Understanding and treating the adverse effects of COVID-19 on the brain

A marked proportion of COVID-19 patients develop a spectrum of neurological symptoms ranging from acute, very severe outcomes like stroke, to longer term effects like headache, trouble thinking clearly, anxiety, and depression. Some of the more common symptoms like headache, trouble thinking clearly, anxiety, and depression (more common in women) can last long after the infection has cleared. These neurological symptoms are consistent with those seen when the body mounts a defense against an infection, in a process called inflammation. The body releases factors into the bloodstream called inflammatory mediators, and these can make their way into the brain. Once in the brain, these mediators trigger special brain immune and glial cells to become 'reactive'. In the reactive state, immune and glial cells start to dismantle and destroy neuronal connections, which can result in impaired decision-making, as well as anxiety and depression. This study will investigate how COVID-19-associated inflammation in the body leads to changes in the brain, specifically changes in these immune and glial cells, as well as in neuronal connections - and will also test a drug to prevent or reverse these changes. This drug blocks the function of a protein that normally regulates neuronal connections and immune and glial cell responses, and is already approved for use in humans. To do this work, we will use our skillset in microscopy and biochemistry, and will capitalize on our expertise in neuroinflammation and immune and glial cell biology, as well as our understanding of the regulation of neuronal connection structures. The outcomes of this work will provide critical new insight into brain changes resulting from COVID-19, which will inform diagnosis and treatment. Moreover, we will directly test the effects of an approved drug, and this could lead to clinical trials for repurposing this drug to treat COVID-19, thereby opening up new avenues for therapeutic intervention.