Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA–Vaccinated and Nonvaccinated Individuals in Quebec, Canada

Abstract

ImportanceThe Omicron variant is phylogenetically and antigenically distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron reinfection, with and without vaccination, requires quantification.ObjectiveTo estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine.Design, Setting, and ParticipantsThis test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada.ExposuresPrior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination.Main Outcomes and MeasuresThe main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 − the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose.ResultsThis study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning.Conclusions and RelevanceThe findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

Prior infection- and/or vaccine-induced protection against Omicron BA.1, BA.2 and BA.4/BA.5-related hospitalisations in older adults: a test-negative case-control study in Quebec, Canada

“…Extrapolation to newly circulating sublineages requires caution. Despite these limitations, our data align with and confirm observations from other immunological and epidemiological studies, [4][5][6][7][8][9][10][11] while our analysis of three sublineages simultaneously, notably including BA.4/5, updates understanding and enables within lineage comparison as well as cross-reference with previous studies of vaccine and hybrid immunity against BA.1 and BA.2 only.…”

“…2 BA.4 and BA.5 (BA.4/5) demonstrate substantial escape from vaccine or infection-induced neutralizing antibodies but this immune evasion is less pronounced in individuals with hybrid immunity resulting from both prior infection and vaccination. 3 Vaccine effectiveness (VE) against SARS-CoV-2 is reduced and of shorter duration for omicron compared to the delta variant, [4][5][6] and for the BA.4/5 omicron sublineage compared to BA.1 or BA.2. [7][8][9] Stronger and longer-lasting VE during BA.1 and BA.2 dominant periods was reported among individuals with history of prior infection, 10,11 but similar data for hybrid immunity against BA.4/5 are lacking, including for severe outcomes or by number of vaccine doses, type of prior infection (pre-omicron or omicron) or duration since the last immunological event.…”

Serial cross-sectional estimation of vaccine-and infection-induced SARS-CoV-2 seroprevalence in British Columbia, Canada

“…Multiple immunological, epidemiological and modelling studies suggest that having had both vaccination and infection exposures contributes to stronger, broader and more durable hybrid immunity than with either exposure alone, especially against severe outcomes. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] The extent to which such exposure history should guide recommendations regarding booster doses depends on several factors, recognizing that a large proportion may not even be aware of their previous infection status. 48 Moreover, the antigenic relatedness and immunological interactions between previously infecting viruses, the original monovalent vaccines, more recently updated bivalent vaccine strains, and currently circulating or emerging variants are complex and dynamic.…”

Primary and booster vaccination in reducing severe clinical outcomes associated with Omicron Naïve infection

“…While a body of evidence has shown the effectiveness of reducing in severity and death related to various SARS-CoV-2 variants including the wild type/D614G [20] , [21] , Alpha VOC (20-22), Beta [22] , [23] , Gamma [24] , Delta [25] , [26] , [27] , and Omicron [27] , [28] , [29] , [30] , the recent studies have focused on whether and how prior infections may affect the effectiveness of mass vaccination [7] , [31] , [32] , [33] , [34] . Considering prior infection is particularly important when population-based effectiveness of vaccination against the recent Omicron VOC infection needs to be evaluated as most of countries worldwide have seen incessant large-scale community-acquired outbreaks before Omicron VOC infection [1] , [7] , [8] .…”