SARS-CoV-2 Spike Protein in the Skull-Meninges-Brain Axis

COVID-19 has been associated with a variety of neurological symptoms, including brain fog and brain tissue loss. This raises concerns about the virus's acute and potential chronic impacts on the brain. Using whole mouse and human tissue clearing, we determined all potential tissues targeted by the SARS-CoV-2 and showed that the spike protein accumulates in the skull-meninges-brain axis in both mice and humans. Injection of the spike protein into the mouse skull alone was sufficient to cause cell death in the brain. Notably, we found spike protein in the skull of ~60% of deceased people who had COVID-19 in the past. Mass spectrometry-based proteomics in mice and humans revealed dysregulated inflammatory and vascular pathways throughout tissues in the skull-meninges-brain axis. Overall, SARS-CoV-2 spike protein accumulation in the CNS borders might be involved in the immediate and long-term consequences in the brain parenchyma, and this may present diagnostic and therapeutic opportunities.