Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

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.

Evaluation of Hepatic, Renal and Cardiac Diagnostic Markers in Patients With Severe COVID-19

SARS-CoV-2 that causes Coronavirus disease 2019 (COVID-19) was first known in Wuhan, China, in December 2019. The aim of this study was to evaluate the level of common hepatic, renal, and cardiac diagnostic markers in hospitals in patients with severe COVID 19. In this study, 259 patients with symptoms of severe COVID-19 and a positive RT-PCR assay of nasopharyngeal samples were enrolled. Inclusion criteria are positive for COVID-19 patients at the diagnosis of an infectious disease physician. Diagnostic markers of liver, kidney, and heart were evaluated by age and gender. In this study, 48.3% of patients severe with COVID-19 were male, and 51.7% were female. The mean of markers such as LDH, Direct Bilirubin, SGOT, SGPT, D-dimer was higher than normal, which was observed in men more than women. The mean of CK-MB also was higher than normal, which was observed in women more than men. The highest mean of markers was seen in the older ages. The mean of BUN was observed in the age range of 55-64 years and above 65 years above normal. But the mean of CPK, creatinine, potassium and alkaline phosphatase were normal. The results of the present study showed an increase in the level of some of the most important diagnostic markers of hepatic, renal, and cardiac in patients with COVID 19. This increase was greater in some markers, including SGOT, SGPT, Direct bilirubin, LDH, D-dimer, in men than in women, and more in older patients. [ FROM AUTHOR] Copyright of Acta Medica Iranica is the property of Tehran University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all Abstracts.)

Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIMS: The current study was done to examine the efficacy of naproxen in the management of patients with COVID-19 infection. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was done on hospitalized adult patients with confirmed COVID-19 infection. Patients were randomly assigned to receive either naproxen (two capsules per day each containing 500 mg naproxen sodium) or placebo (containing starch) for five days along with the routine treatment that was nationally recommended for COVID-19 infection. Clinical symptoms of COVID-19 infection, the time to clinical improvement, blood pressure, laboratory parameters, and death due to COVID-19 infection were considered as the outcome variables in the present study. RESULTS: Treatment with naproxen improved cough and shortness of breath in COVID-19 patients; such that, compared with placebo, naproxen intake was associated with 2.90 (95% CI: 1.10-7.66) and 2.82 (95% CI: 1.05-7.55) times more improvement in cough and shortness of breath, respectively. In addition, naproxen administration resulted in a significant increase in mean corpuscular volume (MCV) and had a preventive effect on the reduction of systolic blood pressure in COVID-19 patients. CONCLUSION: Treatment with naproxen can improve cough and shortness of breath in COVID-19-infected patients. Further studies are required to confirm our findings.

The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19.

OBJECTIVES: Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. METHODS: Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT-PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. RESULTS: Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04-0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1-12.1, P < 0.01). CONCLUSIONS: Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.