INTRODUCTIONCoronavirus disease (COVID-19) was first detected in Wuhan city, China in December 2019. The followed pandemic has been one of the worst threats to healthcare systems all over the world [1,2]. Healthcare workers are at a high risk of SARS-CoV-2 infection that can result in a reduced healthcare workforce [3,4]. Therefore, measuring the seroprevalence, incidence and identifying the risk factors for hospital-related SARS-CoV-2 could provide important information to control the COVID-19 within hospitals, to protect patients and healthcare workers and to save lives. Furthermore, evaluating the real-world COVID-19 vaccine performance is critical for understanding the risks and benefits of vaccination programmes. In this framework, in 2020, the European Centre for Disease Prevention and Control (ECDC) initiated two projects, coordinated by Epiconcept, France, to support the development and implementation of two multicentre European studies to: i) conduct hospital-based transmission and seroepidemiological studies, to measure seroprevalence, incidence and identifying risk factors of SARS-CoV-2 infection among healthcare workers and ii) evaluate the effectiveness of the COVID-19 vaccine in hospital-based healthcare workers. The Azienda Ospedaliero-Universitaria Policlinico “G. Rodolico - San Marco”, University of Catania, has participated in the two studies to evaluate among healthcare workers the risk factors for COVID-19 and vaccine efficacy. The aim of this work is to describe data we collected thanks to the participation in these European studies.MATERIALS AND METHODSWe conducted simultaneously the two different prospective multicentre studies in the same cohort of healthcare workers and in the same context. One study was conducted to measure risk of SARS-CoV-2 infection and identify risk factors for SARS-CoV-2 infection and seroprevalence among healthcare workers. The other one was conducted to measure product-specific COVID-19 vaccine effectiveness among hospital healthcare workers eligible for vaccination against all laboratory-confirmed SARS-CoV-2 infection. We collected information on community and in-hospitals exposures 14 days before enrolment. Once informed consent had been obtained, healthcare workers were enrolled regardless of their individual vaccination and provided a nasopharyngeal swab for RT-PCR analysis, provided a blood sample for serology testing, completed an enrolment questionnaire that includes demographic, clinical, and epidemiological information, information about vaccination history, and occupation- and community-related behaviour. The follow-up consisted in a RT-PCR test searching for SARS-CoV-2 RNA virus once a week and a blood sample for serology once a month. Participants were followed up with a weekly survey to report changes in health or vaccination status as well as likely professional and personal exposures.RESULTSDuring the study period, from July to October 2021, a total of 231 healthcare workers from the Catania site were enrolled. A decline in seroprevalence among healthcare workers was detected. During the follow-up period, 6 COVID-19 cases were detected using RT-PCR test with an incidence of 4 per 10,000 person-days. Due to the low number of infections detected during the study results on risk factors – as age, educational level and current smoking – need to be interpreted with caution. In light of the very high COVID-19 vaccine coverage rates, with nearly all healthcare workers having received at least one dose of vaccine before enrolment, comparing the incidence of SARS-CoV-2 infection or COVID-19 disease in vaccinated and unvaccinated groups is not possible because of limited sample size.CONCLUSIONSA low number of COVID-19 infections were detected during the follow-up of HCW with the information available, all of them vaccinated with two doses of RNA messenger vaccine and no previous infection. The very high COVID-19 vaccine coverage rateseriously compromises the possibility of estimating vaccine efficacy of COVID-19 vaccines by both a reduction in the power of the study and the introduction of a selection bias as unvaccinated and partially vaccinated HCW are unlikely to be representative of HCW in general. As the study on vaccine effectiveness is still on-going in many European sites, it is expected that the sample size will increase along with infections.