Does the homologous booster with the inactivated coronavirus disease 2019 vaccine work for the omicron variant? Real-world evidence from Jilin, China : Chinese Medical Journal

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Does the homologous booster with the inactivated coronavirus disease 2019 vaccine work for the omicron variant? Real-world evidence from Jilin, China

Guo, Jun1; Zha, Lei2,3; Zeng, Kai4; Shao, Mingyu5; Chen, Dan6; Wang, Bing7; Zhou, Yun8; Yang, Gang8; Zhang, Xue1; Zou, Xia9; Zhang, Yan1; Kang, Yan1

Editor(s): Ni, Jing

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Chinese Medical Journal ():10.1097/CM9.0000000000002575, April 28, 2023. | DOI: 10.1097/CM9.0000000000002575

To the Editor: The latest variant of concern, Omicron, has become the dominant global variant immediately after it was first reported in November 2021.[1] It contains >30 mutations in the spike protein, with 17 mutations in the receptor-binding domain, rendering it with increased transmissibility and capacity for immune evasion.[1,2] Moreover, the waning of protection has been observed over time since the coronavirus disease 2019 (COVID-19) vaccination.[3] Therefore, a booster is highly recommended. A large-scale study in the UK assessing the effectiveness of the booster vaccination with either the BNT162b2 or mRNA-1273 indicated that the booster shot substantially increased protection against symptomatic infection in patients with the confirmed Omicron variant infection.[3] However, although the laboratory study has illustrated that the homologous booster with the inactivated COVID-19 vaccine could also yield potent neutralizing activity against the Omicron variant,[4] clinical evidence regarding the effectiveness of this vaccination program is limited.

To estimate the protective effect (PE) of the homologous booster vaccination program against severe to critical diseases, we conducted a retrospective cohort study by including adult symptomatic patients infected with the Omicron subvariant (BA.2) during the outbreak of COVID-19 in the Jilin province (13 March–20 April, 2022). Vaccination status was extracted from the provincial immunization management system. Patients were categorized into unvaccinated, partially vaccinated (PV), fully vaccinated (FV), and the booster group based on their vaccination status. The primary outcome was the PE of the inactivated COVID-19 vaccine against severe to critical COVID-19 which was estimated by calculating the risk ratio in each group in reference to the unvaccinated group with univariate and multivariate logistic regression and subtracted from one. The ethics committee in the Jilin Central General Hospital approved the study (No. 2022–135).

There were 3604 symptomatic patients with the Omicron subvariant (BA.2) infection included in the final analysis. One thousand and ninty-five (30.4%) of patients completed the primary vaccine course, 1052 (29.2%) received the booster vaccination, 926 (25.7%) of patients only received the first dose, and 530 (14.7%) did not receive any vaccine. Patients in the booster vaccination group all received homologous boosters. During their hospitalization, 116 (3.2%) patients developed severe to critical infection, with 54 (10.2%) in the unvaccinated group, 29 (3.1%) in the PV group, 29 (2.6%) in the FV group, and 4 (0.4%) in the booster group, respectively [Supplementary Table 1,].

In terms of the PE of the inactivated vaccine, the unadjusted effectiveness against severe to critical disease was 69.4% (95% confidence interval [CI], 52.6–80.3%) in PV patients, 74.1% (95% CI, 59.8–83.3%) in FV patients and 96.3% (95% CI, 89.8–98.6%) in patients with a booster vaccination. After adjusting for age and comorbidity, the PE was slightly lower than that of unadjusted but with a similar trend. The booster vaccination presented the highest protection against severe to critical disease (93.8%, 95% CI, 82.7–97.8%) [Figure 1].

Figure 1:
PE of the inactivated COVID-19 vaccine against severe to critical disease caused by the omicron variant. The unadjusted PE of the inactivated COVID-19 vaccine against severe to critical illness caused by the omicron variant was 69.4% (95% CI, 52.6–80.3%) in PV patients, 74.1% (95% CI, 59.8–83.3%) in FV patients and 96.3% (95% CI, 89.8–98.6%) in patients with a booster vaccination. After adjusting for age and comorbidity, the adjusted PE was 54.6% (95% CI, 28.9–71.1%) in PV patients, 64.8% (95% CI, 45.0–77.5%) in FV patients and was 93.8% (95% CI, 82.7–97.8%) in patients with a homologous booster shot. CI: Confidence interval; FV: Fully vaccinated; PE: Protective effect; PV: Partially vaccinated.

In the present study, we demonstrated that the homologous booster with the inactivated COVID-19 vaccine is effective in controlling the severity of the Omicron infection, as the adjusted PE against severe to critical illness reached 93.8% (95% CI, 82.7–97.8%). The results were similar to that reported in a large-scale study in Hong Kong, China, in which patients receiving boosters demonstrated a very high level of protection against severe outcomes (PE, 98.1%, 95% CI, 97.1–98.8%).[5] However, there are still concerns and challenges in implementing this COVID-19 vaccination policy.

The level of neutralizing antibodies against the Omicron variant in persons who received the inactivated COVID-19 vaccine was lower than those receiving the messenger RNA or adenoviral vector vaccine, even after the booster dose.[6] Moreover, a clinical study has already demonstrated the inferiority of the homologous booster with the inactivated COVID-19 vaccine in preventing infection and death during the prevalence of the Delta variant.[7] Therefore, it is rational to consider the possibility of implementing the heterogeneous program in China.

There were several limitations in the present study. First, the current study design failed us directly to estimate the vaccine effectiveness of the homologous booster program. Although an excellent PE has been demonstrated in the present study, well-designed test-negative case–control studies are still warranted to analyze the actual vaccine effectiveness of the current homologous booster program in preventing Omicron infections. Second, we did not incorporate the duration between the last dose of the vaccine and the infection into the final analysis, which is an essential factor affecting the effectiveness of the COVID-19 vaccine. Third, the history of previous COVID-19 was unclear, which might underestimate the actual effectiveness of the booster vaccination because patients with previous infections were less likely to complete the COVID-19 vaccination. Finally, all the patients included in the present study were from a single center, so selection bias might have existed. Despite these limitations, results from the present study still offered evidence supporting the reasonability and necessity of implementing the current booster vaccination policy in China.


We thank Miao Wang (Sichuan University), Anxin He (Conch Hospital of Anhui Medical University), and Guanghui Chen (Conch Hospital of Anhui Medical University) for the constructive discussion of data analysis and vaccine policies.


The study was partially supported by grants from the Key Research and Development Project of the Science and Technology Department of Sichuan Province (No. 2021YFS0003, Zygd18020) and the High-level Talents Fund of the Wuhu Municipal Government (No. 2021–134).

Conflicts of interest



1. Karim SSA, Karim QA. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet 2021;398:2126–2128. doi: 10.1016/s0140-6736(21)02758-6.
2. Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2022;602:671–675. doi: 10.1038/s41586-021-04389-z.
3. Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, et al. Covid-19 vaccine effectiveness against the omicron (B.1 1. 529) variant. N Engl J Med 2022;386:1532–1546. doi: 10.1056/NEJMoa2119451.
4. Yu X, Qi X, Cao Y, Li P, Lu L, Wang P, et al. Three doses of an inactivation-based COVID-19 vaccine induces cross-neutralizing immunity against the SARS CoV-2 Omicron variant. Emerg Microbes Infect 2022;11:749–752. doi: 10.1080/22221751.2022.2044271.
5. McMenamin ME, Nealon J, Lin Y, Wong JY, Cheung JK, Lau EHY, et al. Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study. Lancet Infect Dis 2022;22:1435–1443. doi: 10.1016/S1473-3099(22)00345-0.
6. Costa Clemens SA, Weckx L, Clemens R, Almeida Mendes AV, Ramos Souza A, Silveira MBV, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet 2022;399:521–529. doi: 10.1016/s0140-6736(22)00094-0.
7. Jara A, Undurraga EA, Zubizarreta JR, Gonzalez C, Pizarro A, Acevedo J, et al. Effectiveness of homologous and heterologous booster shots for an inactivated SARS-CoV-2 vaccine: a large-scale observational study. Lancet Glob Health 2022;10:798–806. doi: 10.1016/S2214-109X(22)00112-7.

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