Figure 3.
Brain pathology in transgenic mice infected with SARS-CoV-2. Mice were infected with 2.5 × 104 pfu NG-SARS-CoV-2 via IN. (A) IVM images (original magnification ×20) of the brains of hACE2 AC70 and hACE2 K18 mice uninfected and infected with NG-SARS-CoV-2 showing infected neurons (green) (day 5 after infection). Scale bars, 12 μm (left and middle), 20 μm (right). (B) IVM images (original magnification ×20) of the brains of hACE2 AC70 mice uninfected and infected with NG-SARS-CoV-2. Anti-Ly6G (AL488) was injected IV during the acquisition of the image to make sure the neutrophils were not infected. Scale bars, 12 μm. (C) IVM image (original magnification ×20) of the brain of hACE2 AC70 mice infected with NG-SARS-CoV-2. Anti-Ly6G (AL488) was injected IV during the acquisition of the image showing neutrophils (green) (day 5 after infection). The arrow indicates a neutrophil entering the brain parenchyma. Scale bar, 12 μm. (D) IVM images (original magnification ×20) of the brains of hACE2 AC70 mice uninfected and infected with NG-SARS-CoV-2 after the administration of 70 000 MW dextran-rhodamine. Scale bars, 23 μm (left) and 12 μm (right). The graph represents the percentage of permeability of the blood vessels in the brain. (E) IVM images (original magnification ×20) of the brains of hACE2 AC70 mice uninfected and infected with NG-SARS-CoV-2 showing platelets (anti-CD49b, blue) (day 5 after infection). Scale bars, 12 μm (left) and 25 μm (right). The graph represents the quantification of the % of the blood vessel lumen covered by platelets. (F) IVM images (original magnification ×20) of the brains of hACE2 AC70 mice infected with NG-SARS-CoV-2 showing platelets (anti-CD49b, blue) and neutrophils (anti-Ly6G, green) in the vasculature (day 5 after infection). Anti-Ly6G (AL488) was injected IV during the acquisition of the image to make sure the neutrophils were not infected. Scale bar, 12 μm. Data (as applicable) are represented as mean ± SD. Unpaired Student t test was performed for statistical analysis. ∗P < .05; ∗∗∗∗P < .001.