{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:27:30Z","timestamp":1788956850901,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002749","name":"Belgian Federal Science Policy Office","doi-asserted-by":"publisher","award":["LINK-VACC project"],"award-info":[{"award-number":["LINK-VACC project"]}],"id":[{"id":"10.13039\/501100002749","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons \u226518 years that had been fully vaccinated against COVID-19 for \u226514 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2\u201311.3)\/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52\u20131.56) or ChAdOx1 (HR1.68, 95%CI 1.66\u20131.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67\u20130.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23\u20130.24), as was an mRNA booster (HR0.44, 95%CI 0.43\u20130.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than na\u00efve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.<\/jats:p>","DOI":"10.3390\/v14040802","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T23:07:16Z","timestamp":1649891236000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-2202","authenticated-orcid":false,"given":"Veerle","family":"Stouten","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Hubin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freek","family":"Haarhuis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"van Loenhout","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-9242","authenticated-orcid":false,"given":"Matthieu","family":"Billuart","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-4150","authenticated-orcid":false,"given":"Ruben","family":"Brondeel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toon","family":"Braeye","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Van Oyen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"},{"name":"Department of Public Health and Primary Care, Ugent, 9000 Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Wyndham-Thomas","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4695-4275","authenticated-orcid":false,"given":"Lucy","family":"Catteau","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine","volume":"83","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK","volume":"397","author":"Voysey","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1056\/NEJMoa2101544","article-title":"Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19","volume":"384","author":"Sadoff","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s42269-021-00607-w","article-title":"A systematic review of effectiveness of BNT162b2 mRNA and ChAdOx1 adenoviral vector COVID-19 vaccines in the general population","volume":"45","author":"Iheanacho","year":"2021","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_6","first-page":"2100920","article-title":"Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: Second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021","volume":"26","author":"Harder","year":"2021","journal-title":"Eurosurveillance"},{"key":"ref_7","unstructured":"Catteau, L., van Loenhout, J., Stouten, V., Billuart, M., Hubin, P., Haarhuis, F., and Wyndham, T.C. (2021). Couverture Vaccinale et Impact \u00c9pid\u00e9miologique de la Campagne de Vaccination COVID-19 en Belgique, Sciensano. Available online: https:\/\/covid-19.sciensano.be\/sites\/default\/files\/Covid19\/COVID-19_THEMATIC_REPORT_VaccineCoverageAndImpactReport_FR.pdf."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sharma, A., Oda, G., and Holodniy, M. (2021). COVID-19 Vaccine Breakthrough Infections in the Veterans Health Administration. medRxiv.","DOI":"10.1101\/2021.09.23.21263864"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1473-3099(21)00460-6","article-title":"Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: A prospective, community-based, nested, case-control study","volume":"22","author":"Antonelli","year":"2022","journal-title":"Lancet Infect Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Peter, J.K., Wegner, F., Gsponer, S., Helfenstein, F., Roloff, T., Tarnutzer, R., Grosheintz, K., Back, M., Schaubhut, C., and Wagner, S. (2021). SARS-CoV-2 vaccine Alpha and Delta variant breakthrough infections are rare and mild, but happen relative early after vaccination. medRxiv.","DOI":"10.1101\/2021.12.23.21268324"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fisman, D.N., Lee, N., and Tuite, A.R. (2022). Timing of Breakthrough Infection Risk After Vaccination Against SARS-CoV-2. medRxiv.","DOI":"10.1101\/2022.01.04.22268773"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Uschner, D., Bott, M., Santacatterina, M., Gunaratne, M., Fette, L.M., Burke, B., Strylewicz, G., Edelstein, S.L., Lagarde, W.H., and Miller, K. (2021). Breakthrough SARS-CoV-2 Infections after Vaccination in North Carolina. medRxiv.","DOI":"10.1101\/2021.10.10.21264812"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, C., Lee, J., Ta, C., Soroush, A., Rogers, J.R., Kim, J.H., Natarajan, K., Zucker, J., and Weng, C. (2021). A Retrospective Analysis of COVID-19 mRNA Vaccine Breakthrough Infections\u2014Risk Factors and Vaccine Effectiveness. medRxiv.","DOI":"10.1101\/2021.10.05.21264583"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s13690-021-00709-x","article-title":"Conceptual causal framework to assess the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients","volume":"79","author":"Serrien","year":"2021","journal-title":"Arch. Public Health"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Proesmans, K., Hancart, S., Braeye, T., Klamer, S., Robesyn, E., Djiena, A., De Leeuw, F., Mahieu, R., Dreuw, A., and Hammami, N. (2022, March 07). COVID-19 Contact Tracing in Belgium: Main Indicators and Performance, January\u2013September 2021. Available online: https:\/\/www.researchsquare.com\/article\/rs-1326456\/v1.","DOI":"10.1186\/s13690-022-00875-6"},{"key":"ref_16","unstructured":"(2022, February 10). COVID-19\u2014Gevalsdefinitie en Testing|Coronavirus COVID-19. Available online: https:\/\/covid-19.sciensano.be\/nl\/covid-19-gevalsdefinitie-en-testing."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Braeye, T., Catteau, L., Brondeel, R., van Loenhout, J., Proesmans, K., Cornelissen, L., Van Oyen, H., Stouten, V., Hubin, P., and Billuart, M. (2022). Vaccine Effectiveness against COVID19-Infection and Onward Transmission by Variant of Concern and Time Since Vaccination, Belgian Contact Tracing, 2021, Social Science Research Network. Available online: https:\/\/papers.ssrn.com\/abstract=4000559.","DOI":"10.2139\/ssrn.4000559"},{"key":"ref_18","unstructured":"(2022, January 11). Population Movement|Statbel. Available online: https:\/\/statbel.fgov.be\/en\/themes\/population\/population-movement."},{"key":"ref_19","unstructured":"Green, A.C., Curtis, H.J., Hulme, W.J., Williamson, E.J., McDonald, H.I., Bhaskaran, K., Rentsch, C., Schultze, A., MacKenna, B., and Mahalingasivam, V. (2021). Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY. medRxiv."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Israel, A., Merzon, E., Sch\u00e4ffer, A.A., Shenhar, Y., Green., I., Golan-Cohen, A., Ruppin, E., Magen, E., and Vinker, S. (2021). Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort. medRxiv.","DOI":"10.1101\/2021.08.03.21261496"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Reynolds, M.W., Xie, Y., Knuth, K.B., Mack, C.D., Brinkley, E., Toovey, S., and Dreyer, N.A. (2022). COVID-19 vaccination breakthrough infections in a real-world setting: Using community reporters to evaluate vaccine effectiveness. medRxiv.","DOI":"10.1101\/2022.01.11.22268736"},{"key":"ref_22","unstructured":"Stouten, V., Blot, K., Haarhuis, F., Serrien, B., Hubin, P., Vandromme, M., Litzroth, A., Chung, J., Billuart, M., and Van Goethem, N. (2021). Occurrence and Patient Characteristics of COVID-19 Breakthrough Infections, Sciensano."},{"key":"ref_23","first-page":"e19102","article-title":"Equivalency of Protection from Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis","volume":"10","author":"Shenai","year":"2021","journal-title":"Cureus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.15585\/mmwr.mm7032e1","article-title":"Reduced Risk of Reinfection with SARS-CoV-2 after COVID-19 Vaccination\u2014Kentucky, May\u2013June 2021","volume":"70","author":"Cavanaugh","year":"2021","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gazit, S., Shlezinger, R., Perez, G., Lotan, R., Peretz, A., Ben-Tov, A., Herzel, E., Alapi, H., Cohen, D., and Muhsen, K. (2022). The Incidence of SARS-CoV-2 Reinfection in Persons with Naturally Acquired Immunity with and without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine. Ann. Intern. Med.","DOI":"10.7326\/M21-4130"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1126\/science.abm0620","article-title":"SARS-CoV-2 vaccine protection and deaths among US veterans during 2021","volume":"375","author":"Cohn","year":"2022","journal-title":"Science"},{"key":"ref_27","first-page":"e2132540","article-title":"Analysis of the Effectiveness of the Ad26.COV2.S Adenoviral Vector Vaccine for Preventing COVID-19","volume":"11","author":"Zemmour","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_28","first-page":"e92","article-title":"Effectiveness of COVID-19 vaccines against the B.1.617.2 (Delta) variant","volume":"385","author":"Bernal","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bernal, J.L., Andrews, N., Gower, C., Stowe, J., Tessier, E., Simmons, R., and Ramsay, M. (2021). Effectiveness of BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on mortality following COVID-19. medRxiv.","DOI":"10.1101\/2021.05.14.21257218"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cohn, B.A., Cirillo, P.M., Murphy, C.C., Krigbaum, N.Y., and Wallace, A.W. (2021). Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021. medRxiv.","DOI":"10.1101\/2021.10.13.21264966"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kshirsagar, M., Mukherjee, S., Nasir, M., Becker, N., Ferres, J.L., and Richardson, B.A. (2021). Risk of hospitalization and mortality after breakthrough SARS-CoV-2 infection by vaccine type and previous SARS-CoV-2 infection utilizing medical claims data. medRxiv.","DOI":"10.1101\/2021.12.08.21267483"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"W\u00fcrtz, A.M., Kinnerup, M.B., Pugdahl, K., Schl\u00fcnssen, V., Vestergaard, J.M., Nielsen, K., Cramer, C., Bonde, J.P., Biering, K., and Carstensen, O. (2022). Healthcare workers\u2019 SARS-CoV-2 infection rates during the second wave of the pandemic: Prospective follow-up study. medRxiv.","DOI":"10.1101\/2021.11.17.21266459"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:53:19Z","timestamp":1760136799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["v14040802"],"URL":"https:\/\/doi.org\/10.3390\/v14040802","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]}}}