Protection of SARS-CoV-2 natural infection against reinfection with the Omicron BA.4 or BA.5 subvariants

<jats:title>Abstract</jats:title><jats:p>This study estimates the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test-negative, case–control study design. Cases (SARS-CoV-2-positive test results) and controls (SARS-CoV-2-negative test results) were matched according to sex, 10-year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S-gene “target failure” (SGTF) infections between May 7, 2022-July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022-July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a pre-Omicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5’s greater capacity for immune-system evasion than that of BA.1/BA.2.</jats:p>