Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals

Abstract

Background The purpose of this study was to evaluate whether boosting previously infected or vaccinated healthcare personnel with a vaccine developed for an earlier variant of SARS-CoV-2 protects against the Omicron variant. Methods Employees of Cleveland Clinic previously infected with or vaccinated against COVID-19, and 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 SARS-CoV-2 exposure 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 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 (HR, .43; 95% CI, .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, 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 after prior infection or vaccination, protects against Omicron variant infection in those previously infected or vaccinated. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.

Protective effectiveness of prior SARS-CoV-2 infection and hybrid immunity against Omicron infection and severe disease: a systematic review and meta-regression

“…Sixteen unique articles reporting data for 26 studies were included for analysis. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Seven articles reported data for multiple studies, defined by multiple sets of study methods and independent populations with unique estimates of protection. Eleven studies reported on prior infection and 15 studies reported on hybrid immunity, which included six reporting on both.…”

Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine

“…A large study found, in an adjusted analysis, that those who had an Omicron variant infection after previously receiving three doses of vaccine had a higher risk of reinfection than those who had an Omicron variant infection after previously receiving two doses of vaccine [22]. Another study found, in multivariable analysis, that receipt of two or three doses of a mRNA vaccine following prior COVID-19 was associated with a higher risk of reinfection than receipt of a single dose [7]. We still have a lot to learn about protection from COVID-19 vaccination, and in addition to a vaccine's effectiveness, it is important to examine whether multiple vaccine doses given over time may not be having the beneficial effect that is generally assumed.…”

“…A large study found, in an adjusted analysis, that those who had an Omicron variant infection after previously receiving three doses of vaccine had a higher risk of reinfection than those who had an Omicron variant infection after previously receiving two doses of vaccine [22]. Another study found, in multivariable analysis, that receipt of two or three doses of a mRNA vaccine following prior COVID-19 was associated with a higher risk of reinfection than receipt of a single dose [7]. Immune imprinting from prior exposure to different antigens in a prior vaccine [22,23], and class switch towards non-inflammatory spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination [24], have been suggested as possible mechanisms by why prior vaccine may provide less protection than expected.…”

“…Covariates collected were age, gender, job location, and job type categorization into clinical or non-clinical, as described in our earlier studies [5][6][7]. Institutional data governance rules related to employee data limited our ability to supplement our dataset with additional clinical variables.…”

“…Previously infected or vaccinated individuals were no longer protected from COVID-19 [6]. Vaccine boosting provided some protection against the Omicron variant [7,8], but the degree of protection was not near that of the original vaccine against the pre-Omicron variants of SARS-CoV-2 [8]. After the emergence of the Omicron variant, prior infection with an earlier lineage of the Omicron variant protected against subsequent infection with a subsequent lineage [9], but such protection appeared to wear off within a few months [10].…”