Abstract 12007: RNA Sequencing Analysis Reveals A Novel Pathway Associated With The Exacerbation Of Covid-19

Abstract

Introduction: The severity of Coronavirus disease 2019 (COVID-19) depends on the host immune cell response and dysregulation. Most COVID-19 patients had mild disease, however, 15-30 % of patients developed severe disease which could result in severe acute respiratory failure and death. Risk factors associated with severe disease such as age, smoking and comorbidities are well known, while molecular signatures to predict the disease progression are still emerging. Hypothesis: Severe COVID-19 have a unique gene expression profile in peripheral blood mononuclear cells (PBMCs) at early stage of disease compared to mild disease. Methods: We used RNA sequencing analysis and pathway analysis in PBMCs collected from COVID-19 patients at a median 4 days after the onset. Subsequent clinical course was evaluated by WHO definition (meet any of oxygen saturation < 90 %, respiratory rate > 30 breaths / min and signs of severe respiratory distress or not), and based on the severity, PBMCs obtained from mild (n=6) and severe (n=6) groups were analyzed. Results: At the sample collection, there was no significant difference in clinical characteristics between groups, but laboratory tests exhibited higher C-reactive protein and lactate dehydrogenase levels in severe group compared to mild group (Table). We identified 148 differentially expressed genes (DEGs, FDR < 0.05) that are enriched for a pathway, HDACs deacetylate histone, as the top pathway using Metascape. This includes 15 genes in HIST1 cluster that has not only antimicrobial but also cytotoxic and blood coagulation effect once the proteins are released into circulation, which could result in acute lung injury. Conclusions: Our results suggest that the upregulation of HIST1 cluster genes expression in PBMCs at early stage of COVID-19 could predict the subsequent disease exacerbation. These findings may also link to the pathophysiology of COVID-19 in the context of histone protein mediated lung injury and respiratory failure.