Fig. 4. Treatment with sACE22.v2.4-IgG1 mitigates lung vascular endothelial injury and ARDS induced by live SARS-CoV-2 infection and improves survival.
K18-hACE2 transgenic mice were inoculated with the SARS-CoV-2 isolate WA-1/2020 at 1 × 104 PFU. Group 1 received control PBS via intravenous injection 24 h postviral inoculation. Group 2 (v2.4 12 h) received sACE22.v2.4-IgG1 10 mg kg−1 via intravenous injection 12 h postinoculation and then daily subsequent injections at the same dose. Group 3 (v2.4 24 h) received sACE22.v2.4-IgG1 15 mg kg−1 via intravenous injection 24 h postinoculation and then daily subsequent injections at the same dose. a,b, Survival curves (a) and weights (b) for n = 10 mice for each group. c–e, Mouse lungs were obtained on day 7 postinoculation for assessment of lung vascular albumin permeability. c, Macroscopic images of lungs at baseline and day 7 postviral inoculation in three experimental groups without EBA (left) and with EBA injection (right). d, Quantification of EBA lung vascular endothelial permeability in all three experimental groups. e, Quantification of lung edema by wet/dry ratio in all three experimental groups at baseline and day 7 postinoculation. f,g, Time course of lung vascular endothelial permeability and edema formation of groups 2 (v2.4 12 h) (f) and 3 (v2.4 24 h) (g) as assessed by EBA assay and lung wet/dry ratio. Data are presented as the mean ± s.e.m. d,e, P values were calculated by two-way ANOVA with Tukey post hoc test. f,g, P values were calculated by one-way ANOVA with Tukey post hoc test.