Fig. 1: A Viral Pandemic (ViP) signature that is induced in COVID-1918, is induced also in epidemic outbreaks of KD.

a Schematic displays the computational approach (BECC) and rigor (diversity and number of datasets) used to identify the 166-gene ViP and a subset of 20-gene severe (s)ViP signatures, and the subsequent experimentally validated inferences and impact of the same in a recent study18. The numbers in gray circles denote the total number of datasets analyzed in each category. b Schematic displays the various pathogenic triggers that induce ViP signatures (many of which are triggers also for KD) and the prominent induction of IL15/IL15RA as an invariant nature of the cytokine storm. c Bubble plots of ROC-AUC values (radii of circles are based on the ROC-AUC) demonstrating the strength of classification and the direction of gene regulation (Up, red; Down, blue) for the classification based on the 20-gene severe ViP signature (top) and 166-gene ViP signature (bottom) in numerous publicly available historic datasets. ViP signatures classified KD vs. healthy children (left), acute vs. convalescent KD (middle) and treatment response in the setting of combination therapy with IV steroids (MP methylprednisone) and IV IgG alone (IVIG), but not IVIG alone. Numbers on top of bubble plots indicate number of subjects in each comparison group. d, e Bar (top) and violin (bottom) plots display the classification of blood samples that were collected during acute (AV), sub-acute (SA; ~10–14 days post-discharge) and convalescent (CV; 1 year post-onset) visits from two independent KD cohorts (d; Historic Cohort 1; e; Prospective Cohort 2) using ViP (left) or sViP (right) signatures. f Bar (top) and violin (bottom) plots display the sub-classification of blood samples in Cohort 1 based on coronary artery aneurysm (CAA) status using ViP (left) or sViP (right) signatures. Welch’s two sample unpaired two-sided t-test is performed on the composite gene signature score to compute the p values. In multi-group setting each group is compared to the first control group and only significant p values are displayed on the right. Additional pvalues are displayed on the left.