A Woman With Fever, Confusion, and Seizures

A 62-year-old woman sought care in late summer for a 4-day history of upper respiratory tract symptoms, intermittent fevers, headache, and a 1-day history of disorientation, word-finding difficulties, and unsteady gait. Upon arrival to the emergency department, she had a witnessed seizure and was intubated because of increased lethargy. Her temperature was 39.4 °C, but she was otherwise hemodynamically stable. She had normal ophthalmoscopic examination findings and antigravity strength in all 4 extremities. Her deep tendon reflexes were brisk, but plantar responses were flexor. She had no rash. Cerebrospinal fluid analysis showed a normal glucose value, protein concentration of 82 mg/dL, and mixed pleocytosis. She had been hiking recently, but her family reported that there were no tick exposures or mosquito bites. Brain magnetic resonance imaging showed areas of T2 fluid-attenuated inversion recovery hyperintensity involving primarily the left thalamus and basal ganglia without definitive gadolinium enhancement. Both serum and cerebrospinal fluid were positive for immunoglobulin M antibodies to West Nile virus. The patient was diagnosed with West Nile virus encephalitis. After the seizure, the patient was treated with levetiracetam, and empiric antimicrobials were started for acute meningoencephalitis, along with adjunctive dexamethasone. Continuous electroencephalography was obtained because of the persistent encephalopathy and showed no evidence of subclinical seizures. The dexamethasone was stopped after 2 doses because of low suspicion for pneumococcal meningitis, and the antibiotics were discontinued after results of serum and cerebrospinal fluid cultures were negative for bacteria (48 hours). Acyclovir was stopped after the polymerase chain reaction results were negative for herpes simplex virus and varicella-zoster virus.

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

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.