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. 2023 Sep;13(3):577-588.
doi: 10.1007/s44197-023-00139-8. Epub 2023 Jul 22.

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  1   2 , Maria Grazia Lourdes Monaco #  2 , Gianluca Spiteri #  3 , Angela Carta  1   2 , Gulser Caliskan  4 , Concepción Violán  5   6 , Pere Torán-Monserrat  5   6 , Luigi Vimercati  7 , Silvio Tafuri  7 , Paolo Boffetta  8 , Francesco Saverio Violante  8 , Emma Sala  9 , Emanuele Sansone  10 , Fabriziomaria Gobba  11 , Loretta Casolari  12 , Andreas Wieser  13   14   15   16 , Christian Janke  13 , Adonina Tardon  17 , Marta Maria Rodriguez-Suarez  18 , Filippo Liviero  19   20 , Maria Luisa Scapellato  19   20 , Marco dell'Omo  21 , Nicola Murgia  22 , Dana Mates  23 , Violeta Claudia Calota  23 , Jozef Strhársky  24 , Mariana Mrázová  25 , Enrico Pira  26 , Alessandro Godono  26 , Greta Camilla Magnano  27 , Corrado Negro  27 , Giuseppe Verlato  4 ; Orchestra WP5 Working Group
Collaborators, Affiliations

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 et al. J Epidemiol Glob Health. 2023 Sep.

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.

Keywords: Booster dose; Booster vaccination; COVID-19 breakthrough infections; COVID-19 vaccine; SARS-CoV-2; Vaccine effectiveness.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Determinants of BI after the booster dose, investigated by a two‐level logistic regression model, where level‐1 units (HW) were nested into level‐2 units (participating centres)
Fig. 2
Fig. 2
Determinants of BI investigated by a two‐level multinomial logistic regression model (outcome where 0 = no infection, 1 = asymptomatic infection, 2 = symptomatic infection), where level‐1 units (health worker) were nested into level‐2 units (participating centres)
See this image and copyright information in PMC

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