Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes

Abstract

Background: To inform planning for further booster doses of COVID-19 vaccines, we estimated the effectiveness of monovalent mRNA vaccines against Omicron-associated severe outcomes in adults over time. Methods: We used a test-negative design and multivariable logistic regression to estimate vaccine effectiveness (VE; 2, 3, or 4 doses compared to unvaccinated individuals) and marginal effectiveness (3 or 4 doses compared to 2 doses) against Omicron-associated hospitalization or death among community-dwelling adults aged ≥50 years who were tested for SARS-CoV-2 between January 2, 2022 and October 1, 2022 in Ontario, Canada, stratified by age group and time since vaccination. We also compared VE during periods of Omicron BA.1/BA.2 and BA.4/BA.5 sublineage predominance. Results: We included 11,160 cases of Omicron-associated severe outcomes and 62,880 test-negative symptomatic controls. Depending on the age group, compared to unvaccinated individuals, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. Trends in marginal effectiveness were consistent with VE estimates. VE was lower during the BA.4/BA.5-predominant period compared to the BA.1/BA.2-predominant period based on the same intervals since vaccination. Conclusion: Our findings suggest that 1 or 2 booster doses of monovalent mRNA COVID-19 vaccines initially restored very strong protection against Omicron-associated severe outcomes in all age groups, but VE subsequently declined over time with some age-related differences, and particularly so during a period of BA.4/BA.5 predominance.

Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

“…Covid-19 vaccination policies recommending the bivalent mRNA-booster vaccines as a fourth dose are mainly supported by studies on immunogenicity where some have shown higher induction of antibody levels against omicron subvariants including BA.4-5 compared with monovalent boosters. [4][5][6][7][8] Previous observational effectiveness studies of fourth dose monovalent vaccination, primarily on data from before BA.4-5 subvariant predominance, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] also lend some indirect support to these recommendations.…”

“…[9][10][11][12] Previous observational studies of fourth doses are primarily limited to the monovalent mRNA Covid-19 vaccines and mainly during periods prior to the emergence of the current predominating omicron subvariants BA.4 and BA.5. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] As such, data on the effectiveness of the bivalent mRNA-vaccines are needed to guide Covid-19 vaccination policy and to evaluate the benefit of developing variant-adapted Covid-19 vaccines.…”

Effectiveness of SARS-CoV-2 Vaccines against Omicron Infection and Severe Events: A Systematic Review and Meta-Analysis of Test-Negative Design Studies

“…However, a caveat is that nearly all data used to estimate the long-term VE of the second booster against severe disease came from the same study among elderly residents of long-term care facilities in Ontario, Canada. 61 In addition, this long-term VE is against BA.1 and BA.2, the dominant subvariants during the study period of 31 Dec 2021 to 27 April 2022, according to the Ontario Ministry of Health.…”

“…After removing duplicates, 1,236 articles remained, of which 116 were considered relevant after inspection of the title, abstract, and keywords. These 116 relevant articles were then reviewed in full text for eligibility, and 11 articles 23,37,[54][55][56][57][58][59][60][61][62] with 46 VE estimates were finally included in this meta-analysis (supplementary materials p 19). More summary details and detected publication bias of the included studies are given in the supplementary materials (p 2).…”

The impact of comorbidity status in COVID-19 vaccines effectiveness before and after SARS-CoV-2 omicron variant in northeastern Mexico: a retrospective multi-hospital study

“…In the present study data is divided in two periods of the COVID-19 pandemic which correspond to the period before and after Omicron as it has been shown that in pre-Omicron vaccines, the efficacy against Omicron infection is comparatively lower than that observed for Delta and Alpha strains. Furthermore, the effectiveness of these vaccines in preventing Omicron infection tends to diminish at a faster rate over time (63,64). According to the WHO, 63% of the total Mexican population has a complete primary series of COVID-19 (65).…”