Protection conferred by Delta and BA.1/BA.2 infection against BA.4/BA.5 infection and hospitalization: A Retrospective Cohort Study

Background SARS-CoV-2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. Methods This retrospective cohort study included individuals tested for COVID-19 by PCR during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection/hospitalization rate for initially positive patients divided by infection/hospitalization rate for initially negative patients, stratified by age, and adjusted for age, gender, comorbidities, and vaccination using logistic regression. Results 20,987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (Adjusted PF: 11.9% (95% confidence interval [CI], 0.8-21.8); p=0.036) and minimal protection against hospitalization (Adjusted PF: 10.7% (95%CI, 4.9-21.7); p=0.003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95%CI, 36.2-54.1) (p <0.001) protection against BA.4/BA.5 reinfection and 18.8% (95% CI, 10.3-28.3) (p<0.0001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. Conclusions Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization, and no infection protection.