Effectiveness of the Booster Dose of Inactivated COVID-19 Vaccine Against Omicron BA.5 Infection: a Matched Cohort Study of Adult Close Contacts

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.