Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes
Open accessPreprint — published as 10.1038/s41467-023-36566-1
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.
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Eight studies assessed VE of primary series or first booster dose vaccination separately for at least two different Omicron subvariants (six assessed VE of both primary series and booster dose vaccination and two assessed VE of a booster dose only).
“Eight studies assessed VE of primary series or first booster dose vaccination separately for at least two different Omicron subvariants (six assessed VE of both primary series and booster dose vaccination and two assessed VE of a booster dose only, Tables 1 and 2) [21,24-26,28-33].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
The Introduction and Results (pages unavailable) show that this study assessed effectiveness after two doses and a third dose across BA.1/BA.2- and BA.4/BA.5-predominant periods. The Discussion explicitly says it could not estimate effectiveness against BA.1, BA.2, BA.4, and BA.5 separately. It therefore supports inclusion as a study comparing Omicron periods, but not the claim that it assessed individual subvariants separately. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVE estimates between BA.1/2 and BA.4/5 predominant periods were not significantly different in the first 120 days after the booster dose.
“Of note, the VE estimates between the BA.1/2 and BA.4/5 predominant periods were not significantly different in the first 120 days after the booster dose.”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
The Results (page not available) report a nonsignificant between-period difference 7–59 days after a third dose among adults aged 70–79 (p=0.08). That example supports the claim for one age group and interval, but the passages do not establish that differences were nonsignificant throughout the first 120 days after booster doses. The Discussion reports lower VE during BA.4/BA.5 predominance across the same post-vaccination intervals. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAmong three studies that compared VE against BA.1/2 with BA.4/5, one showed a similar VE within the first four months following a booster dose, but lower VE against BA.4/5 beyond 4 months; one study showed similar VE at all periods; the third showed lower VE against BA.4/5 than BA.1/2 at all periods, though confidence intervals overlapped.
“Among three studies that compared VE against BA.1/2 with BA.4/5, one showed a similar VE within the first four months following a booster dose, but lower VE against BA.4/5 beyond 4 months; one study showed similar VE at all periods; the third showed lower VE against BA.4/5 than BA.1/2 at all periods, though confidence intervals overlapped [21,28,30].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
The Results report lower VE during BA.4/BA.5-predominant periods than during BA.1/BA.2-predominant periods at the same post-vaccination intervals. The confidence intervals overlap in the reported 7–59-day example, but not in the 180–239-day example, so the unqualified statement about overlapping intervals is not supported throughout. This paper is one of the three studies cited; the other studies' findings are not being attributed to it. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSimilar trends were observed among the other age groups (though results presented for 70-79).
“Results were presented for 70-79-yearolds, although similar trends were observed among the other age groups.”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
For the single study that evaluated VE separately for four different age groups, all age groups were included in the meta-regression; a sensitivity analysis was conducted including only a single age group (70-79 years).
“For the single study that evaluated VE separately for four different age groups, all age groups were included in the meta-regression; a sensitivity analysis was conducted including only a single age group (70-79 years) [28].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
In the study from Ontario where differences in vaccine effectiveness between BA.1/2 and BA.4/5 periods were large, differences in time since last dose were less than one month between subvariant periods.
“In contrast, in the study from Ontario where differences in VE between the BA.1/2 and BA.4/5 periods were large, differences in time since last dose were less than one month between subvariant periods [28].”
From Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization (2023) · cites this paper as [28]
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Cites
A Bivalent Omicron-Containing Booster Vaccine against Covid-19
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Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shotPreprint
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Flagged first, then by citations
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Cited by
Sorted by citations
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- Authors
- Grewal, R., Nguyen, L., Buchan, S. A., Wilson, S. E., Nasreen, S., Austin, P. C., Brown, K. A., Fell, D. B., Gubbay, J., Schwartz, K. L., Tadrous, M., Wilson, K., & Kwong, J. C.
- Affiliations
- Public Health Ontario (CA)
- University of Toronto (CA)
- University of Ottawa (CA)
- University Health Network (CA)
- Corresponding author
- Kwong, Jeffrey C
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2022-11-01
- Volume
- 14
- Issue
- 1
- Pages
- 1273-1273
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9990563
- OpenAlex
- W4323534146
- Cited by
- 59
- References
- 12
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 15 · 2023: 22
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by)
- Funders
- Public Health Agency of Canada (CNF 151944, 151944)
- Public Health Agency
- University of Toronto
- Canadian Immunization Research Network (CNF 151944)
- Canadian Institutes of Health Research (151944, COVID-19, 151944_1)
- Department of Family and Community Medicine, University of Toronto
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- mRNA vaccines, Omicron subvariants, BA.4/BA.5, vaccine effectiveness, waning immunity, severe outcomes, hospitalization, mortality, older adults, test-negative design, Ontario
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adult, Humans, Immunization, Secondary, Ontario, RNA, Messenger
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