SARS-CoV-2 variation observed within a representative participant is shown in Supplementary Figure 5. Residual nasal swabs had a mean qPCR CT of 22.3 and a mean depth of coverage of 1738X (95.1% of the genome with depth of coverage >10X). We included 112 PCR-positive nasal samples from 73 study participants (36 placebo, 37 favipiravir) that met our quality and coverage filters, including >1 longitudinal sample from 36 participants (18 placebo, 18 favipiravir). We used a p-value threshold of 0.05 to identify predictors significantly associated with within-host viral diversity. We fit independent linear models for the number of iSNVs, standardized number of iSNVs, number of transitions, and standardized number of transitions with study day and treatment group as predictor variables in the R package stats. To assess favipiravir’s impact on SARS-CoV-2 within-host diversity, we tested if the number of iSNVs, transitions, and/or either iSNVs and transitions standardized by the total number of bases sequenced in a sample differed between the treatment arms on day 5 using one-sided two-sample t-tests with the R package rstatix. We predicted that favipiravir would impact viral diversity by study day 5 and result in a higher rate of transition mutations. We used the nfcore/viralrecon v.2.3dev bioinformatic pipeline to perform variant calling and to generate consensus sequences from raw reads (Supplementary Methods). Patients also completed electronic daily symptom surveys and recorded temperature and oxygen saturation using study-provided devices all data was collected using REDCap Cloud version 1.6 (REDCap Cloud, Encinitas, California). Patients self-collected daily anterior nasal swabs on days 1-10, 14, 21, and 28 and submitted them directly for RT-PCR testing with an assay that targeted the viral nucleocapsid gene’s N1 and N3 regions (Quest Diagnostics, Secaucus, New Jersey). Anti-SARSCoV-2 serology was performed using a virus plaque reduction neutralization assay (Viroclinics Biosciences, Rotterdam, The Netherlands). Staff-collected OP specimens underwent a reverse-transcription polymerase chain reaction assay (RT-PCR) (Viroclinics Biosciences, Rotterdam, The Netherlands). We followed participants for 28 days and performed a clinical assessment and collected oropharyngeal (OP) swabs and blood samples at each visit. Favipiravir and placebo tablets were identical in appearance to maintain blinding. Participants received placebo or favipiravir at doses of 1800 mg BID on Day 1, then 800mg BID on days 2-10. We evaluated favipiravir’s efficacy in reducing viral shedding duration and improving symptoms in outpatients with uncomplicated COVID-19. Despite limited data, favipiravir was approved for use in patients with COVID-19 in some countries. Since 2014, favipiravir has been used in Japan and China for patients with drug-resistant influenza and boasts an established, well-characterized safety profile, making it an attractive potential therapeutic option for COVID-19.Įarly data from some open-label trials suggested that favipiravir improved clinical and/or virologic outcomes in patients with COVID-19. In its active form, favipiravir is incorporated into nascent viral RNA by error-prone viral RdRp and disrupts RNA synthesis directly by chain termination or accumulation of deleterious mutations in the SARS-COV-2 genome. Favipiravir is an oral, RNA-dependent RNA polymerase (RdRp) inhibitor with a wide spectrum of activity, including in vitro activity against SARS-CoV2.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |