The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies

Hung, Dang The; Ghula, Suhaib; Aziz, Jeza Muhamad Abdul; Makram, Abdelrahman M; Tawfik, Gehad Mohamed; Abozaid, Ali Ahmed-Fouad; Pancharatnam, Rohan Andrew; Ibrahim, Amr Mohamed; Shabouk, Muhammad Besher; Turnage, Morgan; Nakhare, Saloni; Karmally, Zahra; Kouz, Basel; Le, Thuy; Alhijazeen, Suleiman; Phuong, Nguyen Quoc; Ads, Alaa Mohamed; Abdelaal, Ali Hussein; Nam, Nguyen Hai; Iiyama, Tatsuo; Kita, Koichi; Hirayama, Kenji; Huy, Nguyen Tien

doi:10.1016/j.ijid.2022.04.035

Cited by 34 publications

(35 citation statements)

References 84 publications

(76 reference statements)

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“…The study reported a comparable onset of SARS-CoV-2 PCR negativity in the favipiravir group compared with the hydroxychloroquine group (8.3 days vs. 8.1 days; p = 0.79) [ 13 ]. A recent meta-analysis of 17 clinical trials of favipiravir reported the significant benefit of favipiravir on clinical and virological outcomes among hospitalized patients [ 20 ]. Additionally, there was no statistically significant difference in the mortality rate between the favipiravir group and the control group [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…A recent meta-analysis of 17 clinical trials of favipiravir reported the significant benefit of favipiravir on clinical and virological outcomes among hospitalized patients [ 20 ]. Additionally, there was no statistically significant difference in the mortality rate between the favipiravir group and the control group [ 20 ]. Favipiravir seems to be more beneficial among patients with mild-to-moderate COVID-19 and patients who received early favipiravir therapy [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, there was no statistically significant difference in the mortality rate between the favipiravir group and the control group [ 20 ]. Favipiravir seems to be more beneficial among patients with mild-to-moderate COVID-19 and patients who received early favipiravir therapy [ 20 ]. The benefits of early favipiravir initiation in mild COVID-19 cases are in need of further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand

Rattanaumpawan

Jirajariyavej²,

Lerdlamyong

et al. 2022

Antibiotics

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Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the real-world effectiveness and optimal dosage of favipiravir for treating COVID-19 are limited. We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data. Among 247 COVID-19 patients, 63 (23.0%) received ≥1 dose of favipiravir. Of these 63 patients, 61.9% were male with a median age of 48 years (range 22–85 years), 27.0% required an O2 nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2 therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5 (0–16). The Day-7 clinical improvement rate [95%CI] was 66.7% [53.7–78.0%] in all patients, 92.5% [75.7–99.1%] in patients who did not require O2 supplementation, and 47.2% [0.4–64.5%] in patients who required O2 supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%. A multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement (odds ratio (95%CI); p-value): older age (0.94 (0.89–0.99); p = 0.04), a higher baseline NEWS2 score (0.64 (0.47–0.88); p = 0.006), and a lower favipiravir loading dose (≤45 mg/kg/day) (0.04 (0.005–0.4); p = 0.006). In conclusion, our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand

Rattanaumpawan

Jirajariyavej²,

Lerdlamyong

et al. 2022

Antibiotics

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“…The suggested modes of action of favipiravir comprises a mix of both chain termination and mutator events ( 18 ). Several adverse events have been reported during use of molnupiravir and favipiravir, including diarrhea, dizziness, and nausea for molnupiravir ( 19 ), and hyperuricemia and increased alanine aminotransferase for favipiravir ( 20 ). Importantly, unlike remdesivir, cardiovascular side effects have not been reported with the use of molnupiravir or favipiravir.…”

Section: Introductionmentioning

confidence: 99%

Activation of the urotensin-II receptor by anti-COVID-19 drug remdesivir induces cardiomyocyte dysfunction

Ogawa

Ohira

Ikuta

et al. 2022

Preprint

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Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular (CV) side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor (GPCR) screening in combination with structural modeling and found that remdesivir is a selective agonist for urotensin-II receptor (UTS2R). Functionally, remdesivir treatment induced prolonged field potential in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and reduced contractility in neonatal rat cardiomyocytes, both of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively attenuated by antagonizing UTS2R signaling. Finally, we characterized the effect of 110 single-nucleotide variants (SNVs) in UTS2R gene reported in genome database and found four missense variants that show gain-of-function effects in the receptor sensitivity to remdesivir. Collectively, our study illuminates a previously unknown mechanism underlying remdesivir-related CV events and that genetic variations of UTS2R gene can be a potential risk factor for CV events during remdesivir treatment, which collectively paves the way for a therapeutic opportunity to prevent such events in the future.

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“…A meta-analysis was conducted for randomized controlled trials (RCTs) and non-RCTs [ 63 ]. Overall, 157 studies (24 RCTs, 1 non-RCT, 21 observational studies, 2 case series, and 106 case reports) were included.…”

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confidence: 99%

Perspective: repurposed Drugs for COVID-19

2022

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IntroductionThe article aims to emphasize the necessity of proper research design, both scientifically and ethically, in order to provide good evidence for physicians to base their decisions on when prescribing drug treatment.Material and methodsResearch articles and guidelines related to therapy of COVID-19 were searched from the PubMed database.ResultsOnly remdesivir and tocilizumab are medicines that have been approved by the US FDA’s decision to approve their clinical use in moderate and severe COVID-19.ConclusionsFavipiravir, ivermectin and andrographolide need further well-conducted research to confirm the efficacy and safety against COVID-19 at different stages.

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The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies

Cited by 34 publications

References 84 publications

Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand

Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand

Activation of the urotensin-II receptor by anti-COVID-19 drug remdesivir induces cardiomyocyte dysfunction

Perspective: repurposed Drugs for COVID-19

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