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.

The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

This study was carried out to determine the effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double-blind, placebo-controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (ß [difference in the mean of outcomes measures between treatment groups] -0.56 cm; 95% CI, -0.92, -0.20; p = 0.003), width (ß -0.35 cm; 95% CI, -0.64, -0.05; p = 0.02) and depth (ß -0.18 cm; 95% CI, -0.33, -0.02; p = 0.02). In addition, co-supplementation led to a significant reduction in fasting plasma glucose (ß -13.41 mg/dL; 95% CI, -20.96, -5.86; p = 0.001), insulin (ß -1.45 µIU/ml; 95% CI, -2.37, -0.52; p = 0.003), insulin resistance (ß -0.60; 95% CI, -0.99, -0.20; p = 0.003) and HbA1c (ß -0.32%; 95% CI, -0.48, -0.16; p < 0.003), and a significant elevation in insulin sensitivity (ß 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (ß -10.08 mg/dL; 95% CI, -19.70, -0.46; p = 0.04), LDL-cholesterol (ß -5.88 mg/dL; 95% CI, -11.42, -0.34; p = 0.03), high sensitivity C-reactive protein (hs-CRP) (ß -3.42 mg/L; 95% CI, -4.44, -2.41; p < 0.001) and malondialdehyde (MDA) (ß -0.30 µmol/L; 95% CI, -0.45, -0.15; p < 0.001), and increased HDL-cholesterol (ß 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (ß 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co-supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL- and HDL-cholesterol, hs-CRP, TAC, and MDA levels.