3-Does Inactivated Vaccine with 1-Does Mrna Providing Strong Protection Against COVID-19 Infection Among Young and Middle-Age Groups during 2022 Omicron Wave in Macao (China): An Observatory Study

Objectives: Using self-reported vaccination record and COVID-19 infection status, this study is aimed to analyze the protection effectiveness provided by heterologous mRNA vaccine boosters during the 2022 Omicron Wave in Macao (China).Methods: Utilizing observational data collected through a representative online survey among Macao residents, this study examined whether mixed vaccination is associated with better protection from COVID-19 infection and milder symptoms if infected.Results: Compared with those having 3-dose inactivated vaccine, respondents with mixed vaccination (GGB, GGGB, GGMB, GGM, GGGM and GGMM) had significantly lower likelihood of reporting confirmed infection, or fever if infected, and shorter days testing positive. The protection effects of 3-does inactivated vaccine with 1-does mRNA (GGGM) are especially strong, being equivalent with 2 doses of mRNA with 1-dose bivalent booster (MMB0), and only weaker than 3 doses of mRNA with 1-dose bivalent booster (MMMB).Conclusion: The results of this study provide population-level empirical evidence for the effectiveness of heterologous mRNA vaccine boosters in protecting against COVID-19 infections. It provides strong evidence to support the strategy of encouraging mRNA boosters to follow inactivated vaccine primary series, emphasizing the policy importance of promoting mixed vaccination strategies among nations that use inactivated vaccine as the primary series.Funding: This work was supported by Science and Technology Development Fund of Macau SAR (005/2022/ALC); Self-supporting Program of Guangzhou Laboratory (SRPG22-007); Science and Technology Development Fund of Macau SAR (0045/2021/A); and Macau University of Science and Technology (FRG-20-021-MISE).Declaration of Interest: No competing financial, professional, or personal interests might have influenced the performance or presentation of the work described in this manuscript. The funder had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.Ethical Approval: This research program was approved by the ethics committee of Macao University of Science and Technology (Approval No.: MUST-FDCT-20230116001, dated 27 December 2022), which was conducted for Macao citizens, legal non-citizen residents with work permits or international student status, and incarcerated individuals. Participants were informed at the outset that their participation was voluntary and anonymous, and that their privacy would be strictly protected.