The Efficacy and Adverse Effects of Favipiravir on COVID-19 Patients: A Systematic Review and Meta-Analysis of Published Clinical Trials and Observational Studies

Background: The burden of COVID-19 on healthcare systems worldwide requires an efficient treatment option. Favipiravir, a nucleoside analog, is a potential COVID-19 treatment. Therefore, this study aimed to evaluate the efficacy and adverse events of favipiravir in COVID-19 patients.Method: In our systematic review and meta-analysis, we performed searches of PubMed, Scopus, Embase, Web of Science, the Cochrane Library, Google Scholar, European PMC, Virtual Health Library, mRCT, ClinicalTrials.gov, SIGLE, the WHO COVID-19 research article database, Covid-evidence.org, and the iSearch COVID-19 Portfolio with the latest update on February 8 th , 2021. All types of studies in which favipiravir was used on COVID-19 patients were included and extracted by two independent authors. All studies underwent systematic review, data from controlled trials underwent meta-analysis. Our protocol was registered on PROSPERO as CRD42020206305.Findings: 145 studies (15 randomized controlled trials (RCTs), one non-RCT, 21 observational studies, two case series, and 106 case reports) were included. In comparison to standard of care (SOC), favipiravir showed a higher rate of viral clearance at day 5 (RR=1·49, p=0·03), defervescence at day 3 (RR=1·91, p<0·01), chest computed tomography (CT) improvement at day 14-15 (RR=1·40, p<0·01), and hospital discharge at day 10-11 (RR=1·31, p<0·01). Regarding adverse events, the favipiravir groups had higher rates of hyperuricemia (RR=9·42, p<0·01), but lower rates of nausea (RR=0·41, p<0·01) and vomiting (RR=0·09, p=0·02).Interpretation: Adding favipiravir to the standard of care provides better outcomes for COVID-19 patients. Pregnant and lactating women as well as a history of hyperuricemia or gouty arthritis should be noticed when using favipiravir. Using favipiravir could reduce the rate of nausea and vomiting for some patients.Registration Details: Registered on PROSPERO as CRD42020206305.Funding Information: Grant Asian clinical trial network construction project (Number JP20LK0201001J0001) by Japan Agency for Medical Research and Development (AMED).Declaration of Interests: We declare no competing interests.