COVID-19 proteome profiling reveals resolution of inflammatory pathways and respiratory distress after DNase treatment

Severe COVID-19 can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hall mark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe COVID-19 patients reveal high levels of neutrophil extracellular trap(s) (NETs) components, which was confirmed by microscopy. Degrading pulmonary NETs using clinically approved aerosolized recombinant human DNase (rhDNase/Pulmozyme) improved pulmonary function, reversed hypoxemia, and aided in the rapid recovery of severely ill COVID-19 patients. 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 local reduction of haemorrhage, plasma leakage and inflammation in the airways, and a reversion of the systemic inflammatory state in the blood plasma. Taken together, the results show that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high flow oxygen therapy. Targeting NETs may have significant therapeutic implications in COVID-19 disease and warrants further studies.