1. Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets.
- Author
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Ben Nasr, Moufida, D'Addio, Francesca, Montefusco, Laura, Usuelli, Vera, Loretelli, Cristian, Rossi, Antonio, Pastore, Ida, Abdelsalam, Ahmed, Maestroni, Anna, Dell'Acqua, Marco, Ippolito, Elio, Assi, Emma, Seelam, Andy Joe, Fiorina, Roberta Maria, Chebat, Enrica, Morpurgo, Paola, Lunati, Maria Elena, Bolla, Andrea Mario, Abdi, Reza, and Bonventre, Joseph V.
- Abstract
Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (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. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1β (IL-1β), anti-IL-6, and anti-tumor necrosis factor 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, was detected in postmortem 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 islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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