Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Institute of Virology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Nat Commun. 2021 Jun 10;12(1):3534. doi: 10.1038/s41467-021-23886-3.
Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.
代谢疾病与 COVID-19 重症风险增加相关，相反，COVID-19 患者中也观察到新发高血糖和原有糖尿病并发症。在这里，我们使用免疫荧光、免疫组织化学、RNA 原位杂交和电子显微镜对 COVID-19 患者的胰腺尸检组织进行了全面分析，在所有患者中均检测到 SARS-CoV-2 病毒对β细胞的浸润。使用 SARS-CoV-2 假病毒，我们证实分离的人胰岛细胞允许感染。在 11 名 COVID-19 患者中，我们检测了 ACE2、TMPRSS 及其他可能促进病毒进入的受体和因子，如 DPP4、HMBG1 和 NRP1 的表达。尽管 70%的 COVID-19 患者血管中表达 ACE2，但只有 30%的患者β细胞中表达 ACE2。即使没有明显的新发糖尿病，细胞坏死性死亡、免疫细胞浸润和 SARS-CoV-2 病毒对胰腺β细胞的感染，也可能导致 COVID-19 患者出现不同程度的代谢失调。
