a) Heatmap of 161 differentially expressed genes at day 0 (FDR < 0.01, |log(fold change)| >1) in at least one of 11 cell types. CD4+ T cells (T4), CD8+ T cells (T8), natural killer cells (NK), B cells (B), plasmablasts (PB), classical monocytes (cM), non-classical monocytes (ncM), and conventional dendritic cells (cDC) are shown. Each row represents a gene and each column is the average expression of the genes in a particular sample across all cells of a specific type. Samples are grouped by both cases control status and C19+ severity. Expression levels are row standardized. Genes are grouped by cluster with the enriched clusters annotated. b) Matrix plot of type I and type II-specific ISGs defined using an orthogonal scRNA-seq data set (left plot) and in the COMET cohort separated by case control status and disease severity (right). c) Type I and type II-specific ISG scores (y-axis) at day 0 across 4 myeloid cell types, and pseudobulk of all other cell types, separated by case control status and disease severity. Boxplots show median, 25th and 75th percentile. Cell types comprising the pseudobulk are in supplementary materials. d) Type I-specific ISG score (y-axis) over the course of disease for healthy controls, C19− and C19+ cases in classical monocytes. C19+ cases are separated by severity and the presence of anti-IFN-α2 antibodies. *** p < 0.001, ** p < 0.01, * p < 0.05, ns = not significant.