Mohammad-Reza Mahmoudian-Sani
1 
, Ali Saeedi Boroujeni
2,3 , Ali Khodadadi
2 , Sheyda Houshmandfar
2 , Sima Tahmaseby Gandomkari
1 , Arash Alghasi
1* 1 Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Immunology Today, Universal Scientific Education and Research Network (USERN), Tehran, Iran
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 126 million people worldwide and deaths exceed two million. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing coronavirus disease 2019 (COVID-19) immunopathogenesis have remained uncertain. Severe COVID-19 is associated with a cytokine storm, chronic inflammation, neutrophilia, lymphocyte dysfunction, lymphopenia, reduction in T-lymphocytes and natural killer (NK) cells, disruption in viral clearance, and neutrophil/macrophage infiltration in the lungs. In many cases, patients develop acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and/or multiple-organ dysfunction syndrome (MODS). Resveratrol reduces the expression of inflammasome activators such as thioredoxin-interacting protein (TXNIP) and nuclear factor erythroid 2 (NrF2) and increases that of the inflammasome inhibitor, i.e., NAD-dependent deacetylase sirtuin-1 (SIRT1). Resveratrol is able to inhibit the production of reactive oxygen species (ROS) and the activation of inducible nitric oxide synthases (iNOS). It affects signaling pathways including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-ĸB) thereby further inhibiting inflammasomes. Because of its anti-inflammasome, anti-inflammatory, and anti-oxidant effects and considering the key role of inflammation and cytokine storm in disease severity and poor patient outcomes, it is concluded that resveratrol can be useful in the treatment of COVID-19. Given the persistence of the COVID-19 pandemic and the challenges of extensive vaccination in all countries, it is important to achieve more effective treatments to decrease the mortality rate and severity of severe injuries following COVID-19. Given all the effects reviewed in this article, resveratrol at a dose of up to 600 mg per day can be exploited as a potential adjunctive therapy for COVID-19 patients.