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 infection notified during the BA.5 dominated period with any prior SARS-CoV-2 infection. 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 first infections, 233,424 (1.2%) were reinfected with BA.5. The protective effect against BA.5 reinfection of prior infection with Wuhan strain was 46%, Alpha variant was 35%, Delta variant was 41%, and BA.1/BA.2 subvariant was 74%. The reduced risk of BA.5 reinfection by 7%, 33%, and 66% was associated with 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: None.