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SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: a systematic review and meta-analysis
Open accessAbstract
Background: The temporal evolution of SARS-CoV-2 vaccine efficacy and effectiveness (VE) against infection, symptomatic, and severe COVID-19 is incompletely defined. The temporal evolution of VE could be dependent on age, vaccine types, variants of the virus, and geographic region. We aimed to conduct a systematic review and meta-analysis of the duration of VE against SARS-CoV-2 infection, symptomatic COVID-19 and severe COVID-19. Methods: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched and studies were selected. Independent reviewers selected randomized controlled trials and cohort studies with the outcome of interest. Independent reviewers extracted data, and assessed the risk of bias. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Primary outcomes included VE as a function of time against SARS-CoV-2 infection, symptomatic and severe COVID-19. Results: Eighteen studies were included representing nearly 7 million individuals. VE against all SARS-CoV-2 infections declined from 83% in the first month after completion of the original vaccination series to 22% at 5 months or longer. Similarly, VE against symptomatic COVID-19 declined from 94% in the first month after vaccination to 64% by the fourth month. VE against severe COVID-19 for all ages was high overall, with the level being 90% (95% CI, 87–92%) at five months or longer after being fully vaccinated. VE against severe COVID-19 was lower in individuals ≥ 65 years and those who received Ad26.COV2.S. Conclusions: VE against SARS-CoV-2 infection and symptomatic COVID-19 waned over time but protection remained high against severe COVID-19. These data can be used to inform public health decisions around the need for booster vaccination.
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![Fig. 2 Scatterplot of Vaccine efficacy/effectiveness (VE) % against SARS-CoV-2 infection (A), symptomatic COVID-19 (B) and severe COVID-19 (C) plotted according to time from the second dose for mRNA vaccines and one dose of adenovirus vector-based vaccine. Each circle represents a study, and its size is proportional to the study’s sample size and annotated according to vaccine type. Effectiveness estimates include studies that estimated efficacy. The red line represents the fitted mean VE using the natural cubic spline model. The horizontal blue line represents the 50% protection level stipulated by the WHO [7]](/paper-figures/06e0442577404df6b2de16ef82ef0a8d/sars-cov-2-vaccine-effectiveness-against-infection-symptomatic-and-severe-covid-figure-2.jpg)

![Fig. 4 Scatterplot of Vaccine efficacy/effectiveness (VE) against infection and severe disease stratified by age. VE against infection in subjects < 65 years (A) ≥ 65 years (B), against severe COVID-19 disease in those < 65 years (C) and ≥ 65 years (D) plotted according to time since full vaccination (14 days after second dose for mRNA vaccines and after one dose of adenovirus vector-based vaccine). Each circle represents a study, and its size is proportional to the study’s sample size and annotated according to vaccine type. The red line represents the fitted mean VE using the natural cubic spline model. The horizontal blue line represents the 50% protection level stipulated by the WHO [7]](/paper-figures/ed09a5e043df4e83b26234e7238ff6e5/sars-cov-2-vaccine-effectiveness-against-infection-symptomatic-and-severe-covid-figure-4.jpg)


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“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 [17]
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“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 [17]
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Metadata
- Authors
- Ssentongo, P., Ssentongo, A. E., Voleti, N., Groff, D., Sun, A., Ba, D. M., Nunez, J., Parent, L. J., Chinchilli, V. M., & Paules, C. I.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Ssentongo, Paddy
- ORCID
- Venue
- BMC Infectious Diseases
- Published
- 2022-05-07
- Volume
- 22
- Issue
- 1
- Pages
- 439-439
- ISSN
- 1471-2334 (ISSN-L)
- PMC
- PMC9077344
- OpenAlex
- W4229081322
- Cited by
- 260
- References
- 39
- Citations by year
- 2026: 18 · 2025: 36 · 2024: 66 · 2023: 98 · 2022: 42
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Infectious Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, COVID-19 vaccines, vaccine effectiveness, waning immunity, duration of protection, symptomatic COVID-19, severe COVID-19, Ad26.COV2-S, booster vaccination, older adults
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Vaccine Efficacy, Ad26COVS1, Child, Humans
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