Research output: Contribution to journal › Article › peer-review
Viral infiltration of pancreatic islets in patients with COVID-19. / Steenblock, Charlotte; Richter, Stefanie; Berger, Ilona; Barovic, Marko; Schmid, Janine; Schubert, Undine; Jarzebska, Natalia; von Mässenhausen, Anne; Linkermann, Andreas; Schürmann, Annette; Pablik, Jessica; Dienemann, Thomas; Evert, Katja; Rodionov, Roman N.; Semenova, Natalia Y.; Zinserling, Vsevolod A.; Gainetdinov, Raul R.; Baretton, Gustavo; Lindemann, Dirk; Solimena, Michele; Ludwig, Barbara; Bornstein, Stefan R.
In: Nature Communications, Vol. 12, No. 1, 3534, 10.06.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Viral infiltration of pancreatic islets in patients with COVID-19
AU - Steenblock, Charlotte
AU - Richter, Stefanie
AU - Berger, Ilona
AU - Barovic, Marko
AU - Schmid, Janine
AU - Schubert, Undine
AU - Jarzebska, Natalia
AU - von Mässenhausen, Anne
AU - Linkermann, Andreas
AU - Schürmann, Annette
AU - Pablik, Jessica
AU - Dienemann, Thomas
AU - Evert, Katja
AU - Rodionov, Roman N.
AU - Semenova, Natalia Y.
AU - Zinserling, Vsevolod A.
AU - Gainetdinov, Raul R.
AU - Baretton, Gustavo
AU - Lindemann, Dirk
AU - Solimena, Michele
AU - Ludwig, Barbara
AU - Bornstein, Stefan R.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/6/10
Y1 - 2021/6/10
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Angiotensin-Converting Enzyme 2/metabolism
KW - Autopsy
KW - COVID-19/pathology
KW - Diabetes Complications/pathology
KW - Diabetes Mellitus/pathology
KW - Dipeptidyl Peptidase 4/metabolism
KW - Female
KW - HMGN Proteins/metabolism
KW - Humans
KW - Insulin-Secreting Cells/metabolism
KW - Male
KW - Middle Aged
KW - Neuropilin-1/metabolism
KW - Organ Specificity/physiology
KW - Receptors, Coronavirus/metabolism
KW - SARS-CoV-2/isolation & purification
KW - Serine Endopeptidases/metabolism
KW - SYSTEM
KW - TMPRSS2
KW - DOWNSTREAM
KW - NECROPTOSIS
KW - MLKL
KW - ACE2
KW - EXPRESSION
KW - ENTRY FACTORS
UR - http://www.scopus.com/inward/record.url?scp=85107527595&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/76ed6caa-9f04-3f2a-8488-913038be060e/
U2 - 10.1038/s41467-021-23886-3
DO - 10.1038/s41467-021-23886-3
M3 - Article
C2 - 34112801
AN - SCOPUS:85107527595
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3534
ER -
ID: 87888221