Aerosolized dornase alfa (DNase I) for the treatment of severe respiratory failure in COVID-19: a randomized controlled trial
Per Åkesson, Lisa Mellhammar, Magnus Rasmussen, Malin Inghammar, Sara Jesperson, Fredrik Månsson, Elin Economou Lundeberg, John Walles, Martin Wallberg, Attila Frigyesi, M.D Adam Linder
Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf246
Background: The 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 five days or a placebo in addition to standard-of-care. The primary outcome was discharge from the hospital or an oxygen saturation of >93% without respiratory support.
Conflict of interests: None
Author contributions PÅ helped initiate the study, enrolled patients and wrote the manuscript LM helped initiate the study, enrolled patients and critically revised the manuscript MR wrote the application for ethical permit and critically revised the manuscript MI helped iniate the study, enrolled patients and critically revised the manuscript SJ made the statistical analysis FM included patients in Malmö and critically revised the manuscript
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doi:10.1186/s10020-020-00215-wDOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>The 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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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 five days or a placebo in addition to standard-of-care. The primary outcome was discharge from the hospital or an oxygen saturation of &gt;93% without respiratory support.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>A total of 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 or placebo. Secondary outcomes such as mortality, a new episode of hypoxia, length of stay in the hospital, and adverse events were similar across groups. A subanalysis of patients older or younger than 65 showed no differences in primary or secondary outcomes.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>",
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