FIG 5.

Comparative temporal analysis of SARS-CoV-2 MA10 and USA-WA1/2020 replication and pathological alterations in the brain (cerebral cortex) of K18-hACE2 mice. Infectious viral particles (A) and viral RNA (B) were quantified in the brain of infected mice at 2, 4, and 6 dpi. Histological scores (C) and percentage of SARS-CoV-2 immunoreactivity (D) in the brain of K18-hACE2 mice is shown. Bars represent the mean ± standard deviation. Dotted line represents the limit of detection. Temporal histologic lesions (E to L) and viral antigen abundance and distribution (M to T) in the brain of K18-hACE2 mice. Histologic changes are noted as early as 4 dpi and are more pronounced on the MA10-infected group (G) with delicate perivascular lymphocytic cuffs (G, inset a), sporadic pyknotic nuclei, and increased microglial cells and scattered neutrophils within the neuroparenchyma (G, inset b). At this time point, viral antigen is significantly more abundant in the MA10-infected group compared to that of the group infected with the parental USA-WA1/2020 strain. As previously reported, neuronal vacuolation/necrosis are prominent at 6 dpi (H and L) with diffuse and abundant expression of viral antigen within neuronal bodies and processes (P and T) with cerebellar sparing as previously reported. H&E (E to H) and Fast Red (viral antigen) (I to L); ×200 total magnification. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.