Using GM-CSF as a Host Directed Therapeutic Against COVID-19
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
The coronavirus disease 2019 (COVID-19) has rapidly become a pandemic. COVID-19 poses a
mortality risk of 3-7%, rising to 20% in older patients with co-morbidities. Of all infected
patients, 15-20% will develop severe respiratory symptoms necessitating hospital admission.
Around 5% of patients will require invasive mechanical ventilation, and up to 50% will die.
Evidence in severe COVID-19 suggests that these patients experience cytokine storm and
progressed rapidly with acute respiratory distress syndrome and eventual multi-organ failure.
Early identification and immediate treatment of hyperinflammation is thus recommended to
reduce mortality. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) has been shown to
be a myelopoietic growth factor that has pleiotropic effects in promoting the differentiation
of immature precursors into polymorphonuclear neutrophils, monocytes/ macrophages and
dendritic cells, and also in controlling the function of fully mature myeloid cells. It plays
an important role in priming monocytes for production of proinflammatory cytokines under TLR
and NLR stimulation. It has a broad impact on the processes driving DC differentiation and
affects DC effector function at the mature state. Importantly, GM-CSF plays a critical role
in host defense and stimulating antiviral immunity. Detailed studies have also shown that
GM-CSF is necessary for the maturation of alveolar macrophages from foetal monocytes and the
maintenance of these cells in adulthood. The known toxicology, pharmacologic and safety data
also support the use of Leukine® in hypoxic respiratory failure and ARDS due to COVID-19.
This study aims to recruit patients with evidence of pneumonia and hypoxia who have increased
risk for severe disease and need for mechanical ventilation. The overall hypothesis is that
GM-CSF has antiviral immunity, can provide the stimulus to restore immune homeostasis in the
lung with acute lung injury from COVID-19, and can promote lung repair mechanisms, which
would lead to improvement in lung oxygenation parameters.