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Abstract
Objectives The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.
Design Systematic review and meta-analysis.
Data sources Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.
Study eligibility criteria We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.
Data extraction and synthesis Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.
Results This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14–30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61–90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91–120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.
Conclusion The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.
PROSPERO registration number CRD42023376698.
- COVID-19
- systematic review
- meta-analysis
- vaccination
- SARS-CoV-2 infection
Data availability statement
Data are available on reasonable request. All data included were derived from publicly available evidence cited in the references. Extracted data are available on request to the corresponding author.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Data availability statement
Data are available on reasonable request. All data included were derived from publicly available evidence cited in the references. Extracted data are available on request to the corresponding author.
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Footnotes
Contributors MOR and TK conceptualised the review. MOR, TK and EO designed the review protocol. MOR developed search strategy and performed electronic database searching. MOR, FY, MMT, RH, MRI, JKMS, MS-F and TK carried out the literature search and data collection. MOR did the formal data analysis. TK, EO, RM, DY and MS validated the analytical results. MOR and EO performed risk of bias assessment in the included studies and grading the certainty of evidence. MOR wrote the original draft, and had access to the data and full responsibility of conducting and publishing the review. All authors contributed to data interpretation, reviewing and editing this manuscript.
Funding This research was supported in part by grants from the Ministry of Health, Labour and Welfare, Japan (funding number: 23HA2005 and 23HA2017).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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