Consideration of dornase alfa for the treatment of severe COVID-19 acute respiratory distress syndrome
A P Earhart, Z M Holliday, H V Hofmann, A G Schrum, A P Earhart, Z M Holliday, H V Hofmann, A G Schrum
Abstract
We propose a likely contribution to severe COVID-19 morbidity by extracellular DNA in neutrophil extracellular traps (NETs). Dornase alfa degrades extracellular DNA to reduce mucus rigidity and accumulation, and was associated with respiratory improvement in a first patient. Dornase alfa should be considered for clinical trials in treatment of severe COVID-19.
Keywords: COVID-19; DNAse 1; Neutrophil extracellular trap; acute respiratory distress syndrome; dornase alfa.
© 2020 The Author(s).
Figures
Model of how dornase alfa-sensitive neutrophil extracellular traps (NETs) from neutrophils may reinforce mucus accumulation, rigidity and airway occlusion in severe coronavirus disease 2019 (COVID-19). (a) Viral infection causes inflammation and respiratory distress (darkened lungs). Lung-infiltrating neutrophils produce NETs whose large quantities of chromosomal, extracellular DNA are susceptible to degradation by dornase alfa (recombinant human deoxyribonuclease I, right). (b) Close up view of alveoli. Without dornase alfa treatment (left), NETs reinforce the accumulation and rigidity of mucus that can increase lung injury and reduce oxygenation. Dornase alfa treatment (right) reduces NET-mediated reinforcement of mucus, making it less rigid (lighter yellow) and facilitating mucus clearance, so reducing lung injury and increasing gas exchange. (c) The rate at which recovery from severe COVID-19 occurs naturally (left, thin arrow) might be increased by dornase alfa treatment (right, thicker arrow). Figure was created with BioRender.
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Source: PubMed