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Clinical Trial
. 2020 Sep 29;26(1):91.
doi: 10.1186/s10020-020-00215-w.

Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series

Andrew G Weber  1 , Alice S Chau  2 , Mikala Egeblad  3 , Betsy J Barnes  4 , Tobias Janowitz  5   6
Affiliations
Free PMC article
Clinical Trial

Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series

Andrew G Weber et al. Mol Med. .
Free PMC article

Abstract

Background: Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system.

Methods: Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed.

Results: The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified.

Conclusions: Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.

Keywords: ARDS; COVID-19; Coronavirus; Dornase alfa; Mucopurulent secretions; Neutrophil extracellular traps; SARS-CoV-2; VV-ECMO.

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Conflict of interest statement

Mikala Egeblad is receiving lonodelestat from Santhera for preclinical studies, but has no financial relationship with Santhera. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the clinical course of five patients treated with nebulized dornase alfa + albuterol (nDA + A)
Fig. 2
Fig. 2
Patient-level data of respiratory function during treatment with nebulized dornase alfa + albuterol (nDA + A). Values were extracted from the medical records the day before and up to the seven days after the initiation of treatment. Values are graphed in black for patients after they ceased nDA + A treatment. Dashed lines indicate patients on VV-ECMO. Not all markers were measured daily for every patient. FiO2: fraction of inspired oxygen; PaCO2: partial pressure of carbon dioxide
Fig. 3
Fig. 3
Patient-level data of systemic disease during treatment with nebulized dornase alfa + albuterol (nDA + A). Values were extracted from the medical records the day before and up to the seven days after the initiation of treatment. Values are graphed in black for patients after they ceased nDA + A treatment. Dashed lines indicate patients on VV-ECMO. Not all markers were measured daily for every patient. CRP: C-reactive protein; LDH: lactate dehydrogenase
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