID-19 variants, and its protective effect diminishes significantly after 3-4 months post-vaccination.
Therefore, there is a strong interest in developing new vaccines that contain different variants to induce broader immune responses and provide enhanced protection against severe outcomes.
In August 2022, the US Food and Drug Administration (FDA) approved bivalent formulations of the Moderna and Pfizer COVID-19 mRNA vaccines as a single booster dose for individuals who had completed their primary vaccination series or received a monovalent booster.
These bivalent vaccines consist of an ancestral COVID-19 strain component and an updated component containing the omicron BA.4 and BA.5 sublineages. The approval was based on safety and immune response data for the bivalent booster, along with previous data on the safety and effectiveness of the monovalent booster.
Bivalent mRNA vaccines have replaced monovalent boosters in several countries, including the USA and Israel. In Israel, the prioritization of bivalent mRNA boosters is primarily for individuals aged 65 years or older who are at high risk of severe COVID-19.
One study, published in The Lancet Infectious Diseases, aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose in preventing hospitalizations and deaths due to COVID-19.
The retrospective, population-based cohort study was based in Israel. Investigators utilized electronic medical records from Clalit Health Services (CHS), a large healthcare organization. The study period spanned from September 27, 2022, to January 25, 2023, with a data extraction date of January 29, 2023.
The study cohort included all CHS members aged 65 years or older who were eligible for a bivalent mRNA COVID-19 booster vaccination. Eligibility criteria required participants to have had at least 3 months since their last vaccination, at least 3 months since their last COVID-19 infection, and completion of the primary two-dose monovalent mRNA vaccination series.
The primary endpoint of the study was COVID-19-related hospitalization, while the secondary endpoint was death due to COVID-19. Demographic data, previous immunity factors, and clinical risk factors for severe COVID-19 were collected for each participant. Statistical analysis, including univariate and multivariable survival analyses, was conducted to estimate the association between bivalent mRNA booster vaccination and COVID-19-related hospitalizations and deaths.
To address censoring, a multivariable Cox proportional hazards regression model with time-dependent covariates was utilized. The model adjusted for sociodemographic factors, previous immunity factors, and coexisting illnesses. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to determine the number needed to vaccinate to prevent 1 hospitalization or death due to COVID-19.
The findings of our study indicate that among adults aged 65 years or older, the bivalent BA.4 and BA.5 mRNA vaccine booster dose has a vaccine effectiveness of 72% (95% CI 60-81) for preventing hospitalization due to COVID-19 and 68% (95% CI 42-82) for preventing death due to COVID-19. The participants who received a bivalent booster vaccine had lower hospitalization rates for up to 120 days after vaccination.
The bivalent mRNA booster vaccine campaign in Israel primarily targeted high-risk older adults. Despite an ample supply of vaccines with no reported shortages, this retrospective study revealed a relatively low uptake of the bivalent booster vaccine in this group, at only 24%. Comparatively, the United States had an even lower uptake of 10% as of November 15, 2022, according to the US Centers for Disease Control and Prevention (CDC).
In this Israeli study, the number needed to vaccinate to prevent one COVID-19-related death was 3722 people (95% CI 3086-6026), which was more than three times higher than that for the first monovalent booster vaccine (n = 1166, 95% CI 816-1633). The higher number needed to vaccinate for the bivalent vaccine primarily resulted from its lower effectiveness and higher hazard ratio (HR) in reducing COVID-19 deaths compared to the first monovalent booster (0.32 vs. 0.10).
These findings underscore the clinical significance of administering a bivalent mRNA vaccination booster dose to this high-risk population and emphasize the need to intensify efforts to encourage eligible individuals to get vaccinated. The study authors recommended this be achieved through government initiatives aimed at countering misinformation, enhancing confidence in vaccine safety and efficacy, building trust in the healthcare system, and engaging healthcare providers to endorse vaccination.
