Resveratrol and Copper for treatment of severe COVID-19: an observational study (RESCU 002)

Abstract

Background To be universally applicable in treatment of severe COVID-19, novel therapies, especially those with little toxicity and low cost, are urgently needed. We report here the use of one such therapeutic combination involving two commonly used nutraceuticals, namely resveratrol and copper in patients with this disease. This study was prompted by pre-clinical reports that sepsis-related cytokine storm and fatality in mice can be prevented by oral administration of small quantities of resveratrol and copper. Since cytokine storm and sepsis are major causes of death in severe COVID-19, we retrospectively analyzed outcomes of patients with this condition who had received resveratrol and copper. Methods & Findings Our analysis comprised of 230 patients with severe COVID-19 requiring inhaled oxygen who were admitted in a single tertiary care hospital in Mumbai between April 1 and May 13 2020. Thirty of these patients received, in addition to standard care, resveratrol and copper at doses of 5.6 mg and 560 ng, respectively, orally, once every 6 hours, until discharge or death. These doses were based on our pre-clinical studies, and were nearly 50 times and 2000 times less, respectively, than those recommended as health supplements. A multivariable-adjusted analysis was used to model the outcome of death in these patients and evaluate factors associated with this event. A binary logistic regression analysis was used, with age, sex, presence of comorbidities and receipt of resveratrol-copper as covariates. Data were updated as of May 30 2020. The number of deaths in resveratrol-copper and standard care only groups were 7/30 (23.3%, 95% CI 8.1%-38.4%) and 89/200 (44.5%, 95% CI 37.6%-51.3%), respectively. In multivariable analysis, age >50 years [odds ratio (OR) 2.558, 95% CI 1.454-4.302, P=0.0011] and female sex (OR 1.939, 95% CI 1.079-3.482, P=0.0267) were significantly associated, while presence of co-morbidities was not significantly associated (OR 0.713, 95% CI 0.405-1.256, P=0.2421) with death. There was a trend towards reduction in death in patients receiving resveratrol-copper (OR 0.413, 95% CI 0.164-1.039, P= 0.0604). Conclusions We provide preliminary results of a novel approach to the treatment of severe COVID-19 using a combination of small amounts of commonly used nutraceuticals, which is non-toxic and inexpensive, and therefore could be widely accessible globally. The nearly two-fold reduction in mortality with resveratrol-copper observed in our study needs to be confirmed in a randomized controlled trial.

Consumption of Phenolic-Rich Food and Dietary Supplements as a Key Tool in SARS-CoV-19 Infection

“…Additionally, the co-incubation of cells with the SARS-CoV-2 and a concentration of 50 µM of resveratrol for one hour showed to cause a reduction by 64% in virus infection, indicating a possible blockage of the virus’s ability to enter host cells [ 79 ]. In accordance with that, it has also been reported that the daily intake of 3 doses of 5.6 mg of resveratrol by COVID-19 patients showed a 50% reduction in the percentage of deaths in the treated group [ 80 ].…”

Potential Natural Products Against Respiratory Viruses: A Perspective to Develop Anti-COVID-19 Medicines

“…In one study, a nearly two-fold reduction in mortality following treatment with resveratrol-copper was observed. In this study thirty patients with severe COVID-19 received, in addition to standard care, resveratrol ( 69 ) and copper at doses of 5.6 mg and 560 ng, respectively orally, once every 6 h, until discharge or death ( Mittra et al, 2020 ). Lianhua Qingwen prescription (capsules or granules) is an innovative patented Chinese medicine that is composed of 11 herbs with gypsum and menthol, and this preparation had antiviral activities against viral respiratory infections.…”

Experimental Pharmacotherapy for COVID-19: The Latest Advances

“…Even if they are attractive for their very limited toxicity, data are not sufficient to introduce further investigations in this literature review. [112][113][114]…”