The SARS-CoV-2 spike protein is a long-lasting foreign pathogenic protein found in cells and tissues after COVID-19 respiratory illness and COVID-19 vaccination. The spike protein incites an inflammatory response and is a potent activator of nuclear factor kappa light chain enhancer of activated B cells (NF-κB). It can adversely impact any of the vital organs, such as the heart, lungs, brain, and kidneys, by inducing a severe autoimmune attack. The spike protein has been described as the causative factor for cardiovascular complications leading to increased mortality following mRNA injections. It can cause a cytokine storm that characterizes many cases of fatal COVID-19 respiratory illness. Additionally, it drives sustained inflammation in long COVID and vaccine injury syndromes in multiple tissues and organs and also by crossing the blood-brain barrier (BBB), where protective antibodies cannot act, thereby causing severe neuroinflammation through microglial activation and NFκB. It is therefore of utmost importance to repurpose drugs and introduce natural agents, in order to provide nontoxic therapies for spike protein injury syndromes, after COVID-19 illness, vaccination, and both exposures in combination. The systemic use of proteolytic naturally derived enzymes becomes of medical interest and could offer a safe and efficacious solution for the alleviation of both spike-protein-associated symptomatology and pathology.