In this cohort study of patients hospitalized with non-critical COVID-19, we observed that: First, IFN-based triple therapy (IFN-β-1b plus RBV, plus LPV/r) was associated with lower 28-day mortality as compared to FPV; aHR 0.27, 95% CI (0.08–0.88). The gene discussed is IFNA1; the disease is COVID-19.