Young hamsters and aged hamsters were infected with SARS-CoV-2. Lungs were collected at 3 dpi, 7 dpi and 22 dpi (n = 3–6). Left and middle: quantification of viral RdRp and E protein transcript levels using RT–PCR assays. The data are expressed as ΔCt and genome copy per microgram of RNA. Right: number of infectious virus particles per lung (50% tissue culture infectious dose, TCID50). b, Immunohistochemistry analysis of spike. Scale bars, 20 μm. c, Leftl: immunofluorescence staining for DAPI (blue) and viral nucleoprotein (red) is shown. Scale bars, 25 μm. Right: the intensity of nucleoprotein signals was normalized by DAPI count. The histograms indicate the fold change relative to average intensity in young animals (n = 6). d, Gene expression was quantified by RT–PCR (fold change relative to average gene expression in young animals) (n = 3–6). e, Expression of AC2 and β-tubulin in young and aged whole lung homogenates as assessed by western blotting. Right: the relative protein levels normalized to β-tubulin are shown (n = 6–8). f, Body weight loss curves (four aged hamsters and six young hamsters). g, Histopathological examination of lung sections (H&E staining). The mean sum of the subscores is shown (n = 3–6). h, Representative photomicrographs at 7 dpi. Arrowhead: inflammatory cell infiltrate; star: alveolar wall rupture; sun: type II pneumocyte hyperplasia; thunderbolt: necrosis. Scale bars, 50 μm. i, Numbers of inflammatory foci per lung section (n = 6). j, Percentage of Sirius Red labeling (n = 5–10). a–i, One of two representative experiments is shown. j, A pool of two independent experiments is depicted. For all graphs, errors indicate mean ± s.d. Significant differences were determined using the two-tailed Mann–Whitney U-test (a,c,d,e,g,i) and the one-way ANOVA Kruskal–Wallis test (non-parametric), followed by Dunn’s post test (j). Significance of body weight regain (area under the curve) in infected young hamsters was calculated using the Wilcoxon matched-pairs signed-rank test (f). *P < 0.05, **P < 0.01, ***P < 0.001.
Source data