Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals.

Background: The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant.

Methods: Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure.

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 proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, receipt of 2 compared with 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 after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.