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

Marvin R McCreary, Patrick M Schnell, Dale A Rhoda, Marvin R McCreary, Patrick M Schnell, Dale A Rhoda

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.

Conflict of interest statement

Conflicts of Interest:

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of potential resveratrol effects on virus and host (See Figure key) Figure 1 Key 1. Inhibits Spike protein to ACE2 binding 4,5 2. Inhibits transcription of viral proteases (Mpro and PLpro) 6–9 3. Inhibits RNA-dependent RNA polymerase 10 4. Inhibits proinflammatory cytokines 11–13 5. Inhibits platelet aggregation 14,15 6. Activates endothelial Nitric Oxide (antiviral and vasoprotective) 16–18 7. Inhibits proinflammatory NF-kB 19 8. Inhibits proinflammatory Th-17 T-cells 20 9. Stimulates the production of glutathione in lung epithelium 21–23
Figure 2
Figure 2
CONSORT Diagram

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