Favipiravir Efficacy and Safety for the Treatment of Severe Coronavirus 2019. A Retrospective Study.

Abstract

Background: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. Methods: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. Results: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01–1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. Conclusion: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial

“…Favipiravir has been recommended and was widely used as a treatment for COVID-19 in some countries, including Thailand ( https://ddc.moph.go.th/viralpneumonia/eng/file/guidelines/g_treatment.pdf ). Although some observational studies have suggested benefit from favipiravir [ 10 – 14 ], and a large clinical benefit was reported in one open-label randomised controlled trial (with shortening of time to clinical improvement from 14 to 2 days in hospitalised patients) [ 15 ], the other reported randomised trials have either shown no benefit, or the evidence of clinical efficacy has been marginal or unconvincing [ 16 – 29 ]. However, several of these studies were conducted in hospitalised patients, in whom the window of opportunity for antivirals to benefit may have closed.…”

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open- label, randomised, controlled adaptive platform trial

“…Favipiravir has been recommended, and was widely used as a treatment for COVID-19 in some countries, including Thailand (10). Although some observational studies have suggested bene t from favipiravir (11)(12)(13)(14)(15), and a large clinical bene t was reported in one open-label randomised controlled trial (shortening of time to clinical improvement from 14 to 2 days in hospitalised patients) (16), the other reported randomised trials have either shown no bene t, or the evidence of clinical e cacy has been marginal or unconvincing (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). However, several of these studies were conducted in hospitalised patients in whom the window of opportunity for antivirals to bene t may have closed.…”