Recruiting the innate immune system with GM-CSF to fight viral diseases, including West Nile Virus encephalitis and COVID-19

Abstract

<ns4:p>As the coronavirus disease 2019 (COVID-19) pandemic grows throughout the world, it is imperative that all approaches to ameliorating its effects be investigated, including repurposing drugs that show promise in other diseases. We have been investigating an approach to multiple disorders that involves recruiting the innate immune system to aid the body’s healing and regenerative mechanism(s). In the case of West Nile Virus encephalitis and potentially COVID-19, the proposed intervention to stimulate the innate immune system may give the adaptive immune response the necessary time to develop, finish clearing the virus, and provide future immunity. Furthermore, we have found that GM-CSF-induced recruitment of the innate immune system is also able to reverse brain pathology, neuroinflammation and cognitive deficits in mouse models of Alzheimer’s disease and Down syndrome, as well as improving cognition in normal aging and in human patients with cognitive deficits due to chemotherapy, both of which exhibit neuroinflammation. Others have shown that GM-CSF is an effective treatment for both bacterial and viral pneumonias, and their associated inflammation, in animals and that it has successfully treated pneumonia-associated Acute Respiratory Distress Syndrome in humans. These and other data strongly suggest that GM-CSF may be an effective treatment for many viral infections, including COVID-19.</ns4:p>

African Swine Fever Virus Infection and Cytokine Response In Vivo: An Update

“…GM-CSF induces recruitment of cells belonging the innate immune system. Different studies have also suggested that this cytokine could be used as an effective treatment for encephalitis caused by West Nile virus, diverse bacterial infections and viral pneumonia [ 116 ].…”

Modulation of immune responses in the central nervous system by Zika virus, West Nile virus, and dengue virus

“…Additionally, chemokines are induced to recruit immune cells, including macrophages and lymphocytes, to the site of infection, aiding in viral clearance and tissue repair. One of the critical challenges in WNV infection lies in the virus's ability to antagonise these immune responses through the action of its non‐structural proteins 22 . WNV's NS5 has been shown to inhibit IFN signalling by targeting STAT1 phosphorylation, thereby dampening the antiviral state within infected cells.…”

Recent advances in antibody‐based immunotherapy strategies for COVID‐19

“…Thereby, GM‐CSF has now been proposed as a possible target for COVID‐19, and its mAb administration has been demonstrated to cause therapeutic effects in patients. 150 , 151 …”