Protective Effect of Inactivated COVID-19 Vaccines Against Omicron BA.2 Infection in Guangzhou: A Test-Negative Case-Control Real-World Study

This study aims to explore the relationship between the doses of inactivated COVID-19 vaccines received and SARS-CoV-2 Omicron infection in the real-world setting, so as to preliminarily evaluate the protective effect induced by COVID-19 vaccination. We conducted a test-negative case-control study and recruited the test-positive cases and test-negative controls in the outbreak caused by Omicron BA.2 in April 2022 in Guangzhou, China. All the participants were 3 years and older. The vaccination status between the case group and the control group was compared in the vaccinated and all participants, respectively, to estimate the immune protection of inactivated COVID-19 vaccines. After adjusting for sex and age, compared with a mere single dose, full vaccination of inactivated COVID-19 vaccines (OR = 0.191, 95% CI: 0.050 to 0.727) and booster vaccination (OR = 0.091, 95% CI: 0.011 to 0.727) had a more superior protective effect. Compared with one dose, the second dose was more effective in males (OR = 0.090), as well as two doses (OR = 0.089) and three doses (OR = 0.090) among individuals aged 18–59. Whereas, when compared with the unvaccinated, one dose (OR = 7.715, 95% CI: 1.904 to 31.254) and three doses (OR = 2.055, 95% CI: 1.162 to 3.635) could contribute to the increased risk of Omicron infection after adjusting for sex and age. Meanwhile, by contrast with unvaccinated individuals, the result of increased risk was also manifested in the first dose in males (OR = 12.400) and one dose (OR = 21.500), two doses (OR = 1.890), and a booster dose (OR = 1.945) in people aged 18–59. In conclusion, the protective effect of full and booster vaccination with inactivated COVID-19 vaccines exceeded the incomplete vaccination, of which three doses were more effective. Nevertheless, vaccination may increase the risk of Omicron infection compared with unvaccinated people. This may result from the transmission traits of BA.2, the particularity and stronger protection awareness of the unvaccinated population, as well as the ADE effect induced by the decrease of antibody titers after a long time of vaccination. It is crucial to explore this issue in depth for the formulation of future COVID-19 vaccination strategies.