SARS-Cov-2 infection as an ideal context for inducing autoantibodies to ACE2: Autoimmune clinical complications as possible causes for disease presentation, severity, and duration.

Abstract

A subset of patients affected by the recent Covid-19 pandemic develop critical or fatal clinical outcomes, which causes are not always fully understood. A delayed exaggerated immune and inflammatory response develops, inducing severe clinical complications which are associated with induced hemostasis activation, thrombosis, disseminated intra vascular coagulation, vasculitis, and multiorgan failure. This SARS-Cov-2 infection induces a dysregulation of the Renin Angiotensin Aldosterone system by shedding the protective cell surface receptor ACE2, and this can be a major contributor to disease evolution. In addition, the viral cell entry mechanism requires the formation of an intimate and high affinity binding complex between virus spike protein RBD and ACE2. An alloimmune response could then develop with generation of autoantibodies to ACE2, which could be responsible for an acute autoimmune response, and for the deleterious exacerbated inflammatory reaction. This report discusses the rationale for that hypothesis and describes how it could impact the disease course.