Acute lung injury, hypoxemia, and lethality in <i>hACE2</i>^fl/y and Shh^Cre/+; <i>hACE2</i>^fl/y mice after infection with SARS-CoV-2.

(A, B) Weight loss and survival of hACE2fl/y and ShhCre/+; hACE2fl/y mice after infection with 105 PFU of SARS-CoV-2. N = 8 (hACE2fl/y) and 7 (ShhCre/+; hACE2fl/y), two independent experiments. Note: Data for hACE2fl/y are the same as those shown in Fig 2D and 2E because ShhCre/+; hACE2fl/y animals were littermates of those animals. (C) Pulse oximetry measured in WT, hACE2fl/y, and ShhCre/+; hACE2fl/y mice at time of harvest 5–6 days after exposure to 105 PFU of SARS-CoV-2 virus. (D) HE staining of WT, hACE2fl/y, and ShhCre/+; hACE2fl/y lung tissue 6 days after exposure to 105 PFU of SARS-CoV-2 virus. Arrows, sites of bronchovascular immune cell infiltrate. Asterisks, intravascular thrombus. Representative of N = 3 animals per genotype. Scale bars 100 μm. Note: The hACE2fl/y data shown in panels A and B are the same as those shown in Fig 2, panels B-G. *p p p > 0.05 by unpaired two-tailed t test, one-way ANOVA with Holm–Sidak correction for multiple comparisons, or log-rank Mantel Cox test. These hACE2fl/y mice were littermates of the ShhCre/+; hACE2fl/y mice and contemporaneously infected. Numerical data in corresponding S1 Metadata tab. HE, hematoxylin–eosin; PFU, plaque-forming unit; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; WT, wild-type. (TIF)