Background As an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients. Method Forty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively. Result Our primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant ( P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant ( P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin. Conclusion Nano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.

In the course of the coronavirus disease 2019 (COVID‐19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID‐19 patients compared with the control group. Forty COVID‐19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real‐time polymerase chain reaction, and enzyme‐linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR‐related orphan receptor gamma [RORγt], IL‐17, and IL‐23), and the secretion levels of IL‐17 and IL‐23 cytokines in COVID‐19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor‐β [TGF‐β], and IL‐10), and cytokine secretion levels (TGF‐β and IL‐10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL‐17/IL‐10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019‐n‐CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID‐19‐dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.

In novel coronavirus disease 2019 (COVID‐19), the increased frequency and overactivation of T helper (Th) 17 cells and subsequent production of large amounts of proinflammatory cytokines result in hyperinflammation and disease progression. The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of Th17 cells in mild and severe COVID‐19 patients. In this study, 40 severe COVID‐19 intensive care unit‐admitted patients and 40 patients in mild condition were included. The frequency of Th17 cells, the messenger RNA expression of Th17 cell‐related factors (RAR‐related orphan receptor γt, interleukin [IL]‐17, IL‐21, IL‐23, and granulocyte‐macrophage colony‐stimulating factor), and the serum levels of cytokines were measured in both nanocurcumin and placebo‐treated groups before and after treatment. A significant decrease in the number of Th17 cells, downregulation of Th17 cell‐related factors, and decreased levels of Th17 cell‐related cytokines were found in mild and severe COVID‐19 patients treated by nanocurcumin compared to the placebo group. Moreover, the abovementioned parameters were significantly decreased in the nanocurcumin‐treated group after treatment versus before treatment. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID‐19 patients. Hence, it could be considered as a potential modulatory compound in improving the patient's inflammatory condition.

Introduction: Bromhexine is a potential therapeutic option in COVID-19, but no data from a randomized clinical trial has been available. The present study aimed to evaluate the efficacy of bromhexine in intensive care unit (ICU) admission, mechanical ventilation, and mortality in patients with COVID-19. Methods: An open-label randomized clinical trial study was performed in Tabriz, North-West of Iran. They were randomized to either the treatment with the bromhexine group or the control group, in a 1:1 ratio with 39 patients in each arm. Standard therapy was used in both groups and those patients in the treatment group received oral bromhexine 8 mg three times a day additionally. The primary outcome was a decrease in the rate of ICU admissions, intubation/mechanical ventilation, and mortality. Results: A total of 78 patients with similar demographic and disease characteristics were enrolled. There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006), intubation (1 out of 39 vs. 9 out of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects. Conclusion: The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy. Altogether, the verification of our results on a larger scale and different medical centers is strongly recommended. Trial Registration: IRCT202003117046797N4; https://irct.ir/trial/46969.

In Coronavirus disease 2019 (COVID-19), a decreased number of regulatory T (Treg) cells and their mediated factors lead to a hyperinflammatory state due to overactivation of the inflammatory cells and factors during the infection. In the current study, we evaluated the Nanocurcumin effects on the Treg cell population and corresponding factors in mild and severe COVID-19 patients. To investigate the Nanocurcumin effects, 80 COVID-19 patients (40 at the severe stage and 40 at the mild stage) were selected and classified into Nanocurcumin and placebo arms. In both the Nanocurcumin and placebo groups, the Treg cell frequency, the gene expression of Treg transcription factor forkhead box P3 (FoxP3), and cytokines (IL-10, IL-35, and TGF-β), as well as the serum levels of cytokines were measured before and after treatment. In both mild and severe COVID-19 patients, Nanocurcumin could considerably upregulate the frequency of Treg cells, the expression levels of FoxP3, IL-10, IL-35, and TGF-β, as well as the serum secretion levels of cytokines in the Nanocurcumin-treated group compared to the placebo group. The abovementioned factors were remarkably increased in the post-treatment with Nanocurcumin before pre-treatment conditions. By contrast, it has been observed no notable alterations in the placebo group. Our findings revealed the SinaCurcumin® effective function in a significant increase in the number of Treg cells and their mediated factors in the Nanocurcumin group than in the placebo group in both mild and severe patients. Hence, it would be an efficient therapeutic agent in rehabilitating COVID-19 infected patients.