Protective effect of previous infection and vaccination against reinfection with BA.5 Omicron subvariant: a nationwide population-based study in Japan

Background: The Omicron variant of SARS-CoV-2 was reported to evade immunity derived from vaccination and previous infection. A better understanding of hybrid immunity informs effective infection control strategies. Since the reinfection risk was not well-assessed in East Asia, this study aims to evaluate the risk of infection with Omicron subvariant BA.5 among previously infected individuals in Japan.Methods: All notified cases were extracted from the Japanese national COVID-19 surveillance database including 20,297,335 records up to 25 September 2022. Reinfection with BA.5 was defined as the second infection notified during the BA.5 dominated period. The protective effect of prior infections against reinfections with BA.5 was estimated by applying a case-population design and the protective effect of vaccination was estimated by a multivariable Cox regression adjusting for age, sex, variants of prior infection, and the time since the last vaccination.Findings: Among 19,830,548 SARS-CoV-2 infections, 233,424 (1·2%) were reinfected with BA.5. The protective effect of prior infection with Wuhan, Alpha, Delta, and BA.1/BA.2 against BA.5 reinfection was 46·2% (45·5–47·0), 35·2% (34·2–36·2), 40·6% (39·9–41·2), and 73·9% (73·4–74·4), respectively. The risk of BA.5 reinfection was reduced by 14%, 41%, and 71% by two, three and four doses of vaccination, respectively, compared with one-dose vaccination.Interpretation: The prior infections with Omicron subvariant BA.1/BA.2 protected BA.5 reinfection more than pre-Omicron variants. Increased frequency of vaccination led to more protection from reinfection with BA.5. Up-to-date vaccination may be encouraged to prevent future reinfection among the previously infected population.Funding: RK received funding from the Japan Society for the Promotion of Science (JSPS) KAKENHI (21K17307). MS and TK received the Ministry of Health Labour and Welfare Science Research Grant (23HA2005).Declaration of Interest: The authors declare that they have no conflict of interest.Ethical Approval: No ethical approval was required because this study was conducted for public health purposes using national surveillance data.