Sun, S. et al. Nat Commun. 12, 5654 (2021)

SARS-CoV-2, which relies on cellular receptor angiotensin-converting enzyme 2 (ACE2) to enter host cells, cannot infect standard laboratory mice due to differences in amino acid residues between mouse and human ACE2. In Nature Communications, Sun et al. report the generation of a lethal mouse-adapted SARS-CoV-2 for studying COVID-19 pathogenesis in mice.

Varying doses of mouse-adapted SARS-CoV-2 strain MASCp36 — a strain generated by further passaging of previously described MASCp6 — were intranasally inoculated in young, old female and male mice. In infected mice, MASCp36 caused severe respiratory symptoms, massive macrophages and neutrophils infiltration, high levels of proinflammatory cytokines, as well age- and gender-specific responses, resembling the clinical manifestations of severe COVID-19 in humans.