Abstract
Background
Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic.
Methods
Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan–Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort.
Findings
Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15–180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18–39 years, but was not detected for those aged 40 years or older.
Interpretation
The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.
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Introduction
Although vaccine program is an effective strategy in fighting against the COVID-19 pandemic [1,2,3], the current global predominance of SARS-CoV-2 Omicron variants continuously challenges vaccine-induced protection, which was recognized by the World Health Organization (WHO) as one of the major public health concerns. Evidence from recent studies also suggested that the immunity generated by vaccination may wane over time [4,5,6,7,8,9,10], and Omicron variants were associated with increased transmissibility and immune escape ability [11,12,13,14,15]. The booster dose of vaccines was used to enhance immunity levels [16, 17], and was reported to provide relatively high protection against symptomatic to severe COVID-19 outcomes, including hospitalization, need for intensive care, and death [18,19,20,21,22,23,24]. Most existing estimates of vaccine effectiveness (VE) against Omicron infections have focused on various mRNA vaccines, including mRNA-1273 and BNT162b2, or adenovirus vector vaccines, such as ChAdOx1-nCoV-19 [24,25,26,27,28]. The COVID-19 vaccines received by almost all vaccinees in mainland China were Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac) inactivated COVID-19 vaccines, mainly BBIBP-CorV in Urumqi city (the city where the cohort was recruited in our study). Although the efficacy of inactivated vaccines was assessed in phase III clinical trials [17, 29], the real-world evidence of the effectiveness of inactivated vaccines remains largely unassessed [30, 31], especially considering the challenges caused by genetic variants of SARS-CoV-2, and immunity waning after vaccination.
Considering that the majority of Omicron infections may not progress to pneumonia and some of them are subclinical [32, 33], real-world evidence of VE in preventing mild and asymptomatic Omicron infections is generally lacking, but it is important for develo** herd immunity. The evaluation of VE against asymptomatic and mild infections is potentially challenging because infections without identifiable symptoms were less likely to be ascertained. As such, VE estimates under common study designs, including test-negative designs, could bias toward more severe clinical conditions or subgroups of populations with relatively high test-seeking behaviors [34], which may fail to be a fair representation of all infections. To our knowledge, there is only one study that assessed the effectiveness of inactivated vaccines against (asymptomatic and symptomatic) Omicron BA.2 infection in Hong Kong by using a cohort design, and the cohort was collected from participants randomly selected from the general population [35]. However, the contact tracing information was uninvestigated in their study, such that the determinants that contribute to secondary transmission, e.g., contact settings or the vaccination status of source cases, and then the downstream infection of close contacts remained unadjusted for or studied. In addition, the ongoing (as of December 2022) COVID-19 pandemic was dominated by Omicron BA.5 and its genetic sublineages [36], which have replaced Omicron BA.2 globally since the middle of 2022; thus, updating the VE against the (most recent) circulation SARS-CoV-2 variants may inform the risk assessment of current COVID-19 situations.
In this study, we assessed the effectiveness of the booster dose of inactivated vaccines against asymptomatic and symptomatic Omicron BA.5 infections in a well-traced cohort including all documented adult COVID-19 close contacts from August 1 to September 7, 2022. This cohort was collected from an infection-naive population with relatively high vaccination coverage in Urumqi, the capital and largest city in the ** severe clinical conditions of COVID-19, and the VE among the elderly is also far less than that for young people [61,62,63].
We reported that the VE was high when both infected individuals and their contacts were vaccinated with three doses. This finding was compatible with the first point of our findings that the overall effectiveness of booster vaccination against Omicron variant infection outperformed that of the primary series of two-dose vaccination. Unlike other places outside mainland China, quarantine and lockdown have been implemented for a longer time as a pandemic intervention strategy in the ** herd immunity. The assessment of vaccine effectiveness (VE) against asymptomatic Omicron infections generally lacking because the ascertainment of asymptomatic or mild infections was potentially challenging, despite the majority of Omicron infections being asymptomatic. Thus, VE estimates under common study designs, including test-negative designs, could bias toward more severe clinical conditions or subgroups of populations with high test-seeking behaviors. As of December 2022, we found 1 peer-reviewed cohort study based on the population in Hong Kong, China that assessed the VE of BNT162b2 and CoronaVac against asymptomatic Omicron BA.2 infection using real-world individual-level data. Owning to the previous “zero-COVID” policy in mainland China, COVID-19 was at a relatively low level before December 2022, and thus no VE estimate of BBIBP-CorV against Omicron infection in mainland China was published. To our knowledge, to date (December 2022), no study has reported the VE of BBIBP-CorV booster against Omicron BA.5 asymptomatic infection.
Added value of this study: in an Omicron BA.5 seeded outbreak in Urumqi, the capital and largest city in **njiang Uygur Autonomous Region of China, we identified 37,628 adult close contacts of COVID-19 with 2 or 3 doses of inactivated vaccines before exposure from August 1 to September 7, 2022. After matching for baseline conditions, we assessed the effectiveness of inactivated COVID-19 vaccines (mainly BBIBP-CorV) against Omicron infection, regardless of symptoms, in a real-world setting. The overall VE of booster dose versus 2-dose against Omicron BA.5 infection was 35.5% (95% CI 2.0, 57.5), with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15–180 days after vaccination, but decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. These findings were the first VE estimates against SARS-CoV-2 Omicron BA.5 infection in mainland China.
Implications of all the available evidence: moderate but significant protective effects against asymptomatic and symptomatic Omicron BA.5 infection were found for the booster doses of inactivated vaccine. The VE estimates were important contributions to informing vaccination policy in places where vaccine coverage remains low or inactivated vaccines were in-use. Thus, it is important to assess the vaccine performance against emerging genetic variants of SARS-CoV-2, as they evolved, regardless of the background vaccine coverage.
Data availability
The original database containing confidential patient information cannot be made publicly available. The anonymized data used in this study were available based on reasonable request to the corresponding authors.
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Acknowledgements
We thank all participants in this study for their cooperation in disease surveillance and control measure. We also thank healthcare professionals, caregiver partners, and public health practitioners for their contributions to the community.
Funding
This study was supported by Natural Science Foundation of **njiang (Grant No. 2021D01C268), Collaborative Research Fund (Grant No. C7123-20G) of the Research Grants Council (RGC) of Hong Kong, China, National Natural Science Foundation of China (Grant Nos. 12171192, 12071173, 11961071), and the Youth Science and Technology Innovation Talent of the Tianshan Talent Training Program in **njiang, China (Grant No. 2022TSYCCX0099).
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Conceptualization: SZ and KW. Methodology: SZ, TZ, YL and ZG. Software: KW, TZ and YL. Validation: ZG and SZ. Formal analysis: KW, MT and ZT. Investigation: KW, TZ, YL and SZ. Resources: YL, YC and KW. Data curation: JW, SL and XF. Writing—original draft: TZ, YZ, ZG and YL. Writing—review and editing: SS, ZT, MT, JW, SL, XF, WW, YC, GL, XL, DH and SZ. Visualization: YL, TZ and ZG. Supervision: KW and SZ. Project administration: KW, WW and YL. Funding acquisition: TZ, WW, YC, DH and KW. All authors critically read the manuscript and gave final approval for publication.
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The collection of specimens, epidemiological and clinical data for SARS-CoV-2 infected individuals and their close contacts is a part of a continuing public health investigation of COVID-19 outbreaks, ruled in the Protocol on the Prevention and Control of COVID-19 by the National Health Commission of the People’s Republic of China, which was exempt from ethical approval (i.e., institutional review board assessment). This study was approved by the institutional ethics committee of **njiang Medical University (IRB No. XJYKDXR20221001001). Individual verbal consent was obtained when collecting personal information and human samples by governmental healthcare professionals in the field.
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All authors declared no competing interests. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
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Zeng, T., Lu, Y., Zhao, Y. et al. Effectiveness of the booster dose of inactivated COVID-19 vaccine against Omicron BA.5 infection: a matched cohort study of adult close contacts. Respir Res 24, 246 (2023). https://doi.org/10.1186/s12931-023-02542-y
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DOI: https://doi.org/10.1186/s12931-023-02542-y