Molecular consequences of SARS-CoV-2 liver tropism

Extrapulmonary manifestations of COVID-19 have gained attention, not only due to their links to clinical outcomes, but also due to their potential long-term sequelae. Recent evidence has shown multi-organ tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including heart, kidney and liver. Previous studies have shown that close to 20% of hospitalized patients with COVID-19 develop liver injury, showing an association to disease severity. Here, we characterized SARS-CoV-2 liver tropism in autopsy samples, based on the expression of cell-entry facilitators in parenchymal cells, clinical polymerase chain reaction (PCR) positivity, subgenomic SARS-CoV-2 identification using RNA sequencing, and viral RNA detection by in situ hybridization. Next, we unraveled the transcriptomic  landscape of SARS-CoV-2 liver tropism, revealing significant increases in interferon alpha and gamma signaling and compensatory liver-specific metabolic regulation. While these results reflect changes in tissues from patients with severe SARS-CoV-2 infection, the profound molecular alterations raise questions about the potential long-term consequences of COVID-19 infection.

COVID-19的肺外表现已受到广泛关注，不仅因其与临床结局相关，还因其潜在的长期后遗症。近期证据表明，严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）具有多器官嗜性，包括心脏、肾脏和肝脏。既往研究显示，近20%的COVID-19住院患者会发生肝损伤，且这与疾病严重程度相关。本研究基于实质细胞中细胞进入辅助因子的表达、临床聚合酶链式反应（PCR）阳性结果、通过RNA测序鉴定亚基因组SARS-CoV-2以及通过原位杂交检测病毒RNA，对尸检样本中的SARS-CoV-2肝脏嗜性进行了表征。随后，我们解析了SARS-CoV-2肝脏嗜性的转录组图谱，发现α和γ干扰素信号通路显著增强，且存在代偿性肝脏特异性代谢调控。尽管这些结果反映了重症SARS-CoV-2感染患者组织中的变化，但这些深刻的分子改变也引发了关于COVID-19感染潜在长期后果的疑问。