Aerosolized Dornase Alfa (DNase I) for the Treatment of Severe Respiratory Failure in COVID-19 : A Randomized Controlled Trial
(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.
(Less)
- author
- organization
- publishing date
- 2025-05-01
- 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
-
- pmid:40365079
- scopus:105005189885
- 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
- 2025-08-06 03:00:08
@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 <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.</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}}, }