ACE2 and infection: In contrast, the K18-ACE2 transgenic mouse has no infection of the conducting airways but develops significant pulmonary disease, more analogous to that reported in human patients with severe clinical COVID-19; however, the lethality attributed to neuro-invasion including involvement of the respiratory center of the brain confounds the value of the K18-ACE2 transgenic mouse model for understanding transmission, pulmonary pathophysiology during late states of disease, and efficacy of T cell responses to vaccination and therapeutics block viral entry into permissive cells.