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.