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

Abstract

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.

Effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 infection in Guangdong, China: a cohort study

“…Our results confirmed that booster vaccination could only provide a low level of protection against Omicron infection and symptomatic COVID-19 in adults 18-59 years, but a high level of protection against COVID-19 pneumonia in adults ≥ 60 years old when compared with full vaccination. To the best of our knowledge, there were only two published studies that reported the relative effectiveness of booster vaccination with inactivated COVID-19 vaccines against infection caused by the Omicron variant ( 5 , 17 ). In a test-negative case-control study in Guangzhou, China, the booster dose of inactivated COVID-19 vaccines did not provide any protection against Omicron infection when compared with full vaccination ( 17 ).…”

“…To the best of our knowledge, there were only two published studies that reported the relative effectiveness of booster vaccination with inactivated COVID-19 vaccines against infection caused by the Omicron variant ( 5 , 17 ). In a test-negative case-control study in Guangzhou, China, the booster dose of inactivated COVID-19 vaccines did not provide any protection against Omicron infection when compared with full vaccination ( 17 ). A study in Hong Kong showed that the effectiveness of booster vaccination against mild or moderate COVID-19 caused by the Omicron BA.2 variant was 35·7% and 46.9% among the subjects aged 20-59 and ≥ 60 years old, respectively ( 5 ).…”

“…However, the real-world evidence about the role of booster vaccination of inactivated COVID-19 vaccines against infection of the Omicron BA.2 variant remains limited. Although several studies have assessed the effectiveness of the booster dose of inactivated COVID-19 vaccines made in China ( 5 , 6 , 14 – 17 ), these studies only analyzed the absolute VE of the booster dose but did not compare with full vaccination ( 6 , 14 – 17 ) except for two studies that reported the relative VE of booster vaccination by comparing with full vaccination ( 5 , 17 ). One study in Hong Kong assessed the effectiveness of the CoronaVac vaccine against Omicron BA.2 sub-lineage infection and showed extra protection against severe COVID-19 over full vaccination ( 5 ).…”

“…One study in Hong Kong assessed the effectiveness of the CoronaVac vaccine against Omicron BA.2 sub-lineage infection and showed extra protection against severe COVID-19 over full vaccination ( 5 ). Another study in Guangzhou, China indicated that booster vaccination with inactivated vaccines did not provide any protection against Omicron BA.2 infection when compared with full vaccination ( 17 ). As SARS-CoV-2 Omicron variants keep emerging and show resistance to the neutralizing anti-SAR-CoV-2 antibodies, accelerated expansion and administration of booster vaccination of COVID-19 vaccines are ongoing ( 18 – 23 ).…”

A Review of Inactivated COVID-19 Vaccine Development in China: Focusing on Safety and Efficacy in Special Populations

“…However, another study showed an increased risk of Omicron infection among people aged 18 to 59 who had been vaccinated once, twice, or three times. The authors caution that these results may be due to the limited sample size in the study and the viral nature of Omicron BA.2 [ 43 ].…”