Background
Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.
Methods
Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.
Results
Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.
Conclusions
Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
This research investigates the extraction of fulvic acid (FA) from Hami lignite from Xinjiang, China, by microwave-hydrogen peroxide and microwave-hydrogen peroxide-formic acid methods. The effects of reaction time, oxidant concentration, oxygen-coal ratio and microwave power on FA yield are determined. Sulfuric acid-acetone was applied to purify the primary FA products. The results indicate that the oxidant concentration is a sensitive factor affecting the yield of FA, while reaction time has little effect. Formic acid can promote the extraction of FA from lignite by hydrogen peroxide, and under optimal experimental conditions, the yields of FA were 5.34% and 9.13%, respectively. UV-Vis analysis shows that FA has a lower aromaticity and degree of carbonyl conjugation in the presence of formic acid. Additionally, Fourier transform infrared spectroscopy was used to characterize the purified FA. The results show that the benzene rings of FA have one, two, three and four substitutions, oxygen-containing functional groups containing -COOH, C=O, -OCH 3 , CÀ OÀ C, Ar-OH, and R-OH and, furthermore, primary oxygen-containing functional groups consisting of C=O and C-OH. The aliphatic functional groups contain symmetrical and anti-symmetrical stretching vibrations of -CH 2 and -CH 3 . Finally, the hydrogen bonds are mainly composed of phenolic hydroxyls and alcoholic hydroxyls, while some hydrogen carboxylate is present.
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