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.

Fig 1. Distribution of treatment modalities over time.

Fig 2. Kaplan–Meier curves for survival at 28 days follow up.

Cox proportional model has been adjusted for both patient baseline variables at admission (patients’ age, male sex, body mass index, SpO2) and patient COVID-19 related severity variables during hospital stay (serum CRP, ferritin, and D-Dimer, and bilirubin levels, WBC, oxygen needs and systemic use of dexamethasone).

Fig 3. Comparison of proportions of patients requiring corticosteroids or tocilizumab during their treatment course in the interferon-based triple therapy vs. favipiravir groups*.

*The use of supportive treatments such as tocilizumab and systemic corticosteroids between IFN-based therapy vs. FPV therapy groups was evaluated by logistic regression models adjusted for both patient baseline variables at admission (patients’ age, male sex, body mass index, SpO2) and patient COVID-19 related severity variables during hospital stay (serum CRP, ferritin, and D-Dimer, and bilirubin levels, WBC, and oxygen needs).