Viral infiltration of pancreatic islets in patients with COVID-19.
Adult
Aged
Angiotensin-Converting Enzyme 2
/ metabolism
Autopsy
COVID-19
/ pathology
Diabetes Complications
/ pathology
Diabetes Mellitus
/ pathology
Dipeptidyl Peptidase 4
/ metabolism
Female
HMGN Proteins
/ metabolism
Humans
Insulin-Secreting Cells
/ metabolism
Male
Middle Aged
Neuropilin-1
/ metabolism
Organ Specificity
/ physiology
Receptors, Coronavirus
/ metabolism
SARS-CoV-2
/ isolation & purification
Serine Endopeptidases
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 06 2021
10 06 2021
Historique:
received:
13
01
2021
accepted:
06
05
2021
entrez:
11
6
2021
pubmed:
12
6
2021
medline:
23
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34112801
doi: 10.1038/s41467-021-23886-3
pii: 10.1038/s41467-021-23886-3
pmc: PMC8192507
doi:
Substances chimiques
HMGN Proteins
0
NRP1 protein, human
0
Receptors, Coronavirus
0
Neuropilin-1
144713-63-3
DPP4 protein, human
EC 3.4.14.5
Dipeptidyl Peptidase 4
EC 3.4.14.5
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
HPN protein, human
EC 3.4.21.106
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3534Références
J Pediatr Endocrinol Metab. 2020 Nov 12;34(1):147-150
pubmed: 33180050
Clin Gastroenterol Hepatol. 2020 Aug;18(9):2128-2130.e2
pubmed: 32334082
Expert Opin Drug Saf. 2016;15(4):457-65
pubmed: 26789102
Cell. 2021 Jan 7;184(1):76-91.e13
pubmed: 33147444
Am J Emerg Med. 2020 Nov;38(11):2491.e3-2491.e4
pubmed: 32536476
Cell. 2012 Jan 20;148(1-2):213-27
pubmed: 22265413
J Endocrinol Invest. 2020 Jul;43(7):1027-1031
pubmed: 32361826
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Endocr Rev. 2014 Dec;35(6):992-1019
pubmed: 25216328
Nat Metab. 2021 Feb;3(2):149-165
pubmed: 33536639
Nat Metab. 2020 Oct;2(10):1021-1024
pubmed: 32879473
Diabetologia. 2020 Oct;63(10):2102-2111
pubmed: 32647915
Acta Diabetol. 2010 Sep;47(3):193-9
pubmed: 19333547
Science. 2020 Nov 13;370(6518):856-860
pubmed: 33082293
Cell Metab. 2020 Dec 1;32(6):1041-1051.e6
pubmed: 33207244
JCI Insight. 2018 Feb 8;3(3):
pubmed: 29415896
Front Endocrinol (Lausanne). 2020 Nov 13;11:596898
pubmed: 33281748
Life Sci. 2006 Apr 4;78(19):2166-71
pubmed: 16303146
Cell Metab. 2020 Dec 1;32(6):1028-1040.e4
pubmed: 33207245
Mol Ther. 2014 Aug;22(8):1460-1471
pubmed: 24814152
Immunity. 2013 Sep 19;39(3):443-53
pubmed: 24012422
Cell Metab. 2020 Jun 2;31(6):1068-1077.e3
pubmed: 32369736
Cell. 2017 Apr 6;169(2):286-300.e16
pubmed: 28388412
Nature. 2015 Jan 15;517(7534):311-20
pubmed: 25592536
Mol Psychiatry. 2020 Aug;25(8):1611-1617
pubmed: 32382135
Curr Ther Res Clin Exp. 2020;93:100609
pubmed: 33132404
J Virol. 2016 Dec 16;91(1):
pubmed: 27795420
Diabetes Res Clin Pract. 2020 Jun;164:108166
pubmed: 32339533
Nat Metab. 2021 Feb;3(2):123-125
pubmed: 33432203
Diabetes Obes Metab. 2020 Oct;22(10):1935-1941
pubmed: 32314455
Int J Environ Res Public Health. 2020 Aug 17;17(16):
pubmed: 32824596
Horm Metab Res. 2015 Jan;47(1):4-8
pubmed: 25083718
Cells. 2020 Nov 13;9(11):
pubmed: 33202960
N Engl J Med. 2020 Aug 20;383(8):789-790
pubmed: 32530585
Gastroenterology. 2014 Apr;146(4):1097-107
pubmed: 24361123
Diabetes. 1988 Apr;37(4):413-20
pubmed: 3288530
Cell Mol Life Sci. 2017 Jan;74(1):173-181
pubmed: 27535660
Microorganisms. 2020 Jul 27;8(8):
pubmed: 32727064
Mol Ther. 2012 Jun;20(6):1167-76
pubmed: 22472951
N Engl J Med. 2014 Jan 30;370(5):455-65
pubmed: 24476434
Oncoimmunology. 2020 Oct 27;9(1):1838812
pubmed: 33178497
J Endocr Soc. 2020 Jul 02;4(8):bvaa082
pubmed: 32728654
J Diabetes Complications. 2020 Sep;34(9):107637
pubmed: 32456846
Biol Sex Differ. 2017 Feb 3;8:5
pubmed: 28174624
Cell Stem Cell. 2020 Jul 2;27(1):125-136.e7
pubmed: 32579880
BMJ Case Rep. 2020 Sep 7;13(9):
pubmed: 32900752
iScience. 2020 Jun 26;23(6):101160
pubmed: 32405622
Endocr Rev. 2020 Jun 1;41(3):
pubmed: 32294179
Nat Rev Endocrinol. 2020 Jun;16(6):297-298
pubmed: 32242089
Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94
pubmed: 12892317