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Aerosolized Dornase Alfa (DNase I) for the Treatment of Severe Respiratory Failure in COVID-19 : A Randomized Controlled Trial

Åkesson, Per LU ; Mellhammar, Lisa LU ; Rasmussen, Magnus LU orcid ; Inghammar, Malin LU ; Jesperson, Sara ; Månsson, Fredrik LU ; Economou Lundeberg, Elin ; Walles, John LU orcid ; Wallberg, Martin LU and Frigyesi, Attila LU , et al. (2025) In Open Forum Infectious Diseases 12(5).
Abstract

Background: Lung injury in COVID-19 is characterized by neutrophil invasion and the release of neutrophil extracellular traps (NETs). An aberrant NET formation may induce local inflammation and increase sputum viscosity. Inhalation of DNase I (dornase alfa) is a treatment option that degrades NETs in the airways. Previous case series have indicated positive clinical effects of inhaled dornase alfa. Methods: Patients admitted to the hospital with acute COVID-19 and hypoxia (oxygen saturation <90%) were randomly assigned to receive aerosolized dornase alfa twice daily for 5 days or a placebo in addition to standard of care. The primary outcome was discharge from the hospital or an oxygen saturation >93% without respiratory support.... (More)

Background: Lung injury in COVID-19 is characterized by neutrophil invasion and the release of neutrophil extracellular traps (NETs). An aberrant NET formation may induce local inflammation and increase sputum viscosity. Inhalation of DNase I (dornase alfa) is a treatment option that degrades NETs in the airways. Previous case series have indicated positive clinical effects of inhaled dornase alfa. Methods: Patients admitted to the hospital with acute COVID-19 and hypoxia (oxygen saturation <90%) were randomly assigned to receive aerosolized dornase alfa twice daily for 5 days or a placebo in addition to standard of care. The primary outcome was discharge from the hospital or an oxygen saturation >93% without respiratory support. Results: In total, 76 patients were randomized. The study was stopped when the Omicron virus variant appeared. The clinical response rate did not differ between patients receiving the active substance and placebo. Secondary outcomes were similar across groups, such as mortality, a new episode of hypoxia, length of stay in the hospital, and adverse events. A subanalysis of patients older or younger than 65 years showed no differences in primary or secondary outcomes. Conclusions: Aerosolized dornase alfa failed to improve hypoxia in hospitalized patients with acute COVID-19. The study was conducted during a time of heterogeneity in viral variants and vaccination status of participants. Whether dornase alfa affects the outcomes in other respiratory infections requires further study.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aerosolized DNase I, COVID-19, NETs, respiratory failure, sepsis
in
Open Forum Infectious Diseases
volume
12
issue
5
article number
ofaf246
publisher
Oxford University Press
external identifiers
  • scopus:105005189885
  • pmid:40365079
ISSN
2328-8957
DOI
10.1093/ofid/ofaf246
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of Americ.
id
e616f9f0-abe3-4989-9b1f-902957f619c0
date added to LUP
2025-08-05 14:02:49
date last changed
2025-08-19 15:18:23
@article{e616f9f0-abe3-4989-9b1f-902957f619c0,
  abstract     = {{<p>Background: Lung injury in COVID-19 is characterized by neutrophil invasion and the release of neutrophil extracellular traps (NETs). An aberrant NET formation may induce local inflammation and increase sputum viscosity. Inhalation of DNase I (dornase alfa) is a treatment option that degrades NETs in the airways. Previous case series have indicated positive clinical effects of inhaled dornase alfa. Methods: Patients admitted to the hospital with acute COVID-19 and hypoxia (oxygen saturation &lt;90%) were randomly assigned to receive aerosolized dornase alfa twice daily for 5 days or a placebo in addition to standard of care. The primary outcome was discharge from the hospital or an oxygen saturation &gt;93% without respiratory support. Results: In total, 76 patients were randomized. The study was stopped when the Omicron virus variant appeared. The clinical response rate did not differ between patients receiving the active substance and placebo. Secondary outcomes were similar across groups, such as mortality, a new episode of hypoxia, length of stay in the hospital, and adverse events. A subanalysis of patients older or younger than 65 years showed no differences in primary or secondary outcomes. Conclusions: Aerosolized dornase alfa failed to improve hypoxia in hospitalized patients with acute COVID-19. The study was conducted during a time of heterogeneity in viral variants and vaccination status of participants. Whether dornase alfa affects the outcomes in other respiratory infections requires further study.</p>}},
  author       = {{Åkesson, Per and Mellhammar, Lisa and Rasmussen, Magnus and Inghammar, Malin and Jesperson, Sara and Månsson, Fredrik and Economou Lundeberg, Elin and Walles, John and Wallberg, Martin and Frigyesi, Attila and Linder, Adam}},
  issn         = {{2328-8957}},
  keywords     = {{aerosolized DNase I; COVID-19; NETs; respiratory failure; sepsis}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  publisher    = {{Oxford University Press}},
  series       = {{Open Forum Infectious Diseases}},
  title        = {{Aerosolized Dornase Alfa (DNase I) for the Treatment of Severe Respiratory Failure in COVID-19 : A Randomized Controlled Trial}},
  url          = {{http://dx.doi.org/10.1093/ofid/ofaf246}},
  doi          = {{10.1093/ofid/ofaf246}},
  volume       = {{12}},
  year         = {{2025}},
}