The three groups of K18 hACE2 transgenic mice were inoculated by SARS-CoV-2 variant P.1 (Brazil) at 1×104 PFU. Group 1 (PBS): PBS was given by IV injection 24 hours post inoculation. Group 2 (V2.4 12H): sACE22.v2.4-IgG1 10mg/kg were given by IV injection 12 hours post inoculation. Group 3 (V2.4 24H): sACE22.v2.4-IgG1 15mg/kg were given by IV injection 24 hours post inoculation. The mice were injected once per day for 7 days. The survival probability was observed (A) and mouse weights were measured (B). N=10 for each group. (C-D) The mouse lungs were harvested at Day 6 post-inoculation to evaluate lung transvascular permeability – EBA assay (C) and lung wet/dry ratio (D) with baseline mouse lungs as control. (E) The viral loads of SARS-CoV-2 in the lungs harvested at baseline and Day 6 post-inoculation of SARS-CoV-2 variant P.1 (Brazil) were measured by real-time quantitative PCR for the mRNA expression level of SARS-CoV-2 Spike and SARS-CoV-2 NSPs. (F) Viral Plague Form Assay was performed to measure the viral loads of SARS-CoV-2 in the lungs harvested at baseline and Day 6 post-inoculation of SARS-CoV-2 variant P.1 (Brazil). (G-H) Time course of lung transvascular permeability of V2.4 12H treatment group. The EBA assay (G) and Wet/dry ratio (H) were measured at baseline, Day 6 and Day 14 post-inoculation. (I) Representative H&E staining of lung sections at baseline (1st column), control PBS group at day 7 post-inoculation with the P.1 variant (2nd column), sACE2.V2.4-IgG 12H treatment group at day 7 (3rd column), and sACE2.V2.4-IgG 24H treatment group at day 7 (4th column) post-inoculation with the P.1 variant. The images in the first row are low magnifications. Highlighted areas (Red) are shown in higher magnification in the second row. N=4 for C, D, E, F, G, and H. Data are presented by mean ± SEM. *: P<0.05, **: P<0.01, ***: P<0.001, ****: P<0.0001 by Two-way ANOVA for C & D; one-way ANOVA for E, F, G & H.