In a recently published study in the MMWR and Morbidity and Mortality Weekly Report, researchers retrospectively analyzed two cohorts of Medicare participants to estimate the effectiveness of bivalent mRNA COVID-19 vaccines in preventing COVID-19-related thromboembolic events compared to original monovalent vaccines. They found that the efficacy of bivalent COVID-19 vaccine doses against thromboembolic events in Medicare participants aged ≥65 years was 47%, and 51% in adults aged ≥18 years with end-stage renal disease (ESRD) receiving dialysis.
Complications associated with COVID-19 include an increased risk of thromboembolic events, especially among individuals aged ≥65 years and those with end-stage renal disease receiving dialysis. Although COVID-19 vaccination has shown a protective effect against severe outcomes and lower rates of COVID-19-related thromboembolic events in vaccinated individuals, comprehensive estimates of VE specifically against these events are lacking. This study aimed to close this gap by assessing the comparative effectiveness of bivalent COVID-19 mRNA vaccines in preventing COVID-19-related thromboembolic events compared to original monovalent vaccines alone. The study focused on older Medicare beneficiaries and adults with end-stage renal disease undergoing dialysis, aiming to provide insights into VE, stratified by time since dose, compared to COVID-19-related thromboembolic complications in these populations.
The study included two retrospective cohort analyses targeted at Medicare beneficiaries aged ≥65 years (n = 5,683,208) and individuals aged ≥18 years with end-stage renal disease receiving dialysis (n = 23,229). Comprehensive data on eligibility, covariates, COVID-19 vaccine status, and outcomes were collected using Medicare Parts A and B claims data. Eligible recipients received the bivalent COVID-19 mRNA vaccine, and cohort formation began on September 4, 2022. Daily updates of vaccine status commenced seven days after the bivalent vaccine dose, with follow-up until the conclusion of the study on March 4, 2023. Censoring events included COVID-19-related thromboembolic events. Using a marginal structural Cox model, the analysis estimated the relative effectiveness of the vaccine, providing insights into the incremental benefits of bivalent doses compared to original monovalent vaccine doses. Statistical significance was determined by two-sided 95% confidence intervals, with non-overlapping intervals indicating significant differences in effectiveness estimates.
Results and Discussion
A higher proportion of recipients receiving bivalent doses lived in urban areas and had received a flu vaccine and a dose of the original monovalent COVID-19 booster vaccine in the years 2021–22 and 2022–23.
During the study, COVID-19-related thromboembolic events were observed in 22,001 participants aged ≥65 years and 1,040 participants aged ≥18 years receiving dialysis for end-stage renal disease. Among Medicare beneficiaries aged ≥65 years who received only a monovalent vaccine dose, 17,746 COVID-19-related thromboembolic events were observed. In contrast, 4,255 events were reported among those who received a bivalent vaccine dose. Thus, the adjusted VE in this cohort was 47%. Notably, VE estimates were higher (54%) during 7–59 days after receiving the bivalent vaccine, compared to estimates after ≥60 days (42%).
On the other hand, 917 COVID-19-related thromboembolic events were observed in the cohort of individuals aged ≥18 years with end-stage renal disease receiving dialysis who received only the monovalent vaccine dose. However, only 123 events were observed among those who received a bivalent vaccine dose. Thus, the adjusted VE in this group was 51%. As seen in the cohort ≥65 years, VE estimates were higher (56%) during 7–59 days after receiving the bivalent vaccine than VE estimates after ≥60 days (45%). However, no statistically significant difference was observed. Participants with additional immunocompromised conditions also showed similar results.
The results indicate the additional benefit of a current bivalent dose compared to previous administration of original monovalent doses and align with the reported lower incidence of COVID-19-related thromboembolic events in vaccinated individuals compared to unvaccinated individuals. The study emphasizes the protective effect of bivalent COVID-19 vaccination against COVID-19-related thromboembolic events in these high-risk populations and provides insights for risk-benefit assessments. The researchers note that the protective effect of bivalent vaccine doses wanes over time, but further investigations are needed as the study only examined two time periods since the last dose.
The study is limited by inadequate ascertainment of COVID-19 vaccine receipt, lack of consideration for prior SARS-CoV-2 infections, the influence of policy implementation timelines, potential residual confounding, and reliance on medical claims data. Additionally, the scope of the study is limited to Medicare beneficiaries, restricting its generalizability to the entire US population.
In conclusion, the study demonstrates that receiving all recommended COVID-19 vaccine doses is crucial for individuals aged 65 years and older and adults with end-stage renal disease undergoing dialysis to reduce the risk of thromboembolic events and other COVID-19-related complications.