The Use of Dornase Alfa in the Management of COVID-19-Associated Adult Respiratory Distress Syndrome

Abstract

Objective. Currently, management of acute respiratory distress syndrome (ARDS) in COVID-19 infection with invasive mechanical ventilation results in poor prognosis and high mortality rates. Interventions to reduce ventilatory requirements or preclude their needs should be evaluated in order to improve survival rates in critically ill patients. Formation of neutrophil extracellular traps (NETs) during the innate immune response could be a contributing factor to the pulmonary pathology. This study suggests the use of dornase alfa, a recombinant DNAse I that lyses NETs, to reduce ventilatory requirements and improve oxygenation status, as well as outcomes in critically ill patients with ARDS subsequent to confirmed or highly suspected COVID-19 infection. Design. A single-institution cohort study. Setting. Intensive care unit in a tertiary medical center. Patients. Adult patients with acute respiratory distress syndrome (ARDS) admitted to the ICU with confirmed COVID-19 infection. Intervention. Treatment with aerosolized dornase alfa. Measurements and Main Results. Of 39 patients evaluated, most patients had improvement in oxygenation measured by increase in the PaO2/FiO2 ratio, reduction in ventilatory support or other supportive oxygen requirements, and partial resolution of bilateral opacities visible on CXR, as well as improved outcome. Conclusions. Administration of inhalational dornase alfa via a filtered nebulizer medication system or through an adapter in a ventilator circuit should be considered in all COVID-19-positive patients with ARDS as early in the disease course as possible.

NETosis and the Immune System in COVID-19: Mechanisms and Potential Treatments

“…Weber et al showed efficacy of dornase alfa in a case series of five patients with COVID-19. Toma et al came to the same conclusion in a study of 39 COVID-19 patients (Weber et al, 2020;Toma et al, 2021).…”

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure

“…Currently, clinical data regarding the inhaled DNase in COVID-19 are very limited, coming only from two small, non-randomized, case-control trials enrolled ICU patients with ARDS [17,18]. Treatment with nebulized DNase in most of the patients was associated with improved oxygenation and outcome, especially when used earlier in the disease course [17,18]. Decreased NETs remnants in bronchoalveolar lavage fluid was also described [18].…”

“…Moreover, complement activation, triggering of the NF-κB and JAK/STAT pathways, have been described as partners in COVID-19 hyperinflammation [11][12][13]. Based on these mechanisms and the current ongoing randomized control trials (RCTs), immunomodulatory treatments including anakinra, a recombinant IL-1 receptor antagonist [14], tocilizumab, an anti-IL-6 receptor antagonist [15], baricitinib, a selective JAK-1/JAK-2 inhibitor [16] and nebulized recombinant human DNase [17,18] as an agent which dismantles the generated NETs, have been administered separately in patients with COVID-19-related SRF.…”

Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19

“…In another study, DNAse lessened ATP and ADP-induced thrombus formation in vivo, although it did not affect NET formation [169]. The DNAse inhibitor dornase alfa has recently gained attention towards COVID-19 treatment, with improvement in patient oxygenation being noted following its use in vitro and in vivo [170][171][172], while it remains to be explored whether these agents can influence clinical outcomes by halting platelet activation among other pathways. Chloramidine, a protein-arginine deiminase antagonist known for inhibiting NETosis, was also associated with reduced arterial thrombosis in vivo [173].…”