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

Townsend, Alain

HYPOTHESIS: 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. TESTABLE PREDICTIONS: 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. PRACTICAL IMPLICATIONS: 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. BACKGROUND: Infection by SARS-CoV-2 is followed by an inflammatory pneumonia in ∼14% of cases [1] and widespread organ damage [2]. The risk increases with age and certain predisposing conditions. Of these, hypertension stands out with 6.3% risk of death [3]. The virus enters cells by binding to the ACE2 protein [4]. ACE2 expression may be increased in hypertension, and this could be the basis for the predisposition by enhancing uptake of virus into cells that express ACE2 in lung, heart, blood vessels and kidney [5].