Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19)

Abstract

Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N=105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia and pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female) (or their surrogates). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04-3.10), COVID-related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18-1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16-1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06-15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events. A larger trial could determine efficacy.TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020

Sustained Release of Co-Amorphous Matrine-Type Alkaloids and Resveratrol with Anti-COVID-19 Potential

“…The powder samples contained 50 mg of matrine, oxymatrine, and sophoridine were accurately weighed and compressed at a pressure of 6 MPa to obtain tablets with 8 mm diameter for the release experiments. The release experiments were carried out in a dissolution tester (RC-6, Tianguang, Tianjin, China) at a rotational speed of 50 rpm in PBS (100 mL, pH = 6.8) as a dissolution medium at 37 ± 0.5 • C. At the predetermined time points (1,5,10,20,30,60,120,240,360, and 720 min), the dissolution medium (1 mL) was acquired and the equal volume of fresh PBS was supplemented. The acquired sample was next filtrated through a polycarbonate filter (0.22 µm), diluted with fresh PBS, and analyzed by HPLC.…”

“…Oxymatrine (OMAR) and sophoridine (SPD, Scheme 1) are matrine-type alkaloids isolated from S. flavescens Ait with promising biological activities [16,17], including antiviral activity [18,19]. Resveratrol (RES) is a plant polyphenol, which has also been used to treat COVID-19 patients with mild symptoms or as adjuvant supplements due to its anti-SARS-CoV-2 and anti-inflammatory activities [20,21]. However, matrine was given to COVID-19 patients via intravenous infusion [9], suggesting its poor pharmacokinetic properties, which may result in poor patient compliance and persistence, as well as unsatisfactory outcomes.…”

“…Oxymatrine (OMAR) and sophoridine (SPD, Scheme 1 ) are matrine-type alkaloids isolated from S. flavescens Ait with promising biological activities [ 16 , 17 ], including antiviral activity [ 18 , 19 ]. Resveratrol (RES) is a plant polyphenol, which has also been used to treat COVID-19 patients with mild symptoms or as adjuvant supplements due to its anti-SARS-CoV-2 and anti-inflammatory activities [ 20 , 21 ].…”

The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 – A formulator’s perspective

“…Recently a randomized double-blind placebo-controlled proof-of-concept trial of resveratrol demonstrated that the resveratrol group had a lower incidence of hospitalization, COVID-related emergency room visits, and pneumonia compared to the placebo group of outpatients with mild COVID-19 [49] .…”

Redox Homeostasis and Immune Alterations in Coronavirus Disease-19

“…In a placebo-controlled cross-over study, resveratrol supplementation in obese men reduced the expression of ACE2 in adipose tissue, suggesting that this compound could reduce SARS-CoV-2 diffusion [ 150 ]. A randomized placebo-controlled phase 2 trial showed that oral supplementation of resveratrol in COVID-19 outpatients presented with lower incidence of pneumonia and hospitalization [ 151 ].…”