Assessing the Reactogenicity of Homologous and Heterologous COVID-19 Vaccine Schedules

Introduction: COVID-19 vaccines were considered as the most effective mode to prevent morbidity and mortality from COVID-19. However, similar to other vaccines, adverse events post-vaccination is expected. This reactogenicity to vaccines varies by type of vaccine and vaccine dose and has primarily been studied in clinical trials with homologous dosing of vaccines. However, due to variation in vaccine availability and perceived and actual risk of serious adverse events within a few months of vaccine rollout, heterologous schedules were implemented in different countries worldwide, including Australia. This thesis aims to: 1) describe the vaccine reactogenicity profiles of the different homologous and heterologous schedules from published studies, and 2) determine the reactogenicity of Therapeutic Goods Administration approved homologous and heterologous schedules using the AusVaxSafety data. Methods: The first study is a systematic review and meta-analysis guided by the PRISMA framework, which included randomised controlled trials, open trials and cohort studies involving participants 18 years old above who have received at least 2 doses of any WHO validated for emergency use COVID-19 vaccines. The second study is a prospective cohort study using the AusVaxSafety active surveillance system to determine risks of adverse events following the second or third dose of COVID-19 vaccination in the different homologous and heterologous schedules. Results and Conclusion: Findings from the systematic review indicated higher local and systemic reactogenicity of homologous mRNA schedules, and heterologous schedules with mRNA vaccines as second or third dose. Similarly, the AusVaxSafety cohort study suggested higher risk of adverse events in homologous mRNA vaccine schedules as well as heterologous schedules utilising mRNA vaccines as a second dose. Further studies exploring the heterogeneity in reporting frequencies of AEFIs, and cohort studies including all the AusVaxSafety-linked survey tools are recommended to determine optimal COVID-19 schedules for future vaccine guidelines.