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

Abstract

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.

Vaccine-induced and naturally-acquired protection against Omicron and Delta symptomatic infection and severe COVID-19 outcomes, France, December 2021 to January 2022

“…In our study, the first booster is associated with a lower risk of COVID-19 both among those with a primary vaccination course as well as those with natural immunity. This is consistent with other results obtained during an Omicron variant surge [ 9 ]. Against the Omicron variant, our findings are in favour of a greater or equal protection of natural immunity in the first six months following prior infection compared to a vaccine primary course, but of a lower protection compared to a vaccine primary course followed by a recent booster dose.…”

“…Thus, this study does not inform on the natural or hybrid immunity attributable to Omicron infection. In our study period, prior infections are likely homogeneous with respect to symptomatology and thus ascertainment, which will not necessarily be the case in the future due to the potentially milder symptomatology of the Omicron variant [ 6 , 9 , 12 , 13 ]. To maximise external validity, we used a rather liberal definition of the Delta and Omicron variants based on screening methods.…”

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

“…Serologic data indicate that antibody responses to Omicron can be at least partially boosted in the short term (up to $1 month) after a 3rd vaccine dose (Muecksch et al, 2022;Muik et al, 2022;Schmidt et al, 2021b;Xia et al, 2022), suggesting that immunological memory generated by 2-dose vaccination has some reactivity against the Omicron spike protein. A 3rd vaccine dose also provides increased protection from Omicron variant infection (Shrestha et al, 2022). However, it is unclear how long these boosted antibody responses to Omicron may last and what percent of memory B cells retain binding to Omicron and other variants.…”

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

“…Serologic data indicate that antibody responses to Omicron can be at least partially boosted in the short-term (up to ∼1 month) after a 3 rd vaccine dose ( 22–25 ), suggesting that immunological memory generated by 2-dose vaccination has some reactivity against the Omicron Spike protein. A 3 rd vaccine dose also provides increased protection from Omicron variant infection ( 26 ). However, it is unclear how long these boosted antibody responses to Omicron may last and what percent of memory B cells retain binding to Omicron and other variants.…”