In the extreme opposite of the MA10/BALB model, the overwhelmed brain infection with Wuhan or WA-1 isolates of both K18- and AC70 hACE2-Tg mice, likely the main cause of mortality, similarly makes both classic ACE2-Tg mouse models less attractive for studying COVID-19 pathogenesis in humans. The gene discussed is ACE2; the disease is COVID-19.