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Meta-Analysis
. 2025 Jan 3;119(1):1-12.
doi: 10.1093/trstmh/trae082.

How well do different COVID-19 vaccines protect against different viral variants? A systematic review and meta-analysis

Thi Ngoc Anh Hoang  1 , Aisling Byrne  2 , Ha-Linh Quach  2   3 , Melanie Bannister-Tyrrell  4 , Florian Vogt  2   5
Affiliations
Meta-Analysis

How well do different COVID-19 vaccines protect against different viral variants? A systematic review and meta-analysis

Thi Ngoc Anh Hoang et al. Trans R Soc Trop Med Hyg. .

Abstract

While the efficacy of coronavirus disease 2019 (COVID-19) vaccines has been evaluated in numerous trials, comprehensive evidence on how protection by different vaccines has varied over time remains limited. We aimed to compare protective effects of different vaccines against different viral variants. To achieve this, we searched Medline, Cochrane Library and Embase for randomized controlled trials assessing the efficacy of COVID-19 vaccines. Forest plots using Mantel-Haenszel and random-effects models were generated showing risk ratios (RRs) and 95% CIs by vaccines and variants. We included 36 studies with 90 variant-specific primary outcomes. We found a RR of 0.26 (95% CI 0.21 to 0.31) against all variants overall, with the highest protective effects against the wild-type (RR 0.13; 95% CI 0.10 to 0.18), followed by Alpha (RR 0.26; 95% CI 0.18 to 0.36), Gamma (RR 0.34; 95% CI 0.21 to 0.55), Delta (RR 0.39; 95% CI 0.28 to 0.56) and Beta (RR 0.49; 95% CI 0.40 to 0.62) variants. Nucleic acid vaccines showed the highest protection levels against all variants (RR 0.11; 95% CI 0.08 to 0.15), followed by protein subunit, inactivated virus and viral vector. In conclusion, we found high but heterogenous levels of protection for most COVID-19 vaccines, with decreasing protective effects for vaccines based on traditional technologies as SARS-CoV-2 variants emerged over time. Novel nucleic acid-based vaccines offered substantially higher and more consistent protection.

Keywords: COVID-19 vaccine efficacy; meta-analysis; systematic review; viral variants.

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Conflict of interest statement

All authors declare that they have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Selection of included studies and outcomes from search results. RCT, randomized controlled trial; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 2.
Figure 2.
Risk ratios (RRs) of all included outcomes (n=90) by viral variant. Diamonds represent overall pooled estimates. Weights and between-subgroup heterogeneity were derived from random-effects models. Note: the common effect model is the Mantel–Haenszel model.
Figure 3.
Figure 3.
Risk ratios (RRs) of all included outcomes (n=90) by vaccine type. Diamonds represent overall pooled estimates. Weights and between-subgroup heterogeneity were derived from random-effects models. Note: the common effect model is the Mantel–Haenszel model.
Figure 4.
Figure 4.
(A–F) Risk ratios of all included outcomes (n=90) by vaccine brand for each viral variant. Red diamonds represent overall pooled estimates. The missing p-value is because no pooled analysis was conducted due to the presence of only one study in this group.
Figure 4.
Figure 4.
(A–F) Risk ratios of all included outcomes (n=90) by vaccine brand for each viral variant. Red diamonds represent overall pooled estimates. The missing p-value is because no pooled analysis was conducted due to the presence of only one study in this group.
Figure 4.
Figure 4.
(A–F) Risk ratios of all included outcomes (n=90) by vaccine brand for each viral variant. Red diamonds represent overall pooled estimates. The missing p-value is because no pooled analysis was conducted due to the presence of only one study in this group.
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