Randomized Proof-of-Concept Trial to Evaluate the Safety and Explore the Effectiveness of Resveratrol, a Plant Polyphenol, for COVID-19

Resveratrol is a plant polyphenol (that is sold commercially as a supplement) that might help fight coronavirus as well as help protect the body from the effects of disease (COVID-19) caused by the infection. In this proof-of-concept pilot study we will compare the effects of resveratrol to placebo to assess the safety of the resveratrol and explore effectiveness.

This randomized placebo-controlled trial is for the outpatient treatment of (Coronavirus Disease 2019) COVID-19. The purpose of this trial is to evaluate the safety and explore the effectiveness of resveratrol, a plant polyphenol, being re-purposed for patients with early COVID-19. Published in vitro data supports that this polyphenol inhibits coronavirus replication while separately published in silico (computer molecular docking analysis) reports have identified specific molecular targets of resveratrol against (Severe Acute Respiratory Syndrome - Coronavirus 2) SARS-CoV-2. Animal studies also demonstrate that resveratrol is effective at preventing lung injury and death in certain animal models of viral infections. Furthermore, the products long history as an anti-inflammatory might prevent the cytokine storm that is associated with worse outcomes in COVID-19.

200 subjects, 45 and older, (100 receiving the plant polyphenol, 100 receiving placebo) will be enrolled in study to compare whether taking resveratrol will reduce the rate of hospitalization. Subjects will take capsules 4 times a day for a minimum of 7 days (up to 15 days depending on duration of symptoms) plus both groups will receive Vitamin D3 100,000 IU to augment the effects of resveratrol. Resveratrol will be given as 1gm 4 times per day. Placebo tablets will contain brown rice flour in visually identical capsules. The primary outcome measure for this trial is reduction in hospitalization at 21 days from enrollment.

Eligibility Criteria:
Inclusion Criteria:

* Outpatients who test positive for infection with SARS-CoV-2.
* Age ≥45 years
* Mild COVID-19 based on World Health Organization (WHO) Baseline Severity Categorization
* Symptom duration ≤ 10 days, or \<72 hours of new respiratory symptoms.
* Patient must have access to the internet or a smartphone to complete surveys.
* English-speaking patients

Exclusion Criteria:

* Diagnosed or suspected cognitive impairment that would prevent the patient from cooperating with study procedures, as judged by the screening clinician
* Asymptomatic patients (e.g. patients who were screened without symptoms but tested positive)
* Known or suspected liver disease or Hepatitis C
* Known kidney disease with estimate Glomerular Filtration Rate (eGFR) \<60
* Patients on warfarin, Novel Oral Anticoagulants (NOACs), HIV Protease Inhibitors, immunosuppressants, hydroxychloroquine/chloroquine, and other medication with a narrow therapeutic window.
* Allergy to grapes or rice.
* Co-morbidities with a high likelihood of hospitalization within 30 days (e.g., current cancer treatment, severe Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF))
* Currently pregnant
* Hospitalization