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.