Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study
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Abstract
OBJECTIVES: To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. DESIGN: Test negative case-control study. SETTING: Kaiser Permanente Southern California (KPSC), an integrated healthcare system. PARTICIPANTS: Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. INTERVENTIONS: Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. MAIN OUTCOME MEASURES: Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1-odds ratio)×100%. RESULTS: The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. CONCLUSIONS: Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.
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Vaccine effectiveness declines over time, as shown in several observational studies.
“This led to a decline in vaccine effectiveness (VE) over time, as shown in several observational studies [2, 3].”
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Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants
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“This led to a decline in vaccine effectiveness (VE) over time, as shown in several observational studies [2, 3].”
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- Authors
- Bruxvoort, K. J., Sy, L. S., Qian, L., Ackerson, B. K., Luo, Y., Lee, G. S., Tian, Y., Florea, A., Aragones, M., Tubert, J. E., Takhar, H. S., Ku, J. H., Paila, Y. D., Talarico, C. A., & Tseng, H. F.
- Affiliations
- Kaiser Permanente (US)
- Moderna Inc, Cambridge, MA 02139, USA
- Corresponding author
- Bruxvoort, Katia J
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2021-12-15
- Volume
- 375
- Pages
- e068848
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC8671836
- OpenAlex
- W4200126619
- Cited by
- 230
- References
- 44
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 26 · 2023: 52 · 2022: 122 · 2021: 11 · 2013: 1
- FWCI
- 16.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ (publishedVersion, cc-by-nc)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Pfizer
- GlaxoSmithKline
- Gilead Sciences
- Moderna
- Seqirus
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- mRNA-1273 vaccine, SARS-CoV-2 variants, Delta variant, Mu variant, vaccine effectiveness, waning vaccine effectiveness, time since vaccination, COVID-19 hospitalization, COVID-19 infection, Alpha variant, older adults, test-negative design, whole genome sequencing, Moderna vaccine, Kaiser Permanente Southern California, integrated care
- MeSH terms
- COVID-19, SARS-CoV-2, Vaccine Efficacy, 2019-nCoV Vaccine mRNA-1273, Adolescent, Adult, Aged, California, Female, Hospitalization, Humans, Male, Middle Aged, Vaccination, Case-Control Studies, Young Adult
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