Fig. 3: SARS-CoV-2 S and SARS-CoV-2 infection triggers vascular leak in vivo.

A A representative mouse back from a dermal leak experiment. The dorsal dermises of mice were injected intradermally with the treatments and doses indicated. Mice then received a dextran-680 tracer molecule intravenously. Mouse dermises were collected 2 h post-treatment, and quantification of local dermal leak was assessed by a fluorescent scanner. B Quantification of A from mice treated with PBS (n = 27), DENV2 NS1 (15 µg; n = 5), S (10 µg; n = 25), and S (25 µg; n = 5). C Representative lung images from a SARS-CoV-2 S systemic vascular leak assay. Mice were administered 50 µg of SARS-CoV-2 S or ovalbumin intranasally as indicated, and 22 hpt were administered a dextran-680 tracer intravenously as in A. Organs of mice were collected 2 hours post dextran-680 administration (24 hours post-S treatment), and accumulation of dextran-680 was measured with a fluorescent scanner. D Quantification of C from n = 6 mice. E Same as C except representative images of spleens are shown. F Quantification of E from n = 6 mice. G Same as C except representative images of small intestine are shown. H Quantification of G from n = 5 mice. I, J Hematoxylin and eosin (H&E) staining was performed on lung sections from K18-hACE2 mice 7 days post-infection with 100 TCID₅₀ units of SARS-CoV-2 WA/1 isolate. Displayed are representative images of lungs from n = 3 mice in mock-infected conditions (I) and from n = 4 mice infected with SARS-CoV-2 (J); left panels with scale bars at 2 mm and right panels consisting of zoomed-in insets with scale bars at 100 µm. Arrows point to dispersed red blood cells. K Representative lung images from C57BL/6 mice infected with the indicated dose of SARS-CoV-2 mouse-adapted strain (MA-10) for 7 days. Mice were administered a dextran-680 tracer intravenously as in A. Lungs were collected 2 hours after dextran-680 administration and fixed overnight in formalin, and the fluorescence accumulation was measured with a fluorescent scanner. L Quantification of K from n = 5 mice, except for the 2 × 10⁴ PFU condition, which was from n = 4 mice. MFI is mean fluorescence intensity. All data are plotted as mean + /− SEM with *p < 0.05, **p < 0.01, and ***p < 0.001 by two-sided unpaired t-test. Source data are provided as a Source Data file.