Human prion protein and prion-like protein misfolding are widely recognized as playing a causal role in a large and growing number of neurodegenerative diseases. Here we summarize the compelling evidence that the spike protein of SARS-CoV-2 contains extended amino acid sequences previously established as characteristic of a prion-like protein. This suggests that vaccine-induced spike protein production is synonymous with production of a prion-like protein, and we trace some of the various pathways through which these proteins should be expected to traverse and distribute throughout the body. We describe some of the highly concerning biological consequences that would be expected to occur with increased frequency as a consequence. Specifically, we describe spike-protein contribution, via its prion-like properties, to neuroinflammation and neurodegenera-tive diseases; to clotting disorders within the vasculature; to suppressed prion protein regulation in the context of widely prevalent insulin resistance; and other health complications it could be expected to induce. We explain why these prion-like characteristics are more relevant to vaccine-related mRNA-induced spike proteins than natural infection with SARS-CoV-2. We conclude with some potentially ominous public health implications and recommendations for investigations of these possibilities.