favipiravir and Body-Weight

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.

Topics: Adult; Antiviral Agents; Body Weight; COVID-19 Drug Treatment; Dexamethasone; Female; Humans; Influenza, Human; Male; Middle Aged; Pandemics; Retrospective Studies

Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.

Topics: Acids, Carbocyclic; Amides; Animals; Antiviral Agents; Body Weight; Cyclopentanes; Dogs; Drug Resistance, Viral; Drug Synergism; Drug Therapy, Combination; Female; Guanidines; Influenza A Virus, H1N1 Subtype; Lung; Madin Darby Canine Kidney Cells; Mice; Mice, Inbred DBA; Orthomyxoviridae Infections; Oseltamivir; Pyrazines; Survival Rate

A mouse model of western equine encephalitis (WEE) was characterized for use in antiviral studies. Virus was detected in several tissues, most notably an average titer of 9.5+/-1.1 log(10) 50% cell culture infectious doses (CCID(50))/g tissue in the brains of infected animals. Signs of WEE included limb weakness, paralysis, involuntary spasms or extension of limbs, clenching of paws, hunching, ruffling of fur, and eye exudates, many of which are indicative of neurological disease. The pyrazinecarboxamide derivative, T-705, was found to be active in Vero cells against WEE virus (WEEV) with an 90% effective concentration (EC(90)) of 49microg/ml (selective index [SI]>20). Treatment with T-705 in this WEE mouse model resulted in significant improvement in survival and mean day to death after oral treatment administered twice a day for 7 days at a dose of 400mg/(kgd). Virus titer in the brain was not significantly reduced, despite a 1-log reduction in average brain titer in treated animals on 4dpi. Signs of disease were relatively mild in treated animals, but were not eliminated. Treatment with T-705 improved morbidity and mortality of WEEV-infected mice, further illustrating the broad-spectrum activity of T-705 in the treatment of RNA viruses.

Topics: Administration, Oral; Amides; Animals; Antiviral Agents; Body Weight; Chlorocebus aethiops; Disease Models, Animal; Encephalomyelitis, Western Equine; Mice; Mice, Inbred C57BL; Pyrazines; Serum; Survival Analysis; Vero Cells