Fig. 5: Alveolar differentiation intermediate (ADI) cells in SARS-CoV-2-infected hamsters.

a Quantification of cytokeratin 8 (CK8)⁺ alveolar differentiation intermediate (ADI) cells within the whole alveolar space and within alveolar epithelial proliferation (ep. prol.) foci. On the right, representative pictures of immunolabeling (brown signal) in the alveoli of SARS-CoV-2- and mock-infected hamsters at 6 days post infection (dpi). b Representative image of triple immunofluorescence in an alveolar proliferation focus at 6 (left panel) and 28 (right panel) dpi. Cells are labeled with CK8 (green), pro-Surfactant protein C (proSP-C, light blue), and Podoplanin (Pdpn, red). In the left picture at 6 dpi there are either round proSP-C⁺CK8⁻PDPN⁻ or proSP-C⁺CK8⁺PDPN⁻ cells (arrows and inlet) in the alveolar proliferation focus. In the right picture at 28 dpi there are moderate numbers of elongated proSP-C⁻CK8⁺PDPN⁺ (arrow and inlet) in the alveolar proliferation focus. Scattered proSP-C⁻CK8⁺PDPN⁻ and numerous proSP-C⁻CK8⁻PDPN⁺ cells are seen at both time points. The staining was performed in four animals/time points with the same results. c Heatmap of normalized expression values for genes associated with ADI cells (Supplementary Table 1) at each dpi in mock- and SARS-CoV-2-infected hamsters. Expression values are scaled by row. Red indicates higher and blue lower relative expression levels. a Data are shown as box and whisker plots. The bounds of the box plot indicate the 25th and 75th percentiles, the bar indicates medians, and the whiskers indicate minima and maxima. Dots indicate individual values. Statistical analysis was performed by a two-tailed Mann–Whitney U test. For multiple comparisons between time points (quantification within alveolar proliferation foci), a Benjamini–Hochberg correction was applied. P- and q values ≤ 0.05 were considered significant. N = 8 animals/group (a) or 4 animals/group (c). Source data is provided as a Source Data file.