COVID‐19 and non‐alcoholic fatty liver disease: Biological insights from multi‐omics data

Abstract

AbstractWe explored the shared pathophysiological mechanisms between COVID‐19 and non‐alcoholic fatty liver disease (NAFLD) by integrating multi‐omics data. We studied common genetic risk factors and underlying biological processes using functional enrichment analysis. To understand the sex‐specific pathways involved in the clinical course of SARS‐CoV‐2 infection, we processed sex‐stratified data from COVID‐19 genome‐wide association datasets. We further explored the transcriptional signature of the liver cells in healthy and COVID‐19 tissue specimens. We also integrated genetic and metabolomic information. We found that COVID‐19 and NAFLD share biological disease mechanisms, including pathways that regulate the inflammatory and lipopolysaccharide response. Single‐cell transcriptomics revealed enrichment of complement‐related pathways in Kupffer cells, syndecan‐mediated signalling in plasma cells, and epithelial‐to‐mesenchymal transition in hepatic stellate cells. The strategy of pathway‐level analysis of genomic and metabolomic data uncovered l‐lactic acid, Krebs cycle intermediate compounds, arachidonic acid and cortisol among the most prominent shared metabolites.