BACKGROUND: Since the beginning of the coronavirus pandemic, various treatment options and regimens, and their combinations, have been used. However, before the start of vaccination and the introduction of biologic drugs and monoclonal antibodies, life-threatening complications occurred much more often. AIM: To assess the efficacy and safety of Tixagevimab / Cilgavimab (“Evusheld”) for the treatment of patients with comorbidities and SARS-CoV-2 infection in comparison with standard therapy protocols in vaccinated and unvaccinated people. MATERIALS AND METHODS: A retrospective study of the inpatient medical records of 290 patients with a confirmed diagnosis of moderate COVID-19 caused by SARS-CoV-2 was conducted. RESULTS: The average bed-days in the three groups varied. The lowest number was recorded in the Tixagevimab / Cilgavimab group with 9.9 days. In the vaccinated and unvaccinated groups, the corresponding values were 10.9 and 11.7 days. The duration of the COVID-19 course was minimal in the Tixagevimab / Cilgavimab with 12.6 days; in the vaccinated and unvaccinated groups, the disease lasted an average of 17.6 and 18.7 days, respectively. The percentage of lung tissue damage was the highest in the unvaccinated group with 43.2% on average, followed by the vaccinated group with 26.5% and the Tixagevimab / Cilgavimab group with 4.3%. Moreover, 53.6%, 32.5%, and 13.6% of the unvaccinated, vaccinated, and Tixagevimab / Cilgavimab groups required oxygen support, respectively. In the unvaccinated group, leukocytosis increased to 11.3×109, which was associated with the emergence of a bacterial infection and prolonged hospitalization. CONCLUSIONS: The preparation of synthetic recombinant monoclonal neutralizing antibody Tixagevimab / Cilgavimab to SARS-CoV-2 significantly reduces the severity of COVID-19 and the first day of hospitalization.