Extended Data Fig. 5: Anti-IFNAR2 and Remdesivir combined therapy reverses fibrotic transcriptional signature and prevents the transition to fibrosis seen in the infected mice (matched to figure 1).
From: Inflammasome activation in infected macrophages drives COVID-19 pathology
a. Relative expression of IFNG in treated or untreated MISTRG6-hACE2 mice infected with SARS-CoV-2 mice at 14 d.p.i. or 28 d.p.i. Uninfected baseline expression values are presented as reference. Normalized to HPRT1. Uninfected n = 7; CTRL infected: 14 d.p.i. n = 7, 28 d.p.i. n=: 6; Dex 14 d.p.i. = 3, 28 d.p.i. = 5; anti-IFNAR2+ Remdesivir 14 d.p.i. n = 4, 28 d.p.i. n = 6 biologically independent mice examined over at least 2 independent experiments. Unpaired, two-tailed t-test. b. Heatmap of AT2 cell self-renewal and AT1 differentiation and pre-alveolar type 1 transitional cell state (PATS) associated genes at in uninfected or infected (14 d.p.i.) lungs in response to therapeutics. AT2 cell self-renewal and AT1 differentiation gene signature was inhibited while PATS gene signature was enriched in autopsy lungs of patients with severe COVID-197. Top differentially expressed genes in epithelial cluster 7 of autopsy lungs7 were used in the analysis. Duplicates were analysed for each condition. Normalized counts of duplicates visualized as min-max transformed values, calculated by subtracting row mean and diving by SD for each gene. Rows (genes) clustered by hierarchical clustering (one-minus Pearson). c. Representative images of trichrome staining and box and whisker plot (min to max, with all datapoints) of the trichrome scoring of MISTRG6-hACE2 mice treated with a combined therapy of Remdesivir and anti-IFNAR2 or not (CTRL infected). The whiskers go down to the smallest value (minimum) and up to the largest value (maximum). The box extends from the 25th to 75th percentiles. The median is shown as a line in the center of the box. N = 4 biologically independent mice examined over 2 independent experiments. Unpaired, two-tailed t-test.
