After Three Sinopharm Doses, an mRNA Booster Was Linked to Lower Odds of Omicron Infection in a Macao Survey
Assessing the effects of a booster after inactivated vaccines
People who received one messenger RNA (mRNA) vaccine dose after three doses of the Sinopharm inactivated vaccine had lower odds of reporting a confirmed Omicron infection than people who received three inactivated-vaccine doses alone. This was the finding of an online survey of 4,879 Macao residents. Because this was not a trial that randomly assigned vaccination groups or tracked infections, the results should be interpreted as an association between vaccination regimen and outcome.
In regions that relied mainly on inactivated vaccines, there was interest in whether adding a vaccine from another platform could help protect people under real-world outbreak conditions. Macao supplied Sinopharm and BioNTech mRNA vaccines and experienced an Omicron BF.7 and BA.5.2 wave in late 2022. The research team compared infection status, fever, and the duration of test positivity across vaccination regimens.
Lower odds of infection and fever with a specific regimen
The survey was distributed through WeChat on December 27–28, 2022. Of 5,803 responses collected by convenience sampling, 4,879 were included after applying the exclusion criteria; the age range shown in the table was 12–60 years. Vaccination history and infection status were self-reported. Confirmed infection was defined as a positive rapid antigen test or nucleic acid test, and 71.4% of all respondents reported a confirmed infection.
The main comparison was between 1,391 people who received three Sinopharm inactivated-vaccine doses and 118 who received one ancestral-strain mRNA vaccine dose in addition. After adjustment for sex, age, work and residential conditions, and time since the last vaccination, the odds ratio (OR) for confirmed infection in the mRNA-booster group was 0.421 (P<0.01). This means adjusted odds were 57.9% lower than in the reference group. It does not mean that infection probability or relative risk fell by the same proportion.
Results also differed by vaccination regimen. The infection OR was 0.790 in the group that received one ancestral-strain mRNA dose after two inactivated-vaccine doses; the reported statistical evidence was at the P<0.1 level. This is why the value of 0.421 cannot be applied to all heterologous booster groups.
The OR for fever in the group that received one mRNA dose after three inactivated-vaccine doses was 0.290 (P<0.01). Fever was defined as a temperature of at least 37.5°C. The abstract describes this result as being among infected people, but the fever model in Table 3 includes all 4,879 respondents. It is difficult to conclude that this estimate comes from a comparison limited to infected people.
In a model analyzing the period from the first positive test to the first negative test, the same vaccination group was associated with a period of test positivity 0.931 days shorter than that of the reference group (P<0.05). Viral load and replication rate were not measured directly.
The implications and limits of short-term observational evidence
These findings add real-world outbreak data relevant to considering an mRNA booster after inactivated vaccines. However, antibody and T-cell responses were not measured, so there is no basis for conclusively attributing the observed differences to a specific immune mechanism.
Bias related to the characteristics of online respondents and nonrandom vaccine choices, as well as residual confounding, may remain. Older adults and children were excluded, and people with severe illness may have been less able to participate. The fever result should not be extrapolated to protection against hospitalization, severe disease, or death. There is also some ambiguity between the sample size for the test-positivity-duration analysis and a table footnote describing the exclusion of respondents who were still positive at the time of the survey. The duration difference therefore cannot readily be treated as a fully observed recovery outcome for all infected people.
The research team suggested the possibility of short-term protection from a recent booster, while leaving long-term effects and safety for future study. This survey cannot establish whether the same effects occur with current circulating variants or in other age groups. The study design and results by vaccination group are available in the full Journal of Thoracic Disease article.
Oncology & Infectious Disease Core, Published online: 22 May 2026. DOI: [Source Generated Data]
Summary: Evaluating the immunogenicity gaps within populations predominantly immunized with inactivated virus platforms, this real‑world retrospective cohort registry captures the interventional efficacy of heterologous mRNA booster sub‑regimens during the 2022 Omicron wave (BF.7 and BA.5.2 subvariants) in Macao. Utilizing a high‑throughput cohort profile of 4,879 validated residents, logistic and ordinary least squares (OLS) regression matrices were deployed to isolate confounding sociodemographic factors. Compared against the homologous three‑dose inactivated baseline, the heterologous mRNA architecture demonstrated a robust reduction in confirmed infection velocity [Odds Ratio (OR) = 0.421]. Concurrently, among infected sub‑cohorts, the heterologous prime‑boost interface driven by mRNA integration programmatically attenuated pyretic progression [OR = 0.290] and truncated the viral clearance kinetics baseline by -0.931 sick days, solidifying a scalable computational standard for international heterologous immunization policies.
For regions with vaccination histories centered on inactivated vaccines, this study offers a concrete example of why booster strategies should distinguish both vaccine combinations and the timing of the last dose. Public health authorities can consider the findings for the group that received one mRNA dose after three Sinopharm doses alongside other observational studies and clinical trials. However, the adjusted odds ratio alone is insufficient to calculate an individual's probability of avoiding infection or to justify a wholesale policy shift. The survey addressed short-term infection, fever, and the duration of test positivity in young and middle-aged people. Assessing protection against severe disease in older adults, long-term safety, and vaccination strategies matched to current variants requires further evidence directly evaluating the relevant populations and outcomes.