Autoimmunity to ACE2 as a possible cause of tissue inflammation in Covid-19

The delayed lung damage after SARS-CoV-2 infection may be caused by an autoimmune response to ACE2 induced by forced presentation of the ACE2 protein in a complex with CoV Spike in Fc Receptor positive Antigen Presenting Cells in the lung. The likelihood that this hypothesis is valid is low, but it is easily tested.

1) Autoantibodies and T cells to ACE2 may be found in patients with the lung damage but not in those without 2) There may be an HLA linkage with the delayed lung disease 3) Vaccines based on the spike protein might initiate the process by amplifying Fc mediated uptake of ACE2-Spike complexes into APCs.

The development of autoantibodies to ACE2 might predict the development of the inflammatory phase of Covid-19 disease. It might be wise to consider engineering versions of the spike that no longer bind to ACE2 for inclusion in vaccines.