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The study investigated the cumulative incidence of SARS-CoV-2 BI after booster dose and its correlation with age, sex, job title, previous infection, and time since third dose.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged\u2009&lt;\u200950\u00a0years, but nearly halved after 60\u00a0years. Nurses experienced the highest BI incidence, and administrative staff experienced the lowest. The BI incidence was higher in immunosuppressed HW (28.6%) vs others (24.9%). When controlling for gender, age, job title and infection before booster, heterologous vaccination reduced BI incidence with respect to the BNT162b2 mRNA vaccine [Odds Ratio (OR) 0.69, 95% CI 0.63\u20130.76]. Previous infection protected against asymptomatic infection [Relative Risk Ratio (RRR) of recent infection vs no infection 0.53, 95% CI 0.23\u20131.20] and even more against symptomatic infections [RRR 0.11, 95% CI 0.05\u20130.25]. Symptomatic infections increased from 70.5% in HW receiving the booster dose since\u2009&lt;\u200964\u00a0days to 86.2% when time elapsed was\u2009&gt;\u2009130\u00a0days.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The risk of BI after booster is significantly reduced by previous infection, heterologous vaccination, and older ages. Immunosuppression is relevant for increased BI incidence. Time elapsed from booster affects BI severity, confirming the public health usefulness of booster. Further research should focus on BI trend after 4th dose and its relationship with time variables across the epidemics.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s44197-023-00139-8","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T13:01:35Z","timestamp":1690030895000},"page":"577-588","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Incidence and Determinants of Symptomatic and Asymptomatic SARS-CoV-2 Breakthrough Infections After Booster Dose in a Large European Multicentric Cohort of Health Workers-ORCHESTRA Project"],"prefix":"10.1007","volume":"13","author":[{"given":"Stefano","family":"Porru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia 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The study was approved (No.436 14 October 2021) by the Italian Medicine Agency (AIFA) and the Ethics Committee of the Italian National Institute of Infectious Diseases (INMI) Lazzaro Spallanzani. All the cohorts collected loco-regional ethical approvals. All participants signed informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}