Systematic temporal analysis of peripheral blood transcriptomes usingTrendCatcheridentifies early and persistent neutrophil activation as a hallmark of severe COVID-19

Abstract

A recent analysis of endothelial cell (EC) gene expression suggests that ECs of distinct organs vary in their gene expression profiles and respond distinctly to the systemic inflammatory stimulus of endotoxemia (Jambusaria et al., 2020). There is a need to systematically define tissue-specific gene expression dynamics in response to inflammation but such an analysis is in part limited by the availability of appropriate algorithms to analyze differential expression across a time course. Here, we present TrendCatcher (https://jaleesr.github.io/TrendCatcher_1.0.0/), an R package designed for time course RNA-seq data analysis which identifies distinct dynamic transcriptional programs. When applied to ECs, we observed that approximately 85-95% of EC genes in all three organs followed a biphasic response following endotoxemia. The rapid upregulation of innate immune response and bacterial response genes occurred within 6 hours in all three vascular beds but the subsequent upregulation of reparative EC mitosis and cell cycle genes occurred most rapidly in lung ECs (24-48h) and was most delayed in cardiac ECs (72h-168h). The distinct kinetics of EC inflammatory injury and regeneration identify vascular-bed specific temporal windows for targeted therapeutics.