New report examines the safety of bivalent COVID boosters in 1.7 million people over the age of 50

In a recent study posted on medrex sib*, Danish researchers examined the risk of adverse events following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-based bivalent booster vaccination.

Bivalent messenger ribonucleic acid (mRNA) boosters targeting the ancestral SARS-CoV-2 and Omicron BA.1 or BA.4/5 spikes were approved for use in 2022. Regardless of boosting with monovalent vaccine (third dose or first booster).

Denmark will begin rolling out bivalent boosters on 15 September 2022 for people over the age of 50 and those at risk of severe COVID-19. The regulatory safety evaluation of bivalent boosters is based on pre-approval clinical studies, clinical data on reactogenicity and immunogenicity, and post-marketing safety data on monovalent vaccines.

A recent study reported that the safety profile of bivalent BA.4/5-based boosters appeared similar to that of monovalent boosters. However, boosters have not been statistically tested and data on the risk of adverse events following bivalent booster administration are needed.

study: Safety of Bivalent Omicron-Containing mRNA Booster Vaccines: A National Cohort StudyImage Credit: Jo Panuwat D / Shutterstock

About research

In this study, researchers investigated the association between SARS-CoV-2 Omicron-based bivalent booster vaccination and potential risk of adverse events in Denmark. We linked data from national medical records on vaccination, diagnosis, and covariates to create a general population-based cohort.

Danish residents over the age of 50 were eligible if they received 3 doses of the monovalent COVID-19 vaccine. Individuals were excluded if their third or her fourth vaccination was within 90 days of his last vaccination. The primary risk period was 28 days after bivalent vaccination and the reference period began 29 days after her third or fourth dose.

The team assessed the potential risk of 27 adverse events of the SARS-CoV-2 vaccine. The outcome event was a hospital visit, and the outcome diagnosis was the primary reason for seeking hospital care. Subjects were followed from Day 29 after the 3rd/4th dose until first outcome, emigration, death, or study termination.

A Poisson regression model was developed to calculate the incidence rate ratio and compare the risk period outcome rate with the reference period outcome rate. The model was adjusted for age group, gender, ethnicity, region of residence, his risk of severe COVID-19, comorbidities, and calendar time.

The researchers examined associations by age, sex, and type of bivalent booster, and assessed the risk of serious adverse events in secondary analyses. The robustness of findings was determined using self-administered case series (SCCS) analysis and calculating the ratio of observed to expected rates of findings.

findings

Overall, more than 2.2 million triple-vaccinated individuals were included in the cohort. The average age she was 66.9 years old and most (52%) were female. Of these, more than 1.7 million (78.2%) subjects were boosted with the bivalent vaccine between 15 September 2022 and 10 December 2022.

The BA.4/5-based bivalent vaccine was the most administered, followed by the BA.1-based vaccine. The team found that a fourth vaccination with a bivalent Omicron-based booster was not associated with more hospital visits for adverse events within 28 days after vaccination. No significant associations were observed after stratification by stratum, sex, or type of bivalent vaccine.

SCCS and observed versus expected rate ratio analyzes revealed comparable results to the primary analysis. In one of the secondary analyses, the risk of serious outcome events was similar to that observed in the primary analyses. Furthermore, applying different risk periods showed an increased risk of myocarditis/pericarditis within 14 days. Finally, the investigators performed a post hoc analysis to assess the risk of pericarditis, cerebrovascular infarction, and myocarditis.

This revealed no association between bivalent vaccination and cerebrovascular infarction risk. Nine cases of myocarditis and 22 cases of pericarditis were observed within 28 days after bivalent vaccination. There was a significant association between women and Pfizer BA.4/5-based and Moderna BA.1-based bivalent boosters with myocarditis. No association with pericarditis was observed.

Conclusion

In summary, the investigators estimated the incidence of adverse events after bivalent booster vaccination in Danish residents aged 50 years and over who received three doses of the vaccine. The risk of adverse events did not increase after he received a bivalent booster as the fourth dose. A post hoc analysis revealed higher hospital visits for women with myocarditis. Together, these results ensure the safety of bivalent booster vaccination and provide timely and important insights for regulators, clinicians, and patients.

*Important Notices

medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.