Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

Abstract

ImportanceThe benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear.ObjectiveTo estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people.DesignTest-negative case-control study.SettingYale New Haven Health System facilities serving southern Connecticut communities.ParticipantsVaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022.ExposureCOVID-19 mRNA primary and booster vaccination.Main Outcomes and MeasuresWe conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and ≥150 days, respectively, after 2nd dose) and of booster vaccination (≥14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people.ResultsOverall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56).Conclusions and RelevancePrimary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection

“…Compared to prior studies, 8,26–28 our estimates for protection against reinfection were substantially lower than those analyzing infections during pre-Omicron outbreaks; furthermore, we found significant differences in protection conveyed by prior infections before and during the emergence of the Delta variant. Consistent with other studies 11,14 , we found the highest levels of protection among those who had three doses of vaccination and prior infections. Among those with prior infection, the incremental protection afforded by vaccination was substantial, especially vaccination with three doses, which raised protection against Omicron infection to levels similar to those reported in pre-Omicron studies of vaccination with the primary series.…”

“…Compared to prior studies, 8,26-28 our estimates for protection against reinfection were substantially lower than those analyzing infections during pre-Omicron outbreaks; furthermore, we found significant differences in protection conveyed by prior infections before and during the emergence of the Delta variant. Consistent with other studies 11,14 , we found the highest levels of protection among those who had three doses of vaccination and prior infections.…”

“…Among people with prior infection, evidence of the additional benefit of a third dose is limited. A cohort study within another healthcare system in the United States did not find significant additional protection among those with prior infections for people vaccinated with three doses compared to people eligible for a third-dose 14 . Our main analysis of the primary vaccine series mixes both third-dose ineligible and third-dose eligible people, thus providing a potentially inflated estimate of effectiveness for those vaccinated with two doses only.…”

“…Recent studies have shown continued effectiveness of vaccination against hospitalizations or death [10][11][12][13] , though reduced effectiveness for confirmed 11,14 and symptomatic illness 10,15,16 with Omicron. While some studies have reported estimates of hybrid immunity against infection with Omicron 10,14 , information among individuals with recent and remote prior infections remains limited.…”

Protection against Omicron BA.2 reinfection conferred by primary Omicron or pre-Omicron infection with and without mRNA vaccination

“…19 Studies examining protection against Omicron reinfection (BA.1 or any sublineage) have reported that prior pre-Omicron on infection was associated with moderate effectiveness (25% to 47%), but stronger against severe outcome (>80%), and improved with vaccination. 12,[18][19][20][21][22] As reported in our study, a third dose among previously infected individuals was associated to a transient increase in protection both against Omicron BA.1 and BA.2 subvariants. 12,19,20 Evidence about cross-protection between different Omicron sublineages is scarce.…”