COVID-19 throughout pandemic waves and virus variants: a real-life experience in an Italian hospital.

New therapies and vaccines changed the management of COVID-19. The aim of this retrospective study was to describe characteristics, in-hospital mortality and its predictors in patients with moderate/severe COVID-19, considering the 4 different pandemic waves and viral variants' prevalence from February 2020 to January 2022. Among 1135 patients included, 873 (77%) had at least one comorbidity, 177 (16%) were immunocompromised. From waves 1 to 4, patients with severe respiratory failure and ICU admission decreased over time ( p  < 0.001), like the length of in-hospital stay ( p  < 0.001). Despite a reduction of in-hospital mortality from 19% to 11%, increased risk of death was related to older age and immunocompromising conditions, especially during the 4th wave (HR = 5.07 and HR = 10.86, p  < 0.001 respectively) while remdesivir treatment in the 3rd wave (HR = 0.41, p  = 0.010) and positive serology (aHR = 0.66, p  = 0.027) were protective for survival. These data support the need for tailoring vaccine campaign for future COVID-19 waves.