Tehran University of Medical Sciences Journal of Pharmaceutical Care 2322-4630 9 3 2021 09 28 129 136 EN Nima Rouhani Department of Infectious Diseases, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran. Elahe Karimpour-razkenari Department of Clinical Pharmacy, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Mostafa Alizadeh Forutan Department of Internal Medicine, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran. Monireh Ghazaeian Department of Infectious Diseases, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran AND Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Ebrahim Salehifar Department of Infectious Diseases, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran AND Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Sadegh Rezai Pediatric Infectious Diseases Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Sahar Fallah Department of Biostatistic, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran. 2021 05 24 2021 09 04 Backgrounds: There is no proven therapy for coronavirus disease 2019 (COVID-19) so far. The aim of this study was to evaluate the effect of interferon beta-1b combined with lopinavir/ritonavir and hydroxychloroquine in managing COVID-19.Methods: This is a non-randomized, open-label study on adult patients with moderate to severe COVID-19. The patients (≥ 18 years) received hydroxychloroquine 400 mg single dose, and lopinavir 400 mg/ritonavir 100 mg every 12 h (for 7-10 days) with or without subcutaneous interferon (IFN) beta-1b 250 mcg every other day for e primary outcome was clinical improvement in NEWS2 changes. Duration of hospital stay, mortality rate, and safety profile of therapeutic regimens were secondary outcomes.Results: Between March 20 and April 3, 2020, a total of 114 patients were recruited and 59 patients completed the study. The IFN group had a significant improvement in clinical symptoms due to a significant reduction in NEWS2 (83.3% (25) vs 48.3% (14), P= 0.004). The time to clinical response in the IFN group was shorter than the control group (7 (5-12) days vs 9.5 (7-18), P=0.037). The IFN group also showed a significantly lower rate of 28-day mortality (6.8% (2) vs 34.5% (10), P= 0.01) and a lower need for invasive ventilation (6.8% (2) vs 34.5 (10), P= 0.008). Although the duration of ICU stay was marginally shorter in the IFN group, the results were not significantly different between the two groups (P=0.06).Conclusion: IFN beta-1b could be a potential therapeutic option for patients with moderate to severe COVID-19.  https://jpc.tums.ac.ir/index.php/jpc/article/view/423