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In this work we present an updated version of "Safe University", a protocol aimed to ensure the safe operation of academic institutions during the SARS-CoV-2 pandemic. The protocol is detailed, addressing all aspects of the actions that are required, ranging from controlled access to the university premises and tracking of immunity status to air quality provisions and organization of classes and teaching methods and more. A step-by-step guide and a sample timeline are included, to facilitate practical implementation. The protocol was first developed in the summer of 2021, when the Delta variant had first emerged but not yet dominated, with the aim to support the operation of Greek universities at the beginning of the 2021–2022 academic year. Since then, it has been updated to reflect the evolution of the virus and the pandemic, as well as the developments in the relevant scientific knowledge and additional monitoring, safeguarding and treatment tools that humanity now possesses. It has also been given a more generic form, making it suitable and adjustable for other countries and cultural/political environments as well as other respiratory viruses. With some additional adjustments, it can also be suitable to deal with epidemics from non-respiratory viruses that may arise in the future. [ABSTRACT FROM AUTHOR]