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

Abstract

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. 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. 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. 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. None.