There is emerging evidence that SARS-CoV2 or COVID19 gains entry into human brain cells leading to a sequela of neurologic symptoms. There is concern that SARS-CoV2 may lead to neurotoxicity and that neuronal death in the regions of the brain that control respiration and cardiac function may be a contributing factor to the acute loss of cardio respiratory function and death. SARS-CoV2 could gain access to the brain by several routes including through the nose, or neurons innervating infected lung tissue or through the cells lining blood capillaries in the brain. COVID-19 patients lose their sense of smell or taste often before the onset of respiratory symptoms and a patient presented with Guillain-Barr syndrome before testing positive for SARS- CoV2. It appears that at least 36% of COVID19 patients had neurologic manifestations including headache, nausea, loss of consciousness, strokes, confusion, encephalitis, meningitis and seizures. These clinical observations strongly indicate a role for SARS-CoV2 in the death of neurons and importantly the brain may be one of the first tissues infected and affected. The actions of SARS-CoV2 on the different cells in the brain, as well as the infectivity, tropism, and replication in brain cells is not yet known. In this application we propose to evaluate: (1) The tropism and replication of SARS-CoV2 in human microglia, astrocytes, neurons, and determine relative susceptibility? (2) The mechanisms of cellular injury and evaluate potential protective approaches. (3) Determine the transcriptional responses to SARS CoV2 infection in human neurons, astrocytes, and microglia at the single cell level to gain new insight into the differential response of brain cells to SARS CoV2 to better understand the neural deficits the virus causes.
There is growing evidence that SARS CoV2, the virus that causes COVID19, targets the brain resulting in a range of neurological symptoms and it may contribute to cardiopulmonary collapse. There is the possibility that the virus may stimulate events that lead to advanced misfolding of proteins such as alpha-synuclein, amyloid beta and tau. Additionally, neural cultures from patient derived iPSCs maybe more susceptible to the actions of SARS CoV2. The project objectives are to understanding the actions of SAR CoV2 on neurologic function to help guide the treatment and management of patients.
