Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients
(2021) In Molecular and Cellular Proteomics 20.- Abstract
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. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting acute symptoms with clinically approved aerosolized Pulmozyme. No... (More)
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. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting 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 COVID-19 patients 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 haemorrhage, 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 rhDNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.
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- author
- Fisher, Jane LU ; Mohanty, Tirthankar LU ; Karlsson, Christofer LU ; Khademi, S M Hossein LU ; Malmström, Erik LU ; Frigyesi, Attila LU ; Nordenfelt, Pontus LU ; Malmstrom, Johan LU and Linder, Adam LU
- organization
-
- Translational Sepsis research (research group)
- Infection Medicine (BMC)
- Infection Medicine Proteomics (research group)
- Adaptive Immunity (research group)
- Intensive Care Epidemiology (research group)
- Anesthesiology and Intensive Care
- epIgG (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- Quantitative immunobiology (research group)
- BioMS (research group)
- Mass Spectrometry
- publishing date
- 2021-06-14
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular and Cellular Proteomics
- volume
- 20
- article number
- 100113
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:85111374552
- pmid:34139362
- ISSN
- 1535-9484
- DOI
- 10.1016/j.mcpro.2021.100113
- project
- COVID-19 proteome profiling reveals resolution of inflammatory pathways and respiratory distress after DNase treatment
- language
- English
- LU publication?
- yes
- id
- ca00e94a-b869-40f6-ac48-788e27439949
- date added to LUP
- 2021-07-02 06:40:10
- date last changed
- 2024-06-15 13:11:18
@article{ca00e94a-b869-40f6-ac48-788e27439949, abstract = {{<p>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. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting 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 COVID-19 patients 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 haemorrhage, 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 rhDNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.</p>}}, author = {{Fisher, Jane and Mohanty, Tirthankar and Karlsson, Christofer and Khademi, S M Hossein and Malmström, Erik and Frigyesi, Attila and Nordenfelt, Pontus and Malmstrom, Johan and Linder, Adam}}, issn = {{1535-9484}}, language = {{eng}}, month = {{06}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Molecular and Cellular Proteomics}}, title = {{Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients}}, url = {{http://dx.doi.org/10.1016/j.mcpro.2021.100113}}, doi = {{10.1016/j.mcpro.2021.100113}}, volume = {{20}}, year = {{2021}}, }