Pathogen effects on the brain: the case of SARS-CoV-2 spike protein and neuro COVID.

Many patients develop cognitive and neuropsychiatric issues after viral infections, but the mechanisms are not well understood. A case in point is Long-COVID syndrome, which may affect as many as 50 percent of patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by lingering physical and mental fatigue, brain fog and neuropsychiatric symptoms. Meanwhile, emerging evidence suggests the presence of inflammation around blood vessels in the brain due to the Spike protein remaining in "reservoirs" especially in the meninges that contain great numbers of the unique tissue immune cells, mast cells (MCs). In fact, Spike protein has been reported to stimulate MCs and microglia to release pro-inflammatory, neurotoxic and vasoactive mediators leading to Long-COVID and other neurodegenerative disorders. Thus, it is of great urgency to gain insight into how the Spike protein and neuroinflammatory molecules contribute to Long-COVID and how to regulate this response.