Figure 5.
SARS-CoV-2 VOCs exhibit broader organ tropism and replication capacity in WT mice
WT mice were infected i.n. with 104 pfu of the indicated SARS-CoV-2 variants on 0 days p.i.
(A) Body weight was monitored daily and is shown relative to 0 days p.i. Red dashed line indicates initial body weight (100%). Mean values of hACE2 Tg mice infected with the respective VOCs, as shown in Figure 1A, are indicated by transparent bars.
(B) AUC of the body weight, calculated for 0–5 days p.i., as shown in Figure S8A. Lung (C–E), trachea (F–H), and brain (I–K) were harvested 3 (n = 3) and 5 (Gamma) or 6 (EU-1, Alpha, Beta) (n = 4) days p.i. and analyzed for viral load by qPCR for SARS-CoV-2 N1 gene (C, F, and I), viral gene expression by qPCR for SARS-CoV-2 S gene sgmRNA (D, G, and J), and infectious viral titer by plaque assay on Vero E6 cells (E, H, and K). Shown are mean values ± SDs. Each black dot represents an individual animal. Mean values of hACE2 Tg mice infected with the respective VOCs, as shown in Figures 1C, 2A–2F, S2A, S2H, and S2N, are indicated by colored round symbols. Dashed red line indicates DL, which is 12,042 genome copies/mL for the N1 qPCR and 0 plaques/mL for the plaque assay. S gene sgmRNA is presented as 2−ΔΔCT, with 100 representing mock; down error bars are omitted in case of negative values, due to the logarithmic scale. p values were calculated performing a Kruskal-Wallis test with a Dunn’s multiple comparison test (∗p ≤ 0.05). Analysis of additional organs is shown in Figure S8. Mutations in the different SARS-CoV-2 variants that may account for the observed differences are summarized in Table S1.