Effectiveness of COVID-19 Vaccines against SARS-CoV-2 Omicron Variant (B.1.1.529): A Systematic Review with Meta-Analysis and Meta-Regression
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Abstract
Vaccine effectiveness (VE) and the urgency of booster vaccination against SARS-CoV-2 Omicron variant need evaluation. A systematic search was conducted from 1–6 April, 2022. VE difference (VED) estimates were assessed using random-effects and meta-regression analyses were performed for evaluating VE over time. Compared to full dose, booster dose of overall vaccines provided better protection against any and severe Omicron infections within 3 months (p < 0.001), and within 3 months or more in any, severe, and symptomatic infections (p < 0.001). From meta-regression analysis of overall vaccines, the full-dose VE against any and symptomatic Omicron infections reduced per month by 2.45% and 5.5%, respectively; whereas booster dose effectiveness against any and symptomatic Omicron infections reduced per month by 1.79% and 1.14%, respectively. The VE estimates of booster dose provide excellent protection against symptomatic infection compared to full dose. The VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 against Omicron infection are generally moderate, despite the VE estimates declining over time.
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Recent systematic review and meta-analyses reported that the third dose mRNA vaccines provided additional protection against the Omicron subvariant compared with the primary series or no vaccination, but the effectiveness waned over time.
“Similar to our findings, recent systematic review and meta-analyses20–22 reported that the third dose mRNA vaccines provided additional protection against the Omicron subvariant compared with the primary series or no vaccination, however, the effectiveness waned over time.”
From Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis (2023) · cites this paper as [21]
The Results (§3.3, page unavailable) report higher effectiveness for booster doses than for the primary series against Omicron, including in mRNA-vaccine analyses. The Abstract reports declining booster-effectiveness estimates over time, but the Discussion (§4, page unavailable) says the estimated reductions for booster doses were statistically insignificant. The claim presents waning effectiveness more definitively than this source supports. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNone of the published systematic reviews have assessed the magnitude and duration of protection conferred by booster doses of mRNA vaccines, particularly for the fourth dose, for a comprehensive range of COVID-19 outcomes caused by the Omicron subvariant and its sublineages.
“however, none have assessed the magnitude and duration of protection conferred by booster doses of mRNA vaccines, particularly for the fourth dose, for a comprehensive range of COVID-19 outcomes caused by the Omicron subvariant and its sublineages.”
From Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis (2023) · cites this paper as [21]
Experimental — accuracy not yet measuredSeveral systematic reviews of COVID-19 vaccine efficacy and effectiveness, with or without meta-analyses, have been published.
“Several systematic reviews of COVID-19 vaccine efficacy and effectiveness, with or without meta-analyses, have been published11 17–22”
From Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis (2023) · cites this paper as [21]
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Monge, S., Rojas‐Benedicto, A., Olmedo, C., Mazagatos, C., Sierra, M. J., Limia, A., Martín‐Merino, E., Larrauri, A., & Hernán, M. Á. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4035396 · Cited by 3 · see citing works
Flagged first, then by citations
1 of the 75 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [31]Lauring A.S. Tenforde M.W. Chappell J.D. Gaglani M. Ginde A.A. McNeal T. Ghamande S. Douin D.J. Talbot H.K. Casey J.D. Clinical Severity and MRNA Vaccine Effectiveness for Omicron, Delta, and Alpha SARS-CoV-2 Variants in the United States: A Prospective Observational Study medRxiv 2022 10.1101/2022.02.06.22270558 PMC8905308 35264324 · DOI
- [37]Young-Xu Y. Zwain G.M. Izurieta H.S. Korves C. Powell E.I. Smith J. Balajee MPH A.S. Holodniy M. Beenhouwer D.O. Rodriguez-Barradas M.C. Effectiveness of MRNA COVID-19 Booster Vaccines against Omicron and Delta Variants among US Veterans medRxiv 2022 10.1101/2022.01.15.22269360 PMC9352567 35922100 · DOI
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Terpos, E., Musto, P., Engelhardt, M. M., Delforge, M., Cook, G., Gay, F., van de Donk, N. W. C. J., Ntanasis‐Stathopoulos, I., Vangsted, A. J., Driessen, C., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01920-1 · Cited by 49 · see citing works
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Rahman, M. O., Kamigaki, T., Thandar, M. M., Haruyama, R., Yan, F., Shibamura-Fujiogi, M., Khin Maung Soe, J., Islam, M. R., Yoneoka, D., Miyahara, R., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2023-076892 · Cited by 29 · see citing works
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Joshi, K., Scholz, S. M., Maschio, M., Kohli, M. A., Lee, A., Fust, K., Ultsch, B., de Velde, N. V., & Beck, E. C. (2023) · Journal of Medical Economics · doi:10.1080/13696998.2023.2290388 · Cited by 16 · see citing works
Musto, P., Salmanton‐García, J., Sgherza, N., Bergantim, R., Farina, F., Glenthøj, A. B., Seval, G. C., Weinbergerová, B., Bonuomo, V., Bilgin, Y. M., et al. (2023) · Hematological Oncology · doi:10.1002/hon.3240 · Cited by 16 · see citing works
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Kohli, M. A., Maschio, M., Lee, A., Joshi, K., Carroll, S., Balogh, O., de Velde, N. V., & Beck, E. C. (2024) · Journal of Medical Economics · doi:10.1080/13696998.2024.2413288 · Cited by 10 · see citing works
Effectiveness of the monovalent XBB.1.5 COVID-19 vaccines: A systematic review and meta-analysis
Ma, H., Chen, Y.-Y., Shih, W., Chen, Y., Chen, T., & Fang, C. (2025) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2025.07.002 · Cited by 7 · see citing works
de Moraes, E. V., Pires, M. C., da Costa, A. C. R., Nunes, A. G. S., de Amorim, C. L., Manenti, E. R. F., Lucas, F. B., Rodrigues, F. D., Anschau, F., Fonseca, G., et al. (2024) · BMC Infectious Diseases · doi:10.1186/s12879-024-09865-1 · Cited by 6 · see citing works
Kohli, M. A., Maschio, M., Lee, A., Fust, K., de Velde, N. V., Buck, P. O., & Weinstein, M. C. (2022) · Journal of Medical Economics · doi:10.1080/13696998.2022.2126127 · Cited by 6 · see citing works
Krasner, H., Harmon, N., Martin, J. J., Olaco, C.-A., Netski, D. M., & Batra, K. (2024) · Vaccines · doi:10.3390/vaccines12020167 · Cited by 5 · see citing works
Intensive Care during the COVID-19 Pandemic
Wang, Y., Jin, Y., & Yang, H. (2023) · Vaccines · doi:10.3390/vaccines11010125 · Cited by 4 · see citing works
Meijerink, H., Veneti, L., Kristoffersen, A. B., Danielsen, A. S., Stecher, M., & Starrfelt, J. (2024) · BMC Public Health · doi:10.1186/s12889-024-19374-0 · Cited by 4 · see citing works
Smith, D. S., Postma, M. J., Fisman, D. N., & Mould-Quevedo, J. F. (2025) · Vaccine · doi:10.1016/j.vaccine.2025.126879 · Cited by 5 · see citing works
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- Authors
- Pratama, N. R., Wafa, I. A., Budi, D. S., Sutanto, H., Asmarawati, T. P., Barlian Effendi, G., & Wungu, C. D. K.
- Affiliations
- Universitas Airlangga (ID)
- Maastricht University (NL)
- Faculty of Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
- Corresponding author
- Wungu, Citrawati Dyah Kencono
- ORCID
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2022-12-19
- Volume
- 10
- Issue
- 12
- Pages
- 2180
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC9783108
- OpenAlex
- W4311884377
- Cited by
- 30
- References
- 75
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 2
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- 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
- COVID-19 vaccines, Omicron variant, vaccine effectiveness, booster vaccination, waning vaccine effectiveness, symptomatic infection, serious infections, Ad26.COV2-S, BNT162b2, ChAdOx1 nCoV-19 vaccine, mRNA-1273, time since vaccination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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