Recent studies have shown that SARS-CoV-2 infection may induce metabolic distress, leading to hyperglycemia in patients affected by COVID-19. We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. While there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which can be abrogated by the use of anti-IL1β, anti-IL-6 and anti-TNF-α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19, revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, were detected in post-mortem pancreatic tissues, suggestive of β-cell altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islets function and survival by creating inflammatory conditions and possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.

Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets / M.B. Nasr, F. D'Addio, L. Montefusco, V. Usuelli, C. Loretelli, A. Rossi, I. Pastore, A. Abdelsalam, A. Maestroni, M. Dell'Acqua, E. Ippolito, E. Assi, A.J. Seelam, R.M. Fiorina, E. Chebat, P. Morpurgo, M.E. Lunati, A.M. Bolla, R. Abdi, J.V. Bonventre, S. Rusconi, A. Riva, D. Corradi, P. Santus, P. Clark, M. Nebuloni, G. Baldi, G. Finzi, F. Folli, G.V. Zuccotti, M. Galli, K.C. Herold, P. Fiorina. - In: DIABETES. - ISSN 0012-1797. - 71:7(2022), pp. 1579-1590. [10.2337/db21-0926]

Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets

M.B. Nasr
Primo
;
F. D'Addio
Secondo
;
L. Montefusco;V. Usuelli;C. Loretelli;A. Rossi;I. Pastore;A. Abdelsalam;A. Maestroni;M. Dell'Acqua;E. Ippolito;E. Assi;A.J. Seelam;P. Morpurgo;M.E. Lunati;S. Rusconi;A. Riva;P. Santus;M. Nebuloni;F. Folli;G.V. Zuccotti;M. Galli;P. Fiorina
Ultimo
2022

Abstract

Recent studies have shown that SARS-CoV-2 infection may induce metabolic distress, leading to hyperglycemia in patients affected by COVID-19. We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. While there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which can be abrogated by the use of anti-IL1β, anti-IL-6 and anti-TNF-α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19, revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, were detected in post-mortem pancreatic tissues, suggestive of β-cell altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islets function and survival by creating inflammatory conditions and possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.
Settore MED/13 - Endocrinologia
Settore MED/50 - Scienze Tecniche Mediche Applicate
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/928010
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