ABSTRACT
BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.
Subject(s)
COVID-19 , Sofosbuvir , Adult , Antiviral Agents/therapeutic use , Carbamates , Humans , Imidazoles , Pyrrolidines , SARS-CoV-2 , Sofosbuvir/therapeutic use , Treatment Outcome , Valine/analogs & derivativesABSTRACT
BACKGROUND: The persistence of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RNA in the body fluids of patients with the novel coronavirus disease 2019 (COVID-19) may increase the potential risk of viral transmission. There is still uncertainty on whether the recommended quarantine duration is sufficient to reduce the risk of transmission. This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19. METHODS: In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, 1 week after discharge, and every 2 weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence. RESULTS: The median duration of viral RNA persistence in the nasopharyngeal samples was 8 days from the first positive RT-PCR result upon admission (95% CI 6.91-9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was 7 days (95% CI 6.07-7.93), 6 days (95% CI 4.16-8.41), and 13 days (95% CI 6.96-19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively. CONCLUSION: According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions.