Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients

• DOI: 10.1016/j.mcpro.2021.100113
• Publication Date: 2021-06-15T21:40:38Z
• Authors: Jane Fisher; Tirthankar Mohanty; Christofer A.Q. K...; S. M. Hossein Kha...; Erik Malmström; Attila Frigyesi; Pontus Nordenfelt; Johan Malmstrom; Adam Linder
• Keywords: Male; 0301 basic medicine; Proteome; Research; Sputum; COVID-19; Fluorescent Antibody Technique; Blood Proteins; Middle Aged; Extracellular Traps; Severity of Illness Index; Recombinant Proteins; Systemic Inflammatory Response Syndrome; COVID-19 Drug Treatment; 3. Good health; 03 medical and health sciences; Deoxyribonuclease I; Humans; Female; Aged

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.