Evaluation of tumour necrosis factor alpha-stimulated gene-6 and fibroblast growth factor-2 levels in patients diagnosed with multi-system inflammatory syndrome in children.

Investigations are still ongoing about the pathophysiology of multi-system inflammatory syndrome in children, which can progress with serious morbidity and mortality after COVID-19 infection. In this study, we aimed to investigate whether fibroblast growth factor-2 and tumour necrosis factor alpha-stimulated gene-6 levels play a role in the diagnosis of the disease and on cardiac involvement. Twenty-three patients (11 girls, 12 boys) and 26 healthy controls (10 girls, 16 boys) were included in the study. The mean age of the patient and control group was 8.45 ± 2.43 and 10.73 ± 4.27 years, respectively. There was no difference between the fibroblast growth factor-2 and tumour necrosis factor alpha-stimulated gene-6 levels of the patient and control groups. When the patients with myocardial involvement in the patient group were compared with the patients without myocardial involvement in terms of fibroblast growth factor-2 and tumour necrosis factor alpha-stimulated gene-6 levels, no difference was found between these groups. The correlation of fibroblast growth factor-2 and tumour necrosis factor alpha-stimulated gene-6 levels with other laboratory parameters was investigated in the patient group. Fibroblast growth factor-2 was moderately inversely correlated with white blood cell count (r = -0.541, p = 0.008), absolute neutrophil count (r = -0.502, p = 0.015) and C-reactive protein (r = -0.528, p = 0.010). Fibroblast growth factor-2 was strongly inversely correlated with erythrocyte sedimentation rate (r = -0.694, p =<0.001). Our data show that fibroblast growth factor-2 and tumour necrosis factor alpha stimulated gene-6 do not provide sufficient information about diagnosis and cardiac involvement in multi-system inflammatory syndrome in children.

Instant determination of the artemisinin from various Artemisia annua L. extracts by LC-ESI-MS/MS and their in-silico modelling and in vitro antiviral activity studies against SARS-CoV-2.

INTRODUCTION: Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS-CoV-2. OBJECTIVE: The main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS-CoV-2 using molecular modelling. METHODOLOGY: Twenty-one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra-rapid determined artemisinin active molecules by LC-ESI-MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS-CoV-2 virus was assessed by time resolved fluorescence energy transfer (TR-FRET) assay. RESULTS: Artemisinin content in the range 0.062-0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE-2 binding. The 50% effective concentration (EC50 ) of artemisinin against SARS-CoV-2 Spike pseudovirus was found greater than 50 µM (EC45 ) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF-α production on both pseudovirus and lipopolysaccharide (LPS)-induced THP-1 cells were found significant in a dose dependent manner. CONCLUSION: Further studies of these extracts for COVID-19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.

Understanding the pathophysiological changes via untargeted metabolomics in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by a new strain of the coronavirus. There is limited data on the pathogenesis and the cellular responses of COVID-19. In this study, we aimed to determine the variation of metabolites between healthy control and COVID-19 via the untargeted metabolomics method. Serum samples were obtained from 44 COVID-19 patients and 41 healthy controls. Untargeted metabolomics analyses were performed by the LC/Q-TOF/MS (liquid chromatography quadrupole time-of-flight mass spectrometry) method. Data acquisition, classification, and identification were achieved by the METLIN database and XCMS. Significant differences were determined between patients and healthy controls in terms of purine, glutamine, leukotriene D4 (LTD4), and glutathione metabolisms. Downregulations were determined in R-S lactoglutathione and glutamine. Upregulations were detected in hypoxanthine, inosine, and LTD4. Identified metabolites indicate roles for purine, glutamine, LTD4, and glutathione metabolisms in the pathogenesis of the COVID-19. The use of selective leukotriene D4 receptor antagonists, targeting purinergic signaling as a therapeutic approach and glutamine supplementation may decrease the severity and mortality of COVID-19.