COVID-19 is without question a multi-systemic syndrome like no other with vast variance and involvement. I believe we are viewing the disease incorrectly. COVID-19 is unique. Instead of the DISEASE causing PATHOLOGY, the DISEASE dysregulates TRANSCRIPTION causing the HOST to cause PATHOLOGY.
It is the only logical conclusion I can arrive at given the unprecedented panoply of systemic involvement and symptoms, and how UNIQUE it ultimately is, to each host.
Many different diseases and syndromes, including cancer, autoimmunity, neurological disorders, diabetes, cardiovascular disease, and obesity, can be caused by mutations in regulatory sequences and in the transcription factors, cofactors, chromatin regulators, and noncoding RNAs that interact with these regions.
What is most interesting is that it is now understood that a small fraction of the hundreds of transcription factors that are present dominate the control of much of the active gene expression program.
The Spike Protein not only binds to Ace-2, but it also, like a droid, "hacks" its vast transcription network.
A transcription regulatory network within the ACE2 locus may promote a pro-viral environment for SARS-CoV-2 by modulating expression of host factors.