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Coronavirus Disease 2019 (COVID-19) Vaccine Boosting in Persons Already Protected by Natural or Vaccine-Induced Immunity

Background. The purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant. Methods. Employees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate. Results. Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). Conclusions. Administering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.