SARS-CoV-2 is a betacoronavirus causing severe inflammatory pneumonia, so that excessive inflammation is considered a risk factor for the disease. According to reports, cytokine storm is strongly responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Phylogenetic findings show more similarity of the SARS-CoV-2 virus with bat coronaviruses, and less with SARS-CoV. Quercetin is a carbohydrate-free flavonoid that is the most abundant flavonoid in vegetables and fruits and has been the most studied to determine the biological effects of flavonoids. Inflammasomes are cytosolic multi-protein complexes assembling in response to cytosolic PAMP and DAMPs, whose function is to generate active forms of cytokines IL-1β and IL-18. Activation or inhibition of the NLRP3 inflammasome is affected by regulators such as TXNIP, SIRT1 and NRF2. Quercetin suppresses the NLRP3 inflammasome by affecting these regulators. Quercetin, as an anti-inflammatory, antioxidant, analgesic and inflammatory compound, is probably a potential treatment for severe inflammation and one of the main life-threatening conditions in patients with COVID-19.

Background : Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19).Aim of the study. To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19. Methods : This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020–June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. Results : A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups. Conclusions : Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

, the SARS-CoV-2 virus has infected more than 27 million people and left more than 800 000 victims. According to statistics, a high percentage of patients with COVID-19 recover and only a small percentage of them succumb to death. Studies have documented the important role of the immune system in determining the fate of COVID-19 patients. Observations have so far shown that destructive and severe inflammation is the leading cause of death in patients with COVID-19. 1 Significant increases in the levels of inflammatory cytokines (TNF, IL-1β, IL-6, IL-8), colony-stimulating factors (G-CSF and GM-CSF) and inflammatory chemokines (MCP1, IP10 and MIP1α) and the destructive role of inflammatory monocytes and macrophages indicate the role of inflammation in COVID-19 pathogenesis. 2,3 Acute respiratory distress syndrome (ARDS) and cytokine storm are the two main causes of severe COVID-19. 1