COVID-19-A Theory of Autoimmunity Against ACE-2 Explained

Abstract

The COVID-19 pandemic caused by the coronavirus SARS-COV-2 has cost many lives worldwide. In dealing with affected patients, the physician is faced with a very unusual pattern of organ damage that is not easily explained on the basis of prior knowledge of viral-induced pathogenesis. It is established that the main receptor for viral entry into tissues is the protein angiotensin-converting enzyme-2 ["ACE-2", (1)]. In a recent publication (2), a theory of autoimmunity against ACE-2, and/or against the ACE-2/SARS-COV-2 spike protein complex or degradation products thereof, was proposed as a possible explanation for the unusual pattern of organ damage seen in COVID-19. In the light of more recent information, this manuscript expands on the earlier proposed theory and offers additional, testable hypotheses that could explain both the pattern and timeline of organ dysfunction most often observed in COVID-19.

Keywords: COVID-19; autoimmunity; lung; macrophage; solubleACE-2.

Figure 1

Surface Plasmon Resonance (SPR) determination of soluble ACE-2 binding affinity to SARS-CoV-2 spike protein. (A) Recombinant human ACE-2 (rhACE-2, Acrobiosystems), was analyzed by SPR assay for binding to a recombinant SARS-CoV-2 spike protein receptor binding domain (RBD, Acrobiosystems) immobilized in the flow chamber. As shown, increasing concentrations of the soluble rhACE-2 (in nM) showed proportional increases in binding to immobilized spike protein RBD. (B) These data allowed estimation of kD ~74 nM.

Figure 2

In a bead-based assay system [AlphaLISA proximity assay, (32)], which uses both rhACE-2 and spike RBD immobilized to beads, soluble rhACE-2 added to the assay buffer showed concentration-dependent inhibition of bead-bound spike RBD binding to bead-bound rhACE-2, with an IC50 ~2.4 nM.