Effectiveness of favipiravir in COVID-19: a live systematic review

Abstract

We performed a systematic review and meta-analysis for the effectiveness of Favipiravir on the fatality and the requirement of mechanical ventilation for the treatment of moderate to severe COVID-19 patients. We searched available literature and reported it by using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Until June 1, 2021, we searched PubMed, bioRxiv, medRxiv, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar by using the keywords “Favipiravir” and terms synonymous with COVID-19. Studies for Favipiravir treatment compared to standard of care among moderate and severe COVID-19 patients were included. Risk of bias assessment was performed using Revised Cochrane risk of bias tool for randomized trials (RoB 2) and ROBINS-I assessment tool for non-randomized studies. We defined the outcome measures as fatality and requirement for mechanical ventilation. A total of 2702 studies were identified and 12 clinical trials with 1636 patients were analyzed. Nine out of 12 studies were randomized controlled trials. Among the randomized studies, one study has low risk of bias, six studies have moderate risk of bias, and 2 studies have high risk of bias. Observational studies were identified as having moderate risk of bias and non-randomized study was found to have serious risk of bias. Our meta-analysis did not reveal any significant difference between the intervention and the comparator on fatality rate (OR 1.11, 95% CI 0.64–1.94) and mechanical ventilation requirement (OR 0.50, 95% CI 0.13–1.95). There is no significant difference in fatality rate and mechanical ventilation requirement between Favipiravir treatment and the standard of care in moderate and severe COVID-19 patients.

Effectiveness of Remdesivir, Lopinavir/Ritonavir, and Favipiravir for COVID-19 Treatment: A Systematic Review

“…There is no evidence that favipiravir reduces mortality or the use of mechanical ventilation among moderate and severe COVID-19 patients. 46 Previous in silico study suggested, F-RTP, which is the active form of favipiravir binds to the RdRp active site of SARS-CoV-2, SARS-CoV, and MERS-CoV in the presence of agents and proteins. 47 Favipiravir is a purine nucleic acid analog licensed for the treatment of influenza since it efficiently inhibits influenza, norovirus, and Ebola viruses’ RNA-dependent RNA Polymerase (RdRp).…”

Favipiravir Effectiveness and Safety in Hospitalized Moderate-Severe COVID-19 Patients: Observational Prospective Multicenter Investigation in Saudi Arabia

“…In general, favipiravir has shown a consistent safety profile with no significant adverse events compared to the no favipiravir group in the recommended dose range (6,11,14). While in terms of efficacy in moderate and severe COVID-19 conflicting results were reported (9)(10)(11). The initial endorsement of favipiravir was based on its effect to reduce viral clearance (14,15), however later in the pandemic, viral clearance was shown not to be the proper measure of medication effectiveness, with many patients continuing to have positive RT-PCR results even after complete recovery (9,16).…”

“…It has been given restricted authorization in several countries, including India and Russia, while it is under investigation in the USA, Japan and elsewhere (5). Although favipiravir is an oral medication that has shown positive clinical effects in milder cases of COVID-19 disease (6), its clinical effect in more advanced moderate and severe COVID-19 has been inconsistent and need more investigation (7)(8)(9).…”

“…A recent meta-analysis showed no significant difference in fatality rate and mechanical ventilation requirement between favipiravir treatment and the standard of care in 1,636 moderate and severe COVID-19 patients (9). In comparison, a retrospective observational study of 480 moderate to critical patients associated the favipiravir use with accelerated discharge rate and less progression to mechanical ventilation (10).…”

Unraveling the Enzymatic Mechanism of the SARS-CoV-2 RNA-Dependent-RNA-Polymerase. An Unusual Active Site Leading to High Replication Rates

“…As a matter of fact, some nucleotide analogous, 29,30 also used against some retroviruses such as Human Immunodeficiency Virus (HIV), have been proposed for SARS-CoV-2 treatment and while they have shown interesting in vitro and in vivo efficiency their clinical use is strongly limited also by rather sever side-effects and a non-trivial pharmacokinetic and administration. Between the proposed nucleotide analogous inhibiting SARS-CoV-2, we may cite Remdesivir, 31 acting by impeding the RNA translocation, 32 which follows the inclusion of a new nucleotide to free the active site and slide along the template, and Favipiravir, 33,34 which instead directly inhibits the RNAP catalytic site. 35 While the structure of SARS-CoV-2 RNAP has been resolved, 24,35 also in presence of inhibitors, the studies focusing on the enzymatic mechanism from a molecular and biochemical point of view are rare.…”