The end of 2019 saw the emergence of a novel severe acute respiratory syndrome: coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). As of December 2023, eight vaccines (Comirnaty, Spikevax, Vaxzevria, Jcovden Valneva, Nuvaxovid, VidPrevtyn, and Bimervax) have been authorised for use in the European Union (EU) by the European Commission, based on the scientific opinion of the European Medicines Agency (EMA). Updated formulations of Comirnaty and Spikevax to protect against the original and BA.4-5 strains were authorised in 2022. Adapted versions using the Omicron XBB.1.5 strain were authorised on 31 August (Comirnaty), 15 September (Spikevax), and 31 October (Nuvaxovid) 2023 [1]. In 2020, the European Commission emphasised the importance of continuously monitoring the safety and effectiveness of vaccines in the EU/EEA and called on ECDC and EMA to develop a structured post-authorisation monitoring platform for vaccines, prioritising COVID-19 vaccines. In November 2020, the European Commission proposed to the European Parliament and the Council of the EU a change to the mandates of EMA and ECDC in the context of its COVID-19 lessons learned package and the creation of a European Health Union, empowering the two agencies to jointly coordinate independent vaccine monitoring studies. As a result, at the end of 2020, utilising the lessons learned from other vaccine effectiveness studies, ECDC started building infrastructure to perform COVID-19 vaccine effectiveness studies. The infrastructure aims to build a system to regularly monitor vaccine effectiveness and perform studies in different settings, and depending on the setting, to provide information on different outcomes (severe disease, moderate disease, infection, transmission, etc). The studies have been embedded in a project called VEBIS (Vaccine Effectiveness, Burden and Impact Studies). This generic protocol describes the design and methods for a prospective multi-country cohort study of hospitalbased healthcare workers (HCWs) to evaluate the effectiveness of COVID-19 vaccines in preventing laboratoryconfirmed SARS-CoV-2 infection. The combination of data from multiple sites aims at providing sufficient statistical power to meet both the overarching primary objective and a range of more specific secondary objectives. This protocol has been adapted to the rapid vaccine roll-out for COVID-19 in many countries and accommodates the establishment of HCW cohorts subsequent to the implementation of vaccination programmes.
