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ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas

Irina Kusmartseva, Wenting Wu, Farooq Syed, Verena Van Der Heide, Marda Jorgensen, Paul Joseph, Xiaohan Tang, Eduardo Candelario-Jalil, Changjun Yang, Harry Nick, Jack L. Harbert, Amanda Posgai, Richard Lloyd, Sirlene Cechin, Alberto Pugliese, Martha Campbell-Thompson, Richard S. Vander Heide, Carmella Evans-Molina, Dirk Homann, View ORCID ProfileMark A. Atkinson
doi: https://doi.org/10.1101/2020.08.31.270736
Irina Kusmartseva
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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Wenting Wu
2Indiana University School of Medicine, Center for Diabetes and Metabolic Diseases,, Indianapolis, Indiana, 46202, USA
3Indiana University School of Medicine, Herman B. Wells Center for Pediatric Research, Indianapolis, Indiana, 46202, USA
4Department of Medical and Molecular Genetics, Indianapolis, Indiana, 46202, USA
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Farooq Syed
2Indiana University School of Medicine, Center for Diabetes and Metabolic Diseases,, Indianapolis, Indiana, 46202, USA
3Indiana University School of Medicine, Herman B. Wells Center for Pediatric Research, Indianapolis, Indiana, 46202, USA
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Verena Van Der Heide
5Department of Medicine, Mt. Sinai School of Medicine, New York, New York, USA
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Marda Jorgensen
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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Paul Joseph
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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Xiaohan Tang
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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Eduardo Candelario-Jalil
6Department of Neuroscience, College of Medicine, Gainesville, Florida 32610, USA
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Changjun Yang
6Department of Neuroscience, College of Medicine, Gainesville, Florida 32610, USA
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Harry Nick
6Department of Neuroscience, College of Medicine, Gainesville, Florida 32610, USA
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Jack L. Harbert
7Department of Pathology, Louisiana State University, New Orleans, Louisiana, USA
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Amanda Posgai
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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Richard Lloyd
8Department of Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
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Sirlene Cechin
9Deparment of Medicine, College of Medicine, Diabetes Research Institute, University of Miami, Miami, Florida, USA
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Alberto Pugliese
9Deparment of Medicine, College of Medicine, Diabetes Research Institute, University of Miami, Miami, Florida, USA
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Martha Campbell-Thompson
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
10Department of Biomedical Engineering, University of Florida, College of Engineering, Gainesville, Florida 32610, USA
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Richard S. Vander Heide
7Department of Pathology, Louisiana State University, New Orleans, Louisiana, USA
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Carmella Evans-Molina
2Indiana University School of Medicine, Center for Diabetes and Metabolic Diseases,, Indianapolis, Indiana, 46202, USA
3Indiana University School of Medicine, Herman B. Wells Center for Pediatric Research, Indianapolis, Indiana, 46202, USA
11Roudebush VA Medical Center, Indianapolis, Indiana, 46202, USA
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Dirk Homann
5Department of Medicine, Mt. Sinai School of Medicine, New York, New York, USA
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Mark A. Atkinson
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
12Department of Pediatrics, University of Florida Diabetes Institute, College of Medicine, Gainesville, Florida 32610, USA
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  • ORCID record for Mark A. Atkinson
  • For correspondence: atkinson@ufl.edu
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SUMMARY

Diabetes is associated with increased mortality from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq pancreas datasets and performed fluorescence in situ hybridization, Western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas
Irina Kusmartseva, Wenting Wu, Farooq Syed, Verena Van Der Heide, Marda Jorgensen, Paul Joseph, Xiaohan Tang, Eduardo Candelario-Jalil, Changjun Yang, Harry Nick, Jack L. Harbert, Amanda Posgai, Richard Lloyd, Sirlene Cechin, Alberto Pugliese, Martha Campbell-Thompson, Richard S. Vander Heide, Carmella Evans-Molina, Dirk Homann, Mark A. Atkinson
bioRxiv 2020.08.31.270736; doi: https://doi.org/10.1101/2020.08.31.270736
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ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas
Irina Kusmartseva, Wenting Wu, Farooq Syed, Verena Van Der Heide, Marda Jorgensen, Paul Joseph, Xiaohan Tang, Eduardo Candelario-Jalil, Changjun Yang, Harry Nick, Jack L. Harbert, Amanda Posgai, Richard Lloyd, Sirlene Cechin, Alberto Pugliese, Martha Campbell-Thompson, Richard S. Vander Heide, Carmella Evans-Molina, Dirk Homann, Mark A. Atkinson
bioRxiv 2020.08.31.270736; doi: https://doi.org/10.1101/2020.08.31.270736

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