Background: Vaccination against SARS-CoV-2 (COVID-19) has become crucial for limiting disease transmission and reducing its severity, hospitalizations and mortality; however, despite universal acceptance, vaccine hesitancy is still significant. In the present manuscript, we aim to assess COVID-19-attributed mortality after the prevalence of new variants of the virus (Delta and Omicron viral strains) and to evaluate the vaccination effect. Methods: All patients that were hospitalized due to COVID-19 infection in the Respiratory Department of a tertiary referral center in central Greece between 1st of June 2021 and 1st of February 2022 were included in the present study. Results: 760 consecutive patients were included in the study; 89 (11.7%) were diagnosed with severe COVID-19 and 220 (38.7%) patients were fully vaccinated. In logistic regression, increased age (aOR = 1.12, p < 0.001), male gender (aOR = 2.29, p = 0.013) and vaccination against SARS-CoV-2 virus (aOR = 0.2, p < 0.001) were associated with mortality attributed to COVID-19 with a statistically significant association. Moreover, increased age (aOR = 1.09, p < 0.001), male gender (aOR = 1.92, p = 0.025) and vaccination against SARS-CoV-2 virus (aOR = 0.25, p < 0.001) were statistically significantly associated with clinical severity of COVID-19 infection. However, when comparing the length of hospitalization between vaccinated and unvaccinated patients, the difference was not statistically significant between the two groups (p = 0.138). Conclusions: Vaccination against SARS-CoV-2 virus had a protective effect in terms of mortality and clinical severity of COVID-19 during the fourth wave of the pandemic in Central Greece. The national vaccination policy has to focus on vulnerable populations that are expected to benefit the most from the vaccine’s protection.
