{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:27:39Z","timestamp":1768868859385,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Johnson &amp; Johnson Innovative Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: COVID-19 vaccines have significantly reduced the mortality and morbidity associated with SARS-CoV-2. In the fall of 2021, the U.S. Food and Drug Administration amended its emergency use authorization guidelines for COVID-19 vaccines to allow the administration of booster vaccine doses based on sound scientific evidence of the increase in effectiveness conferred by boosters. The effectiveness of the Ad26.COV2.S COVID-19 booster vaccine during the periods of Delta and Omicron variant dominance is unknown. This study used real-world data to estimate the effectiveness of booster heterologous or homologous Ad26.COV2.S vaccination compared to that of a primary Ad26.COV2.S or mRNA COVID-19 vaccination series. Methods: A retrospective, observational, longitudinal cohort study design was used with a total eligible sample population consisting of 72,461,026 individuals in the HealthVerity dataset. The study cohort consisted of individuals \u226518 years in the United States with evidence of a COVID-19 primary vaccination series (Ad26.COV2.S or mRNA) administered between 1 January 2021 and 6 July 2022. Two exposure groups were considered based on retrospective database classification: a heterologous Ad26.COV2.S booster and a homologous Ad26.COV2.S booster. Individuals eligible for the referent groups, defined as those with a primary vaccine series alone, were identified through exact matching by age, sex, time since primary series vaccine, location, and Gagne comorbidity score. Propensity score-matched Cox proportional hazards models were used to evaluate outcomes, including COVID-19-related hospitalization and medically attended COVID-19. Results: Depending on the comparison group of interest, the adjusted hazard ratios for COVID-19-related hospitalization ranged from 0.63 (95% CI: 0.56, 0.72) to 0.82 (95% CI: 0.75, 0.90), and 0.93 (95% CI: 0.90, 0.96) to 0.94 (95% CI: 0.91, 0.97) for medically attended COVID-19, both favoring booster vaccination. Conclusions: The results of this study demonstrate the effectiveness of an Ad26.COV2.S booster vaccination compared to primary series vaccination in preventing COVID-19 hospitalization and medically attended COVID-19 for at least 12 months. This study adds to the scientific evidence that demonstrates the importance of COVID-19 booster vaccinations to support public health policy.<\/jats:p>","DOI":"10.3390\/vaccines13020166","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness of Heterologous and Homologous Ad26.COV2.S Vaccine Boosting in Preventing COVID-19-Related Outcomes Among Individuals with a Completed Primary Vaccination Series in the United States"],"prefix":"10.3390","volume":"13","author":[{"given":"Mawuli","family":"Nyaku","sequence":"first","affiliation":[{"name":"Johnson & Johnson Innovative Medicine, Data Science and Digital Health, Spring House, PA 19002, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara S.","family":"Yoon","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Ricci","sequence":"additional","affiliation":[{"name":"Johnson & Johnson Innovative Medicine, Data Science and Digital Health, Spring House, PA 19002, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lexie","family":"Rubens","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Iyer","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Zhen","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-519X","authenticated-orcid":false,"given":"Raymond A.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Johnson & Johnson Innovative Medicine, Data Science and Digital Health, Spring House, PA 19002, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Madsen","sequence":"additional","affiliation":[{"name":"Aetion Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2220385","DOI":"10.1001\/jamanetworkopen.2022.20385","article-title":"Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths Prevented Among Vaccinated Persons in the US, December 2020 to September 2021","volume":"5","author":"Steele","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yamana, T.K., Galanti, M., Pei, S., Di Fusco, M., Angulo, F.J., Moran, M.M., Khan, F., Swerdlow, D.L., and Shaman, J. (2023). The Impact of COVID-19 Vaccination in the US: Averted Burden of SARS-CoV-2-Related Cases, Hospitalizations and Deaths. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0275699"},{"key":"ref_3","unstructured":"(2024, February 15). Authorizations of Emergency Use of Certain Biological Products During the COVID-19 Pandemic Availability, Available online: https:\/\/www.federalregister.gov\/documents\/2021\/05\/27\/2021-11234\/authorizations-of-emergency-use-of-certain-biological-products-during-the-covid-19-pandemic."},{"key":"ref_4","unstructured":"(2025, January 03). Vaccine Monitor: Eagerness to Get Vaccinated Begins to Level Off as Most People Who Want a Vaccine Have Gotten One, but Republicans Show Biggest Shift Toward Vaccination. KFF. Available online: https:\/\/www.kff.org\/coronavirus-covid-19\/press-release\/vaccine-monitor-eagerness-to-get-vaccinated-begins-to-level-off-as-most-people-who-want-a-vaccine-have-gotten-one-but-republicans-show-biggest-shift-toward-vaccination\/."},{"key":"ref_5","unstructured":"CDC (2021, November 08). COVID Data Tracker, Available online: https:\/\/covid.cdc.gov\/covid-data-tracker."},{"key":"ref_6","unstructured":"(2025, January 27). Coronavirus (COVID-19) Update: FDA Expands Eligibility for COVID-19 Vaccine Boosters, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-expands-eligibility-covid-19-vaccine-boosters."},{"key":"ref_7","unstructured":"(2024, February 15). Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised."},{"key":"ref_8","unstructured":"(2024, February 15). Coronavirus (COVID-19) Update: 29 October 2021, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-october-29-2021."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0140-6736(21)01420-3","article-title":"Immunogenicity and Reactogenicity of BNT162b2 Booster in ChAdOx1-S-Primed Participants (CombiVacS): A Multicentre, Open-Label, Randomised, Controlled, Phase 2 Trial","volume":"398","author":"Borobia","year":"2021","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing Antibody Levels Are Highly Predictive of Immune Protection from Symptomatic SARS-CoV-2 Infection","volume":"27","author":"Khoury","year":"2021","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/S1473-3099(22)00506-0","article-title":"Efficacy, Safety, and Immunogenicity of a Booster Regimen of Ad26.COV2.S Vaccine against COVID-19 (ENSEMBLE2): Results of a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial","volume":"22","author":"Hardt","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMoa2116414","article-title":"Homologous and Heterologous COVID-19 Booster Vaccinations","volume":"386","author":"Atmar","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_13","unstructured":"(2025, January 03). Vaccines and Related Biological Products Advisory Committee 14\u201315 October 2021 Meeting Presentation. Presented at the Vaccines and Related Biological Products Advisory Committee Meeting, Available online: https:\/\/www.fda.gov\/advisory-committees\/advisory-committee-calendar\/vaccines-and-related-biological-products-advisory-committee-october-14-15-2021-meeting-announcement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"ofad288","DOI":"10.1093\/ofid\/ofad288","article-title":"Relative Effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines and Homologous Boosting in Preventing COVID-19 in Adults in the US","volume":"10","author":"Boileau","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S2213-2600(23)00015-2","article-title":"Long-Term Effectiveness of COVID-19 Vaccines against Infections, Hospitalisations, and Mortality in Adults: Findings from a Rapid Living Systematic Evidence Synthesis and Meta-Analysis up to December, 2022","volume":"11","author":"Wu","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e072065","DOI":"10.1136\/bmj-2022-072065","article-title":"Vaccine Effectiveness of Primary Series and Booster Doses against COVID-19 Associated Hospital Admissions in the United States: Living Test Negative Design Study","volume":"379","author":"Adams","year":"2022","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ofac698","DOI":"10.1093\/ofid\/ofac698","article-title":"Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021\u2013April 2022","volume":"10","author":"Lewis","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_18","unstructured":"(2025, January 02). Table HIC-4_ACS. Health Insurance Coverage Status and Type of Coverage by State\u2014All Persons: 2008 to 2019, September 2020, Available online: https:\/\/www.census.gov\/library\/publications\/2023\/demo\/p60-281.html."},{"key":"ref_19","unstructured":"Centers for Disease Control and Prevention (2024, December 06). Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Pfizer-BioNTech, Moderna, and Janssen COVID-19 Booster Doses, Available online: https:\/\/www.cdc.gov\/acip\/grade\/covid-19-booster-doses.html#:~:text=COV2.S%20Vaccine%20(5%C3%971010%20viral%20particles%2C%20IM)%20should,%E2%89%A518%20years%20who%20completed%20a%20COVID%2D19%20vaccine."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jclinepi.2010.10.004","article-title":"A Combined Comorbidity Score Predicted Mortality in Elderly Patients Better than Existing Scores","volume":"64","author":"Gagne","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression Models and Life-Tables","volume":"34","author":"Cox","year":"1972","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_22","unstructured":"Rothman, K.J., Lash, T.L., VanderWeele, T.J., and Haneuse, S. (2021). Modern Epidemiology, Wolters Kluwer. [4th ed.]."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/2\/166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:54Z","timestamp":1760027394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/2\/166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,9]]},"references-count":22,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["vaccines13020166"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13020166","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,9]]}}}