Favipiravir Treatment Research Articles

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals

PurposeWe aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. MethodsWe used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. ResultsIn the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. ConclusionFrom the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

Follow-up of Favipiravir-Induced Nail Fluorescence: Implications for Nail and Drugs.

Favipiravir creates fluorescence on nails, which can be seen with Wood's light. The objectives of this study are to examine the properties of fluorescence in the nail due to favipiravir and to observe whether other drugs also produce fluorescence in the nail. The research is descriptive, prospective, and quantitative. This study recruited 30 healthcare workers who received favipiravir treatment and 30 volunteers who took or did not take any medication except favipiravir from March 2021 to December 2021. Fingernails of the patients and control groups were examined under Wood's light in the darkroom. If fluorescence was observed in the fingernails, we followed up once a month until the fluorescence disappeared. We calculated the nail growth rate by dividing the distance of nail fluorescence from the proximal nail fold by the number of days since favipiravir was started. We found nail fluorescence in all patients receiving a loading dose of favipiravir. The fluorescence in the nail decreased and disappeared in the 3rd month. The average nail growth rate at the first visit was 0.14 mm/day. The nail growth rate at the second visit was 0.10 mm/day. A statistically significant difference was found between the first and second visit nail growth rates (z: -2.576; p=0.010<0.05). We found that other drugs did not produce any fluorescence in the nail. Nail fluorescence induced by favipiravir is dose-dependent and decreases in intensity over time. Nail fluorescence due to favipiravir is likely due to the active ingredient of the drug.

Comparison of Monoclonal Antibody Cocktail (Casirivimab-Imdevimab) Treatment With Remdesivir and Favipiravir in Mild to Moderate COVID-19 Infection: A Retrospective Study

Introduction: Favipiravir and remdesivir are antiviral drugs being used in the present pandemic and were also used previously for other viral infections in the past. Monoclonal antibody (Mab) Casirivimab-Imdevimab is a Coronavirus Disease 2019 neutralising antibody approved in the last one year. Therefore, a clinical comparison with the existing treatment modalities is imperative. Aim: To compare Mab with remdesivir and favipiravir for mild to moderate COVID-19 disease. Materials and Methods: A retrospective, observational and single-centre study was conducted at a COVID-19 infection facility and private tertiary care hospital, Mumbai, Maharashtra, India. Data of patients admitted during the period of 1st June 2021 to 31st August 2021 was collected and analysed in the months of September 2021 and October 2021. Adults participants diagnosed to have COVID-19 infection, not requiring critical care or oxygen therapy were included in the study. Time to recovery from treatment onset and the need for treatment escalation were the primary outcome measures. Data was entered into Microsoft Excel spreadsheet version 16 and analysed. Statistical analysis was carried out using Chi-square test for the significance of association between tabulated values of data for qualitative and categorical data. Two-tailed unpaired t-test and Analysis of Variance (ANOVA) was used for quantitative tabulated data. Results: This study included 158 participants, grouped into remdesivir (n=63), favipiravir (n=30) and Mab (n=65) treatment groups. Gender distribution was comparable in all groups (p-value=0.08). The three groups were compared for need of treatment escalation and time of recovery. The Mab treatment group (on comparing with other treatment arms) had earlier symptom recovery when given to patients with mild COVID-19 disease (p-value=0.006 for major symptoms) or when treatment was started within five days of symptom onset (p-value &lt;0.001). Patients in Mab treatment group with mild illness required no treatment escalation compared to other groups (p-value=0.011). However, time to recovery patients in all treatment groups was comparable in case of patients with moderate COVID-19 illness (p-value=0.7381). In patients with moderate COVID-19 illness Mab treatment group required more frequent treatment escalation compared to remdesivir treatment group (p-value=0.044), when treatment was started within 5 days of symptom onset remdesivir and mab were comparable for treatment escalation (p=0.144). Vaccination status of the three groups differed significantly (p-value=0.033) hence a further subanalysis was done. On further analysis, non-vaccinated patients receiving Mab recovered from minor symptoms (p-value=0.0006) earlier than those receiving Remdesivir. Amongst the participants of the Mab treatment-group, vaccinated and non-vaccinated patients had comparable recovery time and need for treatment escalation (p-value=0.57 and p-value=0.76, respectively). Participants who received Mab-treatment within five days of symptom onset; recovered earlier compared to those who received Mab treatment after five days (p-value=0.019). Conclusion: Monoclonal antibody treatment group compared to the other treatment groups had earlier recovery in non vaccinated patients, mild COVID-19 disease, and when treatment was started before or on the 5th day of symptom onset.

Evaluation of PCR Negativity in Respiratory Specimens of COVID-19 Patients After Hydroxychloroquine and/or Favipiravir Treatment

Objective: We evaluated PCR negativity in oropharyngeal and nasopharyngeal secretions of COVID-19 patients at the end of hydroxychloroquine and/or favipiravir treatments. Methods: Study inclusion criteria were being hospitalized, being older than 18 years, PCR positivity in oropharyngeal and nasopharyngeal secretions and being tested for SARS CoV-2-RNA PCR after treatment. Initially hydroxychloroquine treatment (group 1) was administered to the patients according to COVID-19 guide of Health Ministry. Favipiravir (group 2) alone or in combination with hydroxychloroquine (group 3) was administered to patients who were unresponsive to hydroxychloroquine or had severe pneumonia or were admitted to intensive care unit. Control respiratory specimens were taken no earlier than 24 hours, after the end of therapy. Repeated tests with 24–48-hour intervals were performed in patients with still positive PCR test results. The detection of SARS CoV-2-RNA was made by real-time PCR. Results: The study group included 492 patients who received treatment. Mean duration of symptoms was similar among three groups. PCR negativity rate was 52.8% in the specimens taken 24 hours after the end of treatment. PCR negativity rates was 27.9% (200/492) in 48 hours after the end of treatment, %13.8 (123/492) in 72nd hour and %3.8 (80/492) in 96th hour. The ratios of PCR negativity for all specimen days were similar in three groups. There was no statistically significant difference between the groups for time to PCR negativity from the date of positivity and after the end of treatment. We determined that early or late treatment did not make a difference in terms PCR negativity time. Conclusion: No difference was found in terms of the ratios of PCR negativity or time for negativity in oropharyngeal and/or nasopharyngeal specimens taken after the end of treatment in COVID-19 patients receiving hydroxychloroquine and/or favipiravir treatment.

Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients.

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort's characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ± 14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141-2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.

The effect of high-dose vitamin C on renal functions in COVID–19 patients

Background: With its important properties, Vitamin C has been used in several diseases and sepsis. COVID-19 may cause sepsis, and therefore high dose Vitamin C has been integrated to the treatment protocols.Concerning the potential risk of oxalate nephropaty related with the use of long term or high dose Vitamin C, we retrospectively evaluated the COVID-19 patients treated with the high dose intravenous Vitamin C, in terms of kidney dysfunction. Material and Method: Critically ill COVID-19 patients who were given Vitamin C 45-50 gr/day/5 days (Group C, n=21), and the ones who did not (Group NC, n=22) along with the hydroxychloroquine- favipiravir treatment were compared in terms of developing renal dysfunction within the 15 days of ICU stay. Results: There were no difference in the development of renal dysfunction between the groups with and without Vitamin C treatment (p&gt;0.05). But when the patients who had KDIGO stage 1 kidney damage on admission, and had worsening renal dysfunction during ICU stay were excluded, patients groups were more similar and the development of the renal failure was significantly more in Vitamin C group(p&lt;0.05). Conclusion: We conclude that when administering high dose parenteral Vitamin C, kidney functions should be carefully assessed.

An Unusual Presentation of a Patient with Covid-19 Infection—Lemierre’s Syndrome

Lemierre’s syndrome refers to septic thrombophlebitis of the internal jugular vein that is rarely seen after an oropharyngeal infection. We present the case of a 64-year-old female patient with Covid-19 infection and Lemierre’s syndrome. Contrast-enhanced computed tomography of the neck revealed thrombosis in the left internal jugular vein and non-contrast-enhanced computed tomography of the thorax was consistent with Covid19 infection. The patient was immediately hospitalized. Systemic antibiotics, anticoagulation therapy, and favipiravir treatment for Covid-19 infection were started. Unfortunately, the patient died about two weeks after hospitalization. To the best of our knowledge, this is the first case of Lemierre’s syndrome and Covid-19 overlap. Clinical suspicion of Lemierre’s syndrome is important for rapid diagnosis. During this Covid-19 pandemic, we should keep in mind that any patient may have Covid-19 infection. In addition to the patient’s primary disease, with clinical or laboratory suspicion of Covid-19 infection, diagnostic tests for it should also be conducted.

Early diagnosis by antigen test kit and early treatment by antiviral therapy: An ambulatory management strategy during COVID-19 crisis in Thailand.

This study aimed to assess the clinical characteristics of patients who registered at the Siriraj Favipiravir Clinic and to share our experiences in this comparatively unique clinical setting.This retrospective study included patients who registered at the Siriraj Favipiravir Clinic during August 11, 2021 to September 14, 2021. Included adult patients were those with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection confirmed by antigen test kit (ATK) or real-time reverse transcription-polymerase chain reaction, no favipiravir contraindication, no prior COVID-19 treatment, and not receiving care from another medical facility. Demographic data and outcomes were collected and analyzed.Of the 1168 patients (mean age: 44.8 ± 16.4 years, 55.7% female) who registered at the clinic, 117 (10%) did not meet the treatment criteria, and 141 (12%) patients did not pick up their medication. One-third of patients had at least 1 symptom that indicated severe disease. Higher proportion of unvaccinated status (56.7% vs 47.5%, P = .005), higher proportion of persons with risk factors for disease progression (37.7% vs 31.3%, P = .028), and longer duration between the date of clinic registration and the date of positive diagnostic test (3 vs 2 days, P = .004) were significantly more commonly observed in the severe disease group compared to the nonsevere disease group. The duration between symptom onset and the date of clinic registration was significantly longer in the real-time reverse transcription-polymerase chain reaction group than in the ATK group (6 vs 4 days, P < .001). Most patients (90.0%) had completed favipiravir treatment regimen. The improvement and mortality rates were 86.7% and 1.2%, respectively.COVID-19 severity is associated with vaccination status, baseline risk factors, and timing between disease detection and treatment. The use of ATK influences patients to seek treatment significantly earlier in ambulatory setting. Our early diagnosis and antiviral treatment strategy yielded favorable results in an outpatient setting during a COVID-19 outbreak in Thailand.

EE43 Budget Impact Analysis of Favipiravir (AVIGAN®) for the Treatment of Patients with Confirmed Infection with SARS-COV2 in Mexico

The novel coronavirus (SARS-CoV-2) outbreak began in late December 2019, declared a pandemic on March 11, 2020, rapidly spread worldwide, critically impacting public health. As new treatments become available, healthcare professionals worldwide develop treatment algorithms to maximize patient benefit and minimize the impact on healthcare resources. Due to the urgency of the situation, a number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. This study aims to evaluate the Budget Impact of favipiravir plus supportive treatment (ST) compared to only ST in Mexico to treat COVID-19 mild to moderate patients.

Adverse effects associated with favipiravir in patients with COVID-19 pneumonia: a retrospective study.

Favipiravir is generally used in treating coronavirus disease 2019 (COVID-19) pneumonia in Turkey. To determine the side effects of favipiravir and whether it is a good treatment option. Retrospective study conducted in Atatürk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara, Turkey. 357 patients who completed favipiravir treatment at the recommended dose were included. 37 patients with drug side effects and 320 patients without drug side effects were examined in two groups. Side effects were observed in 37 (10.36%) out of 357 patients using favipiravir. The most common side effect was liver dysfunction, in 26 (7.28%) of the patients. The following other side effects were also observed: diarrhea (1.4%), nausea (0.84%), abdominal pain (0.28%) and thrombocytopenia (0.28%). One patient (0.28%) presented both increased transaminases and nausea. In this study, it was determined that favipiravir may constitute an alternative for treating COVID-19 pneumonia given that its side effects are generally well tolerated and not serious.

The efficacy of favipiravir treatment in hemodialysis patients with COVID 19

Corona Virus 2 (SARS-CoV 2), a recent coronavirus was first discovered in Wuhan, China in December 2019 [1]. Previous coronavirus infections, namely Middle-East Respiratory Syndrome (MERS-CoV ) and SARS-CoV have been reported to damage the respiratory system and cause serious outbreaks [2]. Major complaints are shortness of breath, cough, fever, and diarrhea [3,4]. Lung involvement is the most common form of infection, and is characterized by bilateral lung infiltrates [5,6]. The infection leads to cytokine storm and organ dysfunction and may consequently death. The diagnosis is suspected in presence of contact history, respiratory symptoms, fever, chest radiology, and biochemical parameters. The diagnosis is confirmed with Reverse Transcription-Polymerase Chain Reaction (RT PCR) positivity for COVID-19 in the nasopharyngeal swab [7]. It has been reported that elderly patients are more prone to severe coronavirus disease, just as in hemodialysis patients with additional comorbidities [5]. Since the immune system is low in Chronic Kidney Disease (CKD) patients, their tendency to infections is increased [8,9]. Good supportive treatment and infection treatment should be done [10]. CKD is also associated with an increased risk for pneumonia. Mortality rates related to lung infection in CKD seem to be 15-16 times higher than in the general population [9,11]. The use of several antiviral drugs, such as chloroquine phosphate, lopinavir/ritonavir, interferonalpha, ribavirin has been studied, and some clinical trials focusing on virus RNA dependent RNA Polymerase (RdRp) inhibitors have been initiated. Favipiravir, a purine-nucleic acid analog and RdRp inhibitor which has been approved for use in influenza, is also considered in clinical trials [12,13]. The data on dialysis-dependent patients with COVID-19 are limited, and recommendations are based on expert opinion and case series. There are no studies about the use of favipiravir in patients with renal failure in the literature. In this study, we aimed to describe our experience of favipiravir treatment in dialysis-dependent patients.

Newly developed artificial intelligence algorithm for COVID-19 pneumonia: utility of quantitative CT texture analysis for prediction of favipiravir treatment effect

PurposeUsing CT findings from a prospective, randomized, open-label multicenter trial of favipiravir treatment of COVID-19 patients, the purpose of this study was to compare the utility of machine learning (ML)-based algorithm with that of CT-determined disease severity score and time from disease onset to CT (i.e., time until CT) in this setting.Materials and methodsFrom March to May 2020, 32 COVID-19 patients underwent initial chest CT before enrollment were evaluated in this study. Eighteen patients were randomized to start favipiravir on day 1 (early treatment group), and 14 patients on day 6 of study participation (late treatment group). In this study, percentages of ground-glass opacity (GGO), reticulation, consolidation, emphysema, honeycomb, and nodular lesion volumes were calculated as quantitative indexes by means of the software, while CT-determined disease severity was also visually scored. Next, univariate and stepwise regression analyses were performed to determine relationships between quantitative indexes and time until CT. Moreover, patient outcomes determined as viral clearance in the first 6 days and duration of fever were compared for those who started therapy within 4, 5, or 6 days as time until CT and those who started later by means of the Kaplan–Meier method followed by Wilcoxon’s signed-rank test.Results% GGO and % consolidation showed significant correlations with time until CT (p < 0.05), and stepwise regression analyses identified both indexes as significant descriptors for time until CT (p < 0.05). When divided all patients between time until CT of 4 days and that of more than 4 days, accuracy of the combined quantitative method (87.5%) was significantly higher than that of the CT disease severity score (62.5%, p = 0.008).ConclusionML-based CT texture analysis is equally or more useful for predicting time until CT for favipiravir treatment on COVID-19 patients than CT disease severity score.

Favipiravir for the treatment of COVID-19 pneumonia: Can we predict the response to treatment?

Early experience with favipiravir in the treatment of COVID-19 is promising, but no clinical data have been published in medical journals. This study aimed to review the experience with favipiravir treatment for COVID-19 pneumonia and to examine whether there are any predictors of treatment response. Fifty-six patients with severe or progressive pneumonia associated with COVID-19 who were treated with favipiravir monotherapy for at least five days were included in this retrospective study. Treatment response was defined as clinical recovery without any need for admission into the intensive care unit and/or anti-cytokine therapy. The demographic, clinical, laboratory and radiographic features of the patients were compared between favipiravir-responders and non-responders. Of the 56 patients, 34 patients (60.7%) responded to treatment and recovered. There was no difference in the demographic, clinical, and radiographic findings between the responders and non-responders. The inflammatory biomarkers were also similar except for the CRP levels on the day favipiravir was started [74 (36-111) vs. 118.5 (46.5-203) mg/L, respectively, p = 0.043]. There was also a significant difference in the median time to defervescence [1 (1-2) vs. 3.5 (1.75-9.25) days, respectively]. Of clinical interest, 27 (79.4%) and 31 (91.2%) of the responders became afebrile within two and four days, respectively. The response rate was lower in patients who presented severe pneumonia associated with respiratory failure. Patients with non-severe pneumonia at admission and whose fever resolved within two days of treatment are more likely to improve with favipiravir.

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

ObjectivesThere are limited data on the efficacy and safety of favipiravir antiviral in coronavirus disease 2019 (COVID-19), particularly in the more progressed disease phase. This study aims to evaluate the favipiravir effect on reducing the length of hospital stay and in-hospital mortality among moderate and severe hospitalized COVID-19 patients.MethodsA prospective, multicenter observational study was conducted that included moderate and severe hospitalized adult COVID-19 patients in four major regions (Riyadh (Riyadh), Eastern (Dammam), Al-Qassem (Buraydah), and Macca (Jeddah) of Saudi Arabia. For the primary outcome of all-cause mortality, a Cox proportional hazard analysis was performed. While the association between favipiravir use and length of hospital stay was determined using adjusted generalized linear model. This study was approved by the Central Institutional Review Board in The Saudi Ministry of Health (MoH) with the approval number IRB # 20-85-M.ResultsThis study included 598 moderate and severe COVID-19 patients, of whom 156 (26%) received favipiravir. Favipiravir treatment was associated with more extended hospital stays (14 vs. 10 median days, P = 0.034) and higher mortality rate (aHR 3.63; 95% CI 1.06–12.45) compared to no favipiravir regimen. Despite lack of effectiveness, favipiravir use was only associated with higher diarrhea adverse effects (12 vs. 5%, P = 0.002), but it did not affect the renal and liver profiles of patients.ConclusionFavipiravir was ineffective in reducing the length of hospital stay and in-hospital mortality in patients with moderate and severe COVID-19.

Efficacy of Favipiravir in treatment of mild & moderate COVID-19 infection in Nepal: a multi-center, randomized, open-labelled, phase III clinical trial

PurposeTo study tolerability and outcome of oral favipiravir treatment among COVID-19 patients in Nepal.Methods & MaterialsIn this multi-centered randomized, open-labelled phase III clinical trial, we enrolled 18-80 years old, RT-PCR confirmed patients with mild to moderate COVID-19 infection from 9 participating hospitals of Nepal, within 6 days of onset of symptoms. The investigational product (Favipiravir) was compared against placebo in patients with mild infection and against Remdesivir in moderate infection. Patients who met the eligibility criteria were randomly enrolled in the study after taking informed consent. This is a preliminary report of the data analysis.ResultsAt the time of this preliminary data analysis, 90 cases were enrolled in the study including 70 mild and 20 moderate cases (see table). Among the participants with mild COVID19 infection, clinical improvement was noted in 30 (78.9%) and 27 (84.4%) patients who received Favipiravir and placebo, respectively (p=0.78). While among the participants with moderate infection, 9 (81%) and 8 (88.9%) patients who received Favipiravir and Remdesivir, respectively, had clinical improvement (p=1). Patients tolerated Favipiravir well with only 3 (6.12 %) patients showing adverse events, which were mainly elevated liver function test & uric acid level, both considered minor. None of the patients receiving placebo or remdesivir reported any adverse events.ConclusionThe investigational product has been tolerated well by this group of patients with only mild and reversible side effects in 6.12 % cases. The outcomes between the study groups were comparable.

EFFECTS OF HYDROXYCHLOROQUINE PLUS FAVIPIRAVIR TREATMENT ON THE CLINICAL COURSE AND BIOMARKERS IN HOSPITALIZED COVID-19 PATIENTS WITH PNEUMONIA.

The novel coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations, the most common serious clinical manifestation of the coronavirus infection being pneumonia. Unfortunately, the optimal treatment approach is still uncertain. However, many studies have been conducted on the effectiveness of several medications in the treatment of COVID-19 infection. The aim of this study was to evaluate the effectiveness of the hydroxychloroquine (HCQ) + favipiravir (FAV) treatment regimen and HCQ alone by comparing the patient's clinical response and laboratory results on the fifth day of treatment in patients hospitalized due to COVID-19 infection. This retrospective cohort study was conducted in Malatya Training and Research Hospital between March 2020 and July 2020. The study included 69 patients with confirmed COVID-19 with pneumonia. The patients were divided into 2 groups, those receiving HCQ alone and those receiving the HCQ + FAV combination. A total of 69 patients were included in the study, and the mean age was 60.09±15.56 years. A statistically significant decrease was observed in C-reactive protein (CRP) levels, at the end of the fifth day, in patients who received HCQ + FAV treatment (p=0.002), whereas there was no decrease in CRP levels in patients who received HCQ treatment alone. In addition, an increase in lymphocyte count and a better fever response was observed at the end of the fifth day in patients who received HCQ + FAV (p=0.008). However, there was no statistical difference between both treatment regimens in terms of hospital stay and treatment results (p=0.008, p=0.744, p=0.517). Although the combination of HCQ + FAV treatment was observed to be effective on CRP levels and fever response in patients with COVID-19 pneumonia, there was no difference in terms of hospital stay and discharge.

Effect of low and high dose of favipiravir on ovarian and reproductive function in female rats: Biochemical and histopathological evaluation.

Favipiravir is a drug which shows antiviral activity by inhibiting RNA-dependent RNA polymerase. Favipiravir causes severe adverse effects at high doses. The aim of this study was to investigate the effects of low and high dose favipiravir on ovarian and reproductive function in female rats. The rats were divided into three groups: HG group (healthy rats), FAV-100 group (rats administered 100 mg/kg favipiravir), and FAV-400 group (rats administered 400 mg/kg favipiravir) with 12 rats in each group. Favipiravir was administered orally twice daily for 1 week. Six rats from each group were euthanized and their ovaries were removed. Oxidative and antioxidant parameters were measured in ovarian tissues and examined histopathologically. The remaining animals were kept to breed. Animals receiving favipiravir had increased oxidant content, decreased antioxidant activity, decreased histopathological damage, infertility, and gestational delay. Favipiravir treatment should be used with caution, especially in women of reproductive age.

A Randomized Controlled Trial of Combined Ivermectin and Zinc Sulfate versus Combined Hydroxychloroquine, Darunavir/Ritonavir, and Zinc Sulfate among Adult Patients with Asymptomatic or Mild Coronavirus-19 Infection.

Introduction:Ivermectin, hydroxychloroquine (HQ), and darunavir/ritonavir are widely prescribed as an oral treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection despite their uncertainty of clinical benefit. The objective is to determine the safety and the efficacies of two treatment regimens against SARS-CoV-2 infection.Methods:We conducted an open-labeled, randomized, controlled trial to compare the efficacy between a 3-day course of once-daily high-dose oral ivermectin plus zinc sulfate (Group A) and a combination of HQ, darunavir/ritonavir, and zinc sulfate (HQ + antiretroviral, Group B) for 5 days in asymptomatic or mild SARS-CoV-2 infection. The study period was between December 2020 and April 2021.Results:Overall, 113 patients were randomized and analyzed (57 patients in Group A and 56 patients in Group B). The median duration to achieve the virological outcome of either undetected or cycle threshold (Ct) for N gene of SARS-CoV-2 by real-time polymerase chain reaction was 6 days (95% confidence interval [CI] 5.3–6.7) versus 7 days (95% CI: 5.4–8.6) in Group A and Group B, respectively (P = 0.419) in the modified intention-to-treat population. All patients were discharged from hospital quarantine as planned. Two patients in Group A and one patient in Group B were considered clinically worsening and received 10 days of favipiravir treatment. There was no serious adverse event found in both groups.Conclusion:We demonstrated that both treatment regimens were safe, but both treatment regimens had no virological or clinical benefit. Based on this result and current data, there is no supporting evidence for the clinical benefit of ivermectin for coronavirus-19.

US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19.

BackgroundFavipiravir is used to treat influenza, and studies demonstrate that it has antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe performed a randomized, open-label, multicenter, phase 2 proof-of-concept trial of favipiravir in hospitalized adult patients with polymerase chain reaction (PCR)–positive coronavirus disease 2019 (COVID-19). Patients were randomized to standard of care (SOC) or favipiravir treatment (1800mg per os twice a day [b.i.d.] on day 1, followed by 1000mg b.i.d. for 13 days). The primary end point was time to viral clearance on day 29.ResultsFifty patients were enrolled and stratified by disease severity (critical disease, severe disease, or mild to moderate disease). Nineteen patients were censored from the event of viral clearance based on being SARS-CoV-2 PCR-negative at the study outset, being PCR-positive at day 29, or because of loss to follow-up. Data from the 31 remaining patients who achieved viral clearance show enhanced viral clearance in the favipiravir group compared with the SOC group by day 29, with 72% of the favipiravir group and 52% of the SOC group being evaluable for viral clearance through day 29. The median time to viral clearance was 16.0 days (90% CI, 12.0 to 29.0) in the favipiravir group and 30.0 days (90% CI, 12.0 to 31.0) in the SOC group. A post hoc analysis revealed an effect in the subgroup of patients who were neutralizing antibody–negative at randomization. Treatment-emergent adverse events were equally distributed between the groups.ConclusionsWe demonstrate that favipiravir can be safely administered to hospitalized adults with COVID-19 and believe that further studies are warranted.ClinicalTrials.gov registrationNCT04358549.

Favipiravir Inhibits Mayaro Virus Infection in Mice.

Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.