Combination of (interferon beta-1b, lopinavir/ ritonavir and ribavirin) versus favipiravir in hospitalized patients with non-critical COVID-19: A cohort study

Abstract

Objectives Our study aims at comparing the efficacy and safety of IFN-based therapy (lopinavir/ritonavir, ribavirin, and interferon β-1b) vs. favipiravir (FPV) in a cohort of hospitalized patients with non-critical COVID-19. Methods Single center observational study comparing IFN-based therapy (interferon β-1b, ribavirin, and lopinavir/ritonavir) vs. FPV in non-critical hospitalized COVID-19 patients. Allocation to either treatment group was non-random but based on changes to national treatment protocols rather than physicians’ selection (quasi-experimental). We examined the association between IFN-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate. Results The study cohort included 222 patients, of whom 68 (28%) received IFN-based therapy. Antiviral therapy was started at a median of 5 days (3–6 days) from symptoms onset in the IFN group vs. 6 days (4–7 days) for the FPV group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FPV (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.27 (0.08–0.88)). No difference in hospitalization duration between the 2 groups, 9 (7–14) days vs. 9 (7–13) days, P = 0.732 was found. IFN treated group required less use of systemic corticosteroids (57%) as compared to FPV (77%), P = 0.005 after adjusting for disease severity and other confounders. Patients in the IFN treated group were more likely to have nausea and diarrhea as compared to FPV group (13%) vs. (3%), P = 0.013 and (18%) vs. (3%), P<0.0001, respectively. Conclusion Early IFN-based triple therapy was associated with lower 28-days mortality as compared to FPV.