Figure 1. Host Transcriptional Signatures of SARS-CoV-2 Infection as Compared to Other Respiratory Viruses.

A. Hierarchical clustering of 120 genes comprising the union of the top 50 DE genes by significance in each of the pairwise comparisons between patients with COVID-19 (SARS-CoV-2), other viral ARIs and non-viral ARIs. Group labels and viral load of SARS-CoV-2 are shown in the annotation bars. rpM, reads-per-million. B. Normalized enrichment scores of selected REACTOME pathways that achieved statistical significance (Benjamini-Hochberg adjusted p-value < 0.05) in at least one of the gene set enrichment analyses, using either DE genes between SARS-CoV-2 and non-viral ARIs or between other viruses and non-viral ARIs. If a pathway could not be tested in one of the comparisons since it had less than 10 members in the input gene set, the enrichment score was set to 0. C. in silico estimation of cell type fractions in the bulk RNA-seq using lung single cell signatures. Black lines denote the median. The y-axis in each panel was trimmed at the maximum value among the three patient groups of 1.5*IQR above the third quartile. All pairwise comparisons were performed with a two-sided Mann-Whitney-Wilcoxon test followed by Bonferroni’s correction. D. Scatter plots of normalized gene counts (log₂ scale) as a function of SARS-CoV-2 viral load, log₁₀(rpM). Robust regression was performed on SARS-CoV-2 positive patients with log₁₀(rpM) > 0 to highlight the relationship to viral load. Shown are inflammasome-related genes selected from among the genes most depressed in expression in SARS-CoV-2 compared to other viral ARIs. Statistical results for each gene refer to (from top to bottom): the regression analysis, the DE analysis between SARS-CoV-2 and non-viral ARIs, and the DE analysis between SARS-CoV-2 and other viral ARIs.