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. New-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients, however, the underlying mechanisms are not fully understood. Here, the authors show that SARS-CoV-2 is detectable in both endocrine and exocrine cells of the pancreata of patients with COVID-19.
【저자키워드】 viral infection, diabetes, 【초록키워드】 SARS-CoV-2, immunohistochemistry, ACE2, severe COVID-19, Infection, diabetes, Autopsy, DPP4, RNA, Immune cell infiltration, electron microscopy, Viral, Microscopy, virus entry, Factors, Complication, NRP1, vasculature, receptor, immunofluorescence, TMPRSS, hyperglycemia, disease, expression, patients, mechanism, COVID-19 patients, infiltration, Endocrine, COVID-19 patient, Metabolic diseases, dysregulation, pseudoviruses, islet cells, metabolic, tissue, increased risk, comprehensive analysis, SARS-CoV-2 pseudoviruses, necroptotic cell death, pancreatic beta-cells, SARS-CoV-2 viral infection, Cell, SARS-CoV-2 viral, performed, examined, detectable, facilitate, contribute, absence, expressed, diabete, islet cell, pancreatic, pancreatic beta-cell, patients with COVID-19, 【제목키워드】 Viral, infiltration, pancreatic islet, patients with COVID-19,