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Background: IFNβs are known as one of the most promising drugs used for COVID-19 treatment. This study aimed to investigate the effects of treatment with INF-β 1-a (interferon beta-1a) and IFN-β 1-b (interferon beta-1b) on COVID-19 inpatients., Methods: In this study, we retrospectively evaluated the clinical treatment outcomes of 100 patients with COVID-19 who received IFN-β 1-a and IFN-β 1-b during their hospitalization period. The rate of discharge from the hospital was considered equal to the clinical improvement and then evaluated as a primary outcome. Moreover, mortality, ICU admission and length of ICU stay, frequency of intubation and use of mechanical ventilation, duration of hospitalization, laboratory factors, and medications were assessed as secondary outcomes., Results: The median discharge time of IFN-β 1a recipients was approximately equal to that of IFN-β 1-b recipients as 9 (5-10) days and 7 (5-11) days, respectively (HR = 2.43, P = 0.75). Mortality rate was also estimated as 10% among IFN-β 1-a recipients and 14% among IFN-β 1-b recipients, which was not statistically significant (p = 0.190). ICU hospitalization rate for the IFN-β 1-a recipients and IFN-β 1-b recipients was 26% and 36%, respectively. In addition, no significant difference was found between these two intervention groups in terms of ICU length of stay (1 (0-2) vs. 1 (0-4.25(, respectively,) P = 0.357). There was no significant difference between the two study groups in terms of frequency of mechanical ventilation and length of hospital stay., Conclusion: There was no significant difference between the two groups in terms of shortening the disease time, clinical improvements and other outcomes., (Copyright © 2021. Published by Elsevier B.V.)