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Purpose: To assess the efficacy of interferon-beta1b (INF-beta1b) in combination with favipiravir in early treatment of patients with COVD-19 pneumonia. Methods: This prospective non-controlled study was performed on admitted patients with moderate to severe COVID-19 disease to Amir-Alam hospital. The diagnosis of COVID-19 pneumonia was based on positive RT-PCR test from nasopharyngeal samples and typical spiral chest CT scan findings. At the time of this study, there was the shortage of efficient anti-COVID drugs especially “Remdesivir” due to sanction of Iran. All the patients received subcutaneous IFN-beta1b plus favipiravir. The patients with severe infection received intravenous dexamethasone. Those who underwent invasive or noninvasive mechanical ventilation, at the admission onset, were excluded from the study. Results: One hundred and eighty-two patients with moderate to severe COVID-19 pneumonia were included in this study. Among182 patients, 90 cases had moderate and 92 had severe pneumonia. Twenty-one cases with severe pneumonia and 14 cases with moderate pneumonia were transferred to ICU to receive invasive or non-invasive mechanical ventilation. The mean duration of hospital ward admission and ICU stay was 10.69±7.54 and 5.45±2.72 days, respectively. One hundred and seventy-four patients (80.7 %) recovered completely and discharged without need to ICU admission. The response rate was the same in patients with moderate and severe pneumonia. Nine cases (4.9 %) were passed away. Diabetic patients had higher mortality rates. Conclusion: This study showed the efficacy of IFN-beta1b plus favipiravir in early treatment of patients with moderate to severe COVID-19 pneumonia who did not need to mechanical ventilation.