PhD defence: Beneath the surface - Innate immune responses and brain pathology following SARS-CoV-2 infection

PLEASE NOTE: The candidate gives a layman's talk, therefore the livestream will start fifteen minutes earlier.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as a respiratory virus and rapidly led to a global pandemic. SARS-CoV-2 infection can trigger COVID-19 with highly variable clinical outcomes, and a substantial number of patients continue to experience symptoms for months afterward. This condition is known as long COVID or PASC, which frequently includes neurological and neuropsychiatric complaints. While neuropathological changes such as vascular damage, neuroinflammation, and neuronal injury have been documented in severe or fatal COVID-19 cases, far less is known about the brain consequences of mild infection, or how these changes evolve over time. This thesis used a non-human primate model to longitudinally track SARS-CoV-2-associated neuropathology and protein changes in blood and cerebrospinal fluid following mild Delta variant infection, and to examine possible links to neurodegenerative diseases.

Brain imaging and postmortem tissue analysis revealed sustained immune activation in the hippocampus and pons for weeks after infection. In the substantia nigra, the region most affected in Parkinson's disease, infection led to dopaminergic neuron loss and prolonged innate immune activity, accompanied by elevated levels of neurofilament light chain, a marker of neuronal damage, in both blood and cerebrospinal fluid (CSF). Proteomic analysis conducted seven weeks post-infection identified alterations in inflammatory, synaptic, and neurodegeneration-related proteins, including reduced amyloid-related proteins in CSF, showing some overlap with patterns reported in Alzheimer's disease. These protein changes were consistent with gene expression data from brain tissue.

Together, these findings show that even mild SARS-CoV-2 infection can cause lasting neuroinflammation, neuronal injury, and protein changes resembling those in neurodegenerative disorders, highlighting the need for further translational and longitudinal research into virus-related neurological risk.