The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials

  1. Soheil Hassanipour
  2. Morteza Arab-Zozani
  3. Bahman Amani
  4. Forough Heidarzad
  5. Mohammad Fathalipour
  6. Rudolph Martinez-de-Hoyo

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Abstract

The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid/PubMed, Scopus, Web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR = 1.24, 95% CI: 1.09–1.41; P = 0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR = 1.11, 95% CI: 0.98–1.25; P = 0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR = 0.93, 95% CI: 0.67–1.28; P = 0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.

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  1. Version published to 10.1038/s41598-021-90551-6
  2. ScreenIT

    SciScore for 10.1101/2021.02.14.21251693: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationThe data extraction form includes the following items; authors name, year of the publication, study design, study sample, country of origin, mean age of participants, gender, the severity of diseases, comorbidities, type of intervention and dose, control group, follow up, randomization, blinding, allocation concealment, primary and secondary outcomes, and adverse events 3, 25.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Information sources and search strategy: Two independent reviewers (MA-Z and SH) searched electronic databases including LitCovid hub/PubMed 23, Scopus, ISI web of Sciences, Cochrane, and Scientific Information Database (SID) 24 using keywords combination (MeSH term and free term), such as “2019 nCoV” OR 2019nCoV OR “2019 novel coronavirus” OR COVID-19 OR “new coronavirus” OR “novel coronavirus” OR “SARS CoV-2” OR (Wuhan AND coronavirus) OR “SARS-CoV” OR “2019-nCoV” OR “SARS-CoV-2” and Favipiravir OR Avigan until the end of 2020.
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    We also searched two preprint databases including MedRxiv and Research Square and, the reference lists of all included studies, reviews, and clinical trial registries, for an ongoing clinical trial (see Supplementary file 1 for the final proposed PubMed search strategy).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    We assessed the risk of bias of the included studies using Cochrane Collaboration criteria, including seven items of selection bias (random sequence generation and allocation concealment), performance bias, detection bias, attrition bias, reporting bias, and other forms of bias 3, 25.
    Cochrane Collaboration
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Despite the limitation, the present study provided the information needed for treating COVID-19, suggesting that favipiravir is associated with significant clinical and laboratory improvement in most patients and it is a safe drug with no serious side effects 37. There is some evidence to support the safety and tolerability of favipiravir in short-term administration. However, more evidence is necessary to evaluate the exact long-term effects of this intervention. Due to limited evidence and other specific safety concerns, caution should be considered in the widespread use of favipiravir against the COVI D-19 epidemic 45.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.02.14.21251693v1 on medRxiv