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 univariable and multivariable 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 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.
Acknowledgments
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.
Funding
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
None.
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