Project 466910

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has taken a major toll on human life. There has been emergent evidence of brain-related symptoms such as depression, anxiety and brain fog months after the infection has been cleared. This condition has been termed ;post-acute sequalae of COVID-19 (PASC), although the origin of these symptoms is unknown. Research suggests SARS-CoV-2 can migrate to the brain and invade neurons, the brains functional cells, and microglia, the brain-resident immune cells that attack harmful substances like viruses. Some of the mechanisms by which SARS-CoV-2 damage the brain overlap with neurodegenerative diseases like Alzheimers. Specifically, inflammation is crucial for clearing infection, but when sustained for long periods of time, accumulation can result in overactive microglia that damage brain tissue. I suspect that microglia are the primary cause of long-term perturbations in brain health in recovered COVID-19 patients suffering from PASC. I will study PASC using miniature, simplified brains in a dish (known as cerebral organoids) derived from stem cells given specific instructions to form brain tissue. Stem cells function like embryonic cells and can form most bodily tissues depending on their nutritional environment. Once formed, I will infect cerebral organoids with SARS-CoV-2 and other related viruses to determine their effects on brain cell function. Signals triggering inflammation, cell death, and neurodegeneration will be traced back to microglial interactions with neurons and supporting nerve cells. These experiments will characterize the poorly understood post-infection environment of the brain and buttress our understanding of PASC to inform better treatment options for patients recovering from COVID-19.