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. 2025 May 6;20(5):e0320434.
doi: 10.1371/journal.pone.0320434. eCollection 2025.

Effectiveness over time of a primary series of the original monovalent COVID-19 vaccines in adults in the United States

J Bradley Layton  1 , Patricia C Lloyd  2 , Lauren S Peetluk  3 , Yixin Jiao  4 , Djeneba Audrey Djibo  5 , Joann F Gruber  2 , Jie Deng  3 , Christine Bui  1 , An-Chi Lo  4 , Rachel P Ogilvie  3 , Ron Parambi  3 , Michael Miller  3 , Jennifer Song  3 , Lisa B Weatherby  3 , Sylvia Cho  2 , Hui Lee Wong  2 , Tainya C Clarke  2 , Jessica Rose Hervol  4 , Dóra Illei  6 , Elizabeth J Bell  3 , Grace Wenya Yang  7 , John D Seeger  3 , Michael Wernecke  4 , Morgan M Richey  1 , Richard A Forshee  2 , Steven A Anderson  2 , Yoganand Chillarige  4 , Cheryl N McMahill-Walraven  5 , Kandace L Amend  3 , Mary S Anthony  1 , Azadeh Shoaibi  2
Affiliations

Effectiveness over time of a primary series of the original monovalent COVID-19 vaccines in adults in the United States

J Bradley Layton et al. PLoS One. .

Abstract

With data from 2 US claims databases (Optum, CVS Health) supplemented with Immunization Information System COVID-19 vaccine records, we evaluated overall and time-specific vaccine effectiveness (VE) of an initial primary series for 3 monovalent COVID-19 vaccines-BNT162b2, mRNA-1273, and JNJ-7836735-in adults (18-64 years). Vaccinated individuals were matched to unvaccinated comparators, and we estimated VE against any medically diagnosed COVID-19 and hospital/emergency department (ED)-diagnosed COVID-19. Additionally, we estimated VE by era of predominant variants, in subgroups, and compared across vaccine brands. The cohorts consisted of 341,097 (Optum) and 1,151,775 (CVS Health) matched pairs for BNT162b2; 201,604 (Optum) and 651,545 (CVS Health) for mRNA-1273; and 49,285 (Optum) and 149,813 (CVS Health) for JNJ-7836735. The study period began 11 December 2020 (date of first COVID-19 vaccine availability in the US) and ended 15 January 2022 in Optum and 31 March 2022 in CVS Health. Summary VE estimates from meta-analysis against hospital/ED-diagnosed COVID-19 were: BNT162b2, 77% (95% CI, 76%-78%); mRNA-1273, 84% (95% CI, 83%-85%), JNJ-7836735 66% (95% CI, 63%-68%). VE estimates were higher for hospital/ED-diagnosed COVID-19 than for medically diagnosed COVID-19, and VE estimates were highest in adults receiving mRNA-1273 for both outcomes. VE was sustained for approximately 7 months for medically diagnosed and up to 9 months for hospital/ED-diagnosed COVID-19. VE differed by brand and variant era. Ongoing real-world surveillance of COVID-19 vaccines using robust data sources and methodology is needed as new variants and recommendations for updated vaccines have evolved.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: JBL, CB, DI, MMR, and MSA are employees of RTI International, an independent, nonprofit research institute that performs research on behalf of governmental and commercial clients, including vaccine manufacturers. LP, JD, RO, RP, MM, JS, LBW, GWY, JS, and KA are employees of Optum and own stock in UnitedHealth Group. EJB is an employee of Optum. DAD and CNMW are employees of CVS Health. The other authors have no conflicts to report.

Figures

Fig 1
Fig 1. Patterns of Primary Series Completion for 2-Dose and 1-Dose COVID-19 Vaccines.
COVID-19 =  coronavirus disease 2019, a Day 17 for BNT162b2, day 24 for mRNA-1273.
Fig 2
Fig 2. Schematic for Assessing Eligibility, Covariates, and COVID-19 Outcomes Among Vaccinated Individuals and Matched Unvaccinated Comparators.
COVID-19 = coronavirus disease 2019; ED = emergency department; LTC = long-term care. Note: Use of “all available” data indicates that the entire duration of an individual’s available continuous enrollment information before Time 0, back to the beginning of data availability (1 December 2017), was used; the duration of available data was at least 365 days, but may vary for each individual. a Gaps in medical and pharmacy coverage < 32 days permitted. b Date of first COVID-19 vaccine authorization in the US. c Hospitalization or long-term care residence at Time 0. d COVID-19 monoclonal antibodies or convalescent plasma. e Diagnoses of general acute symptoms (fever, nausea/vomiting, rash) and healthcare utilization (hospitalization, ED visit) serving as an indicator of health status at the time of vaccination. f Number of hospitalizations, number of ED visits, skilled nursing facility stay, influenza vaccination, pneumococcal vaccination, encounter for cancer screening, eye examination, colonoscopy, bone mineral density test, well-check/well-child preventive healthcare visit, arthritis, lipid abnormality, ambulance use/life support service, weakness, pregnancy completion before Time 0. g Autoimmune disorders, cancer, chronic kidney disease or renal disease, chronic liver disease, chronic lung diseases (e.g., asthma, chronic obstructive pulmonary disease [COPD], cystic fibrosis, pulmonary embolism), dementia or other neurological conditions, diabetes mellitus type 1 or 2, Down syndrome, heart conditions (e.g., heart failure, coronary artery disease, arrhythmias), hypertension, immunocompromised state, mental health conditions, obese or severely obese, sickle cell disease or thalassemia, stroke or cerebrovascular disease, tuberculosis, COVID-19 laboratory test performed (binary indicator of any test performed or none), COVID-19 diagnoses. h End of study period, end of continuous health plan enrollment, relocation out of study area, deviation from the categorized vaccine exposure status.
Fig 3
Fig 3. Estimated Effectiveness of Receiving a Complete Primary Series of COVID-19 Vaccines Compared With Being Unvaccinated in Adults Aged 18-64 Years.
CI =  confidence interval; ED =  emergency department; VE =  vaccine effectiveness. a Indicates evidence of statistical heterogeneity between data source–specific estimates, p < 0.05.
Fig 4
Fig 4. Estimated Effectiveness Over Time of Receiving a Complete Primary Series of COVID-19 Vaccines Compared With Being Unvaccinated in Adults Aged 18-64 Years.
COVID-19 = coronavirus disease 2019; ED = emergency department.
See this image and copyright information in PMC

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