Fig. 4: Transcriptional response to SARS-CoV-2 infection is strong in myeloid and moderate in epithelial cells.

a, b Dotplot of differentially expressed genes in lungs (a) and blood (b). Shown are genes that are in at least one cell type among the top four most changing genes as ranked by adjusted p-value. Example: top 4 most changing genes in alveolar macrophages are Ybx3, Rps15, Rps10, and Uba52. Coloration and point size indicate log2-transformed fold changes (FC) and p-values, respectively, of genes at 2 days post infection (dpi) relative to control groups (naive). Adjusted (adj.) p-values were calculated by DEseq2 using Benjamini–Hochberg corrections of two-sided Wald test p-values. Cell types and genes are ordered by unsupervised clustering. c Top, fraction of monocytic macrophages expressing Cxcl10 in blood and lungs from naive animals and 2 dpi. Bottom, boxplots of Cxcl10 gene expression values of cells positive for Cxcl10 expression. Significance levels were calculated using two-sided generalized linear mixed-effects models for bar plots and a two-sided Wilcoxon rank-sum test on all cells (i.e., not only the ones expressing the gene) for boxplots. ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.0001. See “Methods” for details. d As in (c), but only in lungs, all time points and both alveolar epithelial cells type 2 (AT2) and monocytic macrophages. Displayed are values for Isg15 (left) and Cxcl10 (right). For all bar plots, data display means ± SD, n = 3 per time point. For all boxplots, cell gene expression data derived from n = 3 animals per time point. The middle line in the boxplot displays the median, the box indicates the first and third quartile, whiskers the 1.5 interquartile range (IQR). Outliers beyond are marked by single dots. AT1 and AT2: alveolar epithelial cell type 1 and 2, DC: dendritic cells, NK, natural killer cells; d0: day 0 = naive, d14: 14 dpi. Exact p-values in (c): upper panel: ^∗∗p = 0.0022; ^∗∗∗p < 0.0001; lower panel: ^∗∗p = 0.0015; ^∗∗∗p < 0.0001.