Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients
| Autor: | Jane, Fisher, Tirthankar, Mohanty, Christofer A Q, Karlsson, S M Hossein, Khademi, Erik, Malmström, Attila, Frigyesi, Pontus, Nordenfelt, Johan, Malmstrom, Adam, Linder |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteome HFNO High flow nasal oxygenation MPO Myeloperoxidase Fluorescent Antibody Technique rhDNase Recombinant human Deoxyribonuclease I COVID-19 Corona Virus Disease 2019 NETs Neutrophil extracellular traps Extracellular Traps Severity of Illness Index DNA Deoxyribonucleic acid ECMO Extracorporeal membrane oxygen therapy ARDS Acute respiratory distress syndrome Deoxyribonuclease I Humans Aged Research GGO Glass ground opacity Sputum COVID-19 DNase I Deoxyribonuclease I Blood Proteins Middle Aged Recombinant Proteins Systemic Inflammatory Response Syndrome PADI-4 Peptidyl arginine deiminase IV COVID-19 Drug Treatment CF Cystic fibrosis NE Neutrophil elastase Female |
| Zdroj: | Molecular & Cellular Proteomics : MCP |
| ISSN: | 1535-9484 |
| Popis: | Severe coronavirus disease 2019 (COVID-19) can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hallmark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe patients with COVID-19 reveal high levels of neutrophil extracellular trap (NET) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and lead to acute respiratory distress syndrome. Recombinant human DNase (Pulmozyme; Roche) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated five patients pwith COVID-19 resenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill patients with COVID-19 was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of hemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high-flow oxygen therapy in patients. Targeting NETs using recombinant human DNase may have significant therapeutic implications in COVID-19 disease and warrants further studies. |
| Databáze: | OpenAIRE |
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