In-hospital mortality outcomes of favipiravir in patients with moderate to severe COVID-19 infection: An emulated target trial using real-world data from the largest field hospital in Thailand

Abstract

Background Favipiravir, an antiviral agent, has been widely used to treat COVID-19 due to its potential mechanism of action, despite limited evidence of its efficacy in moderate to severe cases. Aim This study aimed to evaluate the efficacy of favipiravir in improving in-hospital mortality outcomes among patients with moderate to severe COVID-19 through an emulation of a target trial. Methods We emulated a target trial using observational data from Bussarakham field hospital, Thailand between May 14 and September 20, 2021. Patients were categorized into three groups: those receiving favipiravir with dexamethasone (FPV with Dexa), favipiravir alone (FPV), and symptomatic treatment (ST). In-hospital mortality within 30 days was the primary outcome. Results From 18,184 patients admitted to the hospital, a total of 3,193 moderate to severe COVID-19 cases were included. Of these, 2,256 (70.65%) received FPV with Dexa, 828 (25.93%) received FPV, and 109 (3.41%) received ST. The restricted mean survival times were 29.68 days (95% CI: 29.52, 29.84) for FPV with Dexa, 29.46 days (95% CI: 29.22, 29.71) for FPV, and 28.14 days (95% CI: 26.51, 29.76) for ST. Only FPV showed marginally significant difference when compared to ST. However, there was a trend in prolonging survival time in FPV with Dexa group, and the results were more pronounced in severe and hypoxic patients. Conclusion Our emulated target trial suggests favipiravir, especially with dexamethasone, offers a modest survival benefit in moderate to severe COVID-19, particularly in hypoxic patients. It supports favipiravir as a practical antiviral in settings where other antivirals are not available. Further randomized controlled studies are needed to confirm its role, alongside standard corticosteroid therapy.