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Good day to all, I’m Yu Hong, presenting my part of mechanism of COVID-19 by Neuroinvasion leading to Neurodegeneration. Here’s a summary of Neuroinvasion of SARS-CoV-2 in human and mouse brain, but we’ll just discuss about what happens in human brain organoids and observe some post-mortem brain tissue samples of COVID patients. Now, our focus here is the pathway neuroinvasion activating glial cells and further leading to neurodegenerative diseases. The first line of defence for SARS-CoV-2 neuroinvasion is the activation of microglia. So, we have to take note that the activation of microglia happens after all these pathways of neuroinvasion into the PNS and CNS. Microglia are the residing mononuclear phagocytes of the brain, highly heterogeneous cells within the healthy CNS. The presence of activated glial cells is considered a marker of brain injury and neuroinflammation. However, neuroinflammation mediates a secondary damage by secreting cytokines, neurotrophic factors, and activation of proteases. Microglia is not only responsible for immune mediated responses in the brain but can respond rapidly to environmental changes, with an increasing evidence showing that brain resident glial cells can be transformed into an aggressive effector cells causing neuronal damage. Therefore, microglia may confer short-term neuroprotection or trigger long-term neurodegeneration depending on the interplay between pro- and anti-inflammatory cytokines released in response to viral infection. Now, we explore how all these events would then lead to neurodegeneration. From the previous slide, we know that activated microglia are the main contributors to release cytokine and chemokine. But these neuronal cells also express specific molecules similar to immune receptors to modulate the innate/inborn/natural immune response in the brain. These molecules contribute to the neuroplasticity and organisation of neuronal networks and synapses. The autonomous activation of neuronal cells using the innate receptors during COVID infections compromises neuroplasticity and triggers neuronal dysfunction. Furthermore, viral infection-induced inflammatory events show similarities to early neurodegenerative conditions, including altered expression of proteins used in axonal transport and synaptic transmission. Dendritic spines are targeted, and synaptic degeneration occurs. Synaptic dysfunction occurs typically in the early stages of Alzheimer’s disease pathogenesis. And here are some journals cited. Thank you. So, it’s me again, presenting a part relevant real-life examples of COVID-19. For this part, we’re going to look into some latest observations in post-mortem brains tissues of COVID-19 patients, as this is kind of related to what we’ve learnt in the practical histology sessions. SARS-CoV-2 causes significant neuronal death in human brain organoids. Using electron microscopy, viral particles were identified budding from the ER, indicating the virus’s replication ability using the neuron cell machinery. Diverging metabolic changes is also found in infected versus neighbouring cells, suggesting that the infected cells can cause local changes to their microenvironment, affecting survival of nearby cells. The presence of acute hypoxic ischemic damage and microinfarcts in post-mortem brain samples of COVID-19 patients is also observed, which then causes brain vasculature disturbance. In conclusion, SARS-CoV-2 can infect cortical neurons in brain organoids, promote neighbouring cell death and is detected in neurons and microvasculature of COVID-19 post-mortem tissues samples. These provide evidence of direct neurotropic capability of SARS-CoV-2. So, here is a diagram of recent observations made, proving the neurotropic capability of SARS-CoV-2 in ischemic regions and cortical neurons of human brain organoids. And here is an article cited. Thank you.