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Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients

Fisher, Jane LU ; Mohanty, Tirthankar LU ; Karlsson, Christofer LU ; Khademi, S M Hossein LU ; Malmström, Erik LU ; Frigyesi, Attila LU ; Nordenfelt, Pontus LU orcid ; Malmstrom, Johan LU orcid and Linder, Adam LU (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
; ; ; ; ; ; ; and
organization
publishing date
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
  • pmid:34139362
  • scopus:85111374552
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}},
}