Sex Differences in Serious Adverse Events Reported Following Booster Doses of COVID-19 Vaccination in Thailand: A Countrywide Nested Unmatched Case-Control Study

Abstract

A booster dose of a COVID-19 vaccine has been proven effective in restoring vaccine effectiveness and is currently recommended for use in some populations at risk of severe COVID-19 infection. Since sex differences in adverse events are significant in response to the vaccines, the safety of booster selection must be studied to avoid serious adverse events (SAE), such as life-threatening diseases. First, this study aimed to identify sex differences in SAE incidences using a prospective cohort design. Second, a nested unmatched case-control study was used to identify factors associated with reported SAE within 30 days after the booster shot. Multivariable logistic regression indicated the adjusted odds ratio by accounting for host and vaccine variables, thus, policy effects. The findings confirmed that SAE was rare and that age-sex-dominated disease classifications differed. Specific to SAE following the booster dose, we found that females aged 12–40 had a higher risk of being reported with SAE than males of the same age, while males over 50 had a higher risk than females. Other risk factors identified were the presence of metabolic syndrome and the use of certain vaccine brands. Mechanisms could be explained by individual host responses rather than the vaccines’ direct effect. Therefore, SAE could be preventable by age-sex-specific vaccine selection, post-vaccination precautions, and early symptom detection. Future vaccine development should aim to limit host-specific reactogenicity for safety concerns.

Keywords

• serious adverse events
• COVID-19 vaccines
• booster doses
• sex difference
• BNT162b2
• mRNA-1273