Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders

Abstract

Coagulation disorders, endotheliopathy and inflammation are the most common hallmarks in SARS-CoV-2 infection, largely determining COVID-19’s outcome and severity. Dysfunctions of endothelial cells and platelets are tightly linked in contributing to the systemic inflammatory response that appears to be both a cause and a consequence of COVID-19-associated coagulation disorders and thrombotic events. Indeed, elevated levels of circulating inflammatory cytokines are often associated with abnormal coagulation parameters in COVID-19 patients. Although treatments with low molecular weight heparin (LMWH) have shown beneficial effects in decreasing patient mortality with severe COVID-19, additional therapeutic strategies are urgently needed. Utilizing the anti-inflammatory and anti-thrombotic properties of natural compounds may provide alternative therapeutic approaches to prevent or reduce the risk factors associated with pre-existing conditions and comorbidities that can worsen COVID-19 patients’ outcomes. In this regard, resveratrol, a natural compound found in several plants and fruits such as grapes, blueberries and cranberries, may represent a promising coadjuvant for the prevention and treatment of COVID-19. By virtue of its anti-thrombotic and anti-inflammatory properties, resveratrol would be expected to lower COVID-19-associated mortality, which is well known to be increased by thrombosis and inflammation. This review analyzes and discusses resveratrol’s ability to modulate vascular hemostasis at different levels targeting both primary hemostasis (interfering with platelet activation and aggregation) and secondary hemostasis (modulating factors involved in coagulation cascade).

Role of Resveratrol in Prevention and Control of Cardiovascular Disorders and Cardiovascular Complications Related to COVID-19 Disease: Mode of Action and Approaches Explored to Increase Its Bioavailability

“…The hypercoagulation and thromboembolic complications correlate with a more severe course of COVID-19 and high thromboembolism risk of COVID-19 has shown to be directly associated with a higher risk of mortality according to a systematic review and meta-analysis [ 233 ]. With its proven anti-thrombotic effects, resveratrol was proposed as an adjunct treatment for slowing and ameliorating vascular thrombosis in the course of COVID-19 [ 234 ].…”

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

“…Many patients infected with SARS-CoV-2 have a severe proinflammatory state linked with characteristic coagulopathy and endotheliopathy [ 113 ], with the SARS-CoV-2 endothelial status made distinct by platelet activation, as well as increased levels of Von Willebrand factor and factor VIII [ 114 , 115 ]. Coagulopathy, due to blockage of blood vessels following thrombus formation, is seen in severe SARS-CoV-2 infections as a result of platelet hyperactivity and aggregation [ 113 ]. In this context, the protective antiplatelet aggregation role of resveratrol, a polyphenol, can be utilized in the management of SARS-CoV-2 infection, via its various mechanisms of action.…”

“…As discussed earlier, COVID-19 is associated with a hyperinflammatory and prothrombotic state, with increases in fibrin, fibrin degradation products, fibrinogen, and D-dimers [ 12 , 14 , 15 , 16 , 17 ], as well as proinflammatory cytokines including IL-1, IL-6, and tumor necrosis factor-α [ 113 ]; therefore, the administration of anticoagulation therapy in COVID-19 positive CVD patients must be carefully monitored. Additionally, as indications of drug treatment include prophylaxis against stroke and embolism [ 5 , 14 , 19 ], it is crucial for patients to be able to continue treatment safely if infected with SARS-CoV-2.…”

Potentials of Antitussive Traditional Persian Functional Foods for COVID-19 Therapy†

“…Resveratrol has antioxidant and immune-stimulatory properties (Ramdani and Bachari, 2020;Santos et al, 2021). Also, by virtue of its anti-inflammatory and anti-thrombotic properties, resveratrol is expected to lower the mortality rate of COVID-19 disease (Giordo et al, 2021).…”