Interestingly, anti-ACE2 IgM auto-antibodies have been shown to have no effect on ACE2 enzymatic activity, raising the possibility that anti-ACE2 IgM pentamers may mimic SARS-CoV-2 virion binding and membrane ACE2 release via ectodomain shedding (see Figure 1); an eventuality that could both maintain the systemic and deleterious ACE2 enzymatic activity even in the absence of viral load and provide a rationale for corticosteroid efficacy in COVID-19 [72]. The gene discussed is ACE2; the disease is COVID-19.