Core protocol for ECDC studies of COVID-19 vaccine effectiveness against hospitalisation with severe acute respiratory infection laboratory-confirmed with SARS-CoV-2 or with seasonal influenza : version 4.0

This core protocol for ECDC studies of VE against hospitalisation with severe acute respiratory infection (SARI) laboratory-confirmed with SARS-CoV-2 or with influenza, version 4.0, represents an update to the main elements for a multi-country hospital-based study of COVID-19 vaccine effectiveness in patients hospitalised with SARI, initially published as version 1.0, with the latest update being version 3.0. This version includes updates on methodology for CVE pooled analyses and inclusion on new variables for data collection, including on Respiratory Syncytial Virus (RSV) testing and vaccination status. The larger sample size achieved by combining data from multiple sites will provide more statistical power to meet more specific objectives. The protocol can be implemented for COVID-19 and/or influenza. A specific feasibility study to assess effectiveness of RSV immunisation products is being published separately. The proposed method is a case-control study using a test-negative design. The study population consists of individuals of all ages, belonging to the target group for COVID-19 or influenza vaccination, hospitalised with SARI symptoms and no contra-indication for being vaccinated with the vaccine of interest. It would be beneficial if countries also test for other respiratory viruses (as appropriate depending on time of year). This core protocol is primarily intended to guide the implementation of ECDC-funded studies. However, ECDC encourages that vaccine effectiveness studies are conducted, using this protocol as a basis, in countries not currently planning to participate in ECDC-funded studies. The use of consistent protocols will facilitate the comparability of study results across studies, countries and study sites.