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
Stefano Porru, Maria Grazia Lourdes Monaco, Gianluca Spiteri, Angela Carta, Gulser Caliskan, Concepción Violán, Pere Torán‐Monserrat, Luigi Vimercati, Silvio Tafuri, Paolo Boffetta, Francesco Saverio Violante, Emma Sala, Emanuele Sansone, Fabriziomaria Gobba, Loretta Casolari, Andreas Wieser, Christian Janke, Adonina Tardón, Marta María Rodríguez-Suárez, Filippo Liviero, Maria Luisa Scapellato, Marco Dell’Omo, Nicola Murgia, Dana Mateș, Violeta Claudia Calota, Jozef Strhársky, M Mrázová, Enrico Pira, Alessandro Godono, Greta Camilla Magnano, Corrado Negro, Giuseppe Verlato, Orchestra WP5 Working Group, Maria Diletta Pezzani, Evelina Tacconelli, Davide Gibellini, Virginia Lotti, Lucí Amalia Carrasco-Ribelles, Eva María Martínez Cácers, Julia Garcia Prado, Noemí Lamonja-Vicente, Luigi De Maria, Pasquale Stefanizzi, Stefania Sponselli, Antonio Caputi, Mahsa Abedini, Giorgia Ditano, Shuffield S. Asafo, Giulia Collatuzzo, Giuseppe De Palma, Alberto Modenese, Giorgia Rossi, Francesca Glieca, Daniela Vivoli, Michael Hoelscher, Noemi Castelletti, Christina Reinkemeyer, Thu Giang Le Thi, Guillermo Fernandez-Tardon, Pedro Ignacio Arcos-Gonzalez, Francisco José Jimeno-Demuth, Carmen Natal-Ramos, Angelo Moretto, Paola Mason, Sofia Pavanello, Anna Volpin, Giacomo Muzi, Angela Gambelunghe, Ilenia Folletti, Tiziana Fiordi, Andra Neamtu, Ovidiu Perseca, Catalin Alexandru Staicu, Angelica Voinoiu, Eleonóra Fabiánová, Roman Nedela, Jana Oravec Bérešová, Lenka Palcová, Ihab Mansour, Catalina Ciocan, Andrea Franceschi, Francesca Larese Filon, Luca Cegolon
Abstract
BACKGROUND: SARS-CoV-2 breakthrough infections (BI) after vaccine booster dose are a relevant public health issue. METHODS: Multicentric longitudinal cohort study within the ORCHESTRA project, involving 63,516 health workers (HW) from 14 European settings. 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. RESULTS: 13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged < 50 years, but nearly halved after 60 years. 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 0.63-0.76]. Previous infection protected against asymptomatic infection [Relative Risk Ratio (RRR) of recent infection vs no infection 0.53, 95% CI 0.23-1.20] and even more against symptomatic infections [RRR 0.11, 95% CI 0.05-0.25]. Symptomatic infections increased from 70.5% in HW receiving the booster dose since < 64 days to 86.2% when time elapsed was > 130 days. CONCLUSIONS: 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.