A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we found ACE2 expression in endothelial cells to be extremely low or absent in vivo and not upregulated by exposure to inflammatory agents in vitro. Also, the endothelial chromatin landscape at the ACE2 locus showed presence of repressive and absence of activation marks, suggesting that the gene is inactive in endothelial cells. Finally, we failed to achieve infection and replication of SARS-CoV-2 in cultured human endothelial cells, which were permissive to productive infection by coronavirus 229E that uses CD13 as the receptor. Our data suggest that SARS-Cov-2 is unlikely to infect endothelial cells directly; these findings are consistent with a scenario where endothelial injury is indirectly caused by the infection of neighbouring epithelial cells and/or due to systemic effects mediated by immune cells, platelets, complement activation, and/or proinflammatory cytokines.

中文翻译：

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在人内皮细胞中缺乏ACE2表达和SARS-CoV-2复制感染的证据

严重的COVID-19的显着特征是多器官的大血管和小血管中的血栓形成。这导致了这样一个假设，即SARS-CoV-2病毒会直接感染并损害血管内皮。然而，尚未令人信服地证明了ACE2（SARS-CoV-2的细胞受体）的内皮表达。审视人类大量和单细胞转录组学数据，我们发现内皮细胞在体内的ACE2表达极低或不存在，并且在体外暴露于炎症剂后不会上调。另外，ACE2基因座处的内皮染色质景观显示存在抑制性和激活标记，这表明该基因在内皮细胞中无活性。最后，我们未能在培养的人内皮细胞中实现SARS-CoV-2的感染和复制，它们允许使用CD13作为受体的冠状病毒229E进行生产性感染。我们的数据表明，SARS-Cov-2不太可能直接感染内皮细胞。这些发现与内皮损伤是由邻近上皮细胞的感染和/或由于免疫细胞，血小板，补体激活和/或促炎性细胞因子介导的全身性作用间接引起的情况一致。