SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (Bulk RNA-Seq)

Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-a, INF-? and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages. Overall design: Human liver organoids were differentiated from human pluripotent stem cells (hPSCs) and infected with live SARS-CoV-2 virus. Some of the samples were exposed to macrophages and treated with tocilizumab. The transcriptional changes observed were compared with hPSC derived liver organoids infected with either heat-inactivated SARS-CoV-2 virus or mock infected, either exposed or not exposed to macrophages.