Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets.
Moufida Ben NasrFrancesca D'AddioLaura MontefuscoVera UsuelliCristian LoretelliAntonio RossiIda PastoreAhmed AbdelsalamAnna MaestroniMarco Dell'AcquaElio IppolitoEmma AssiAndy Joe SeelamRoberta Maria FiorinaEnrica ChebatPaola MorpurgoMaria Elena LunatiAndrea Mario BollaReza AbdiJoseph V BonventreStefano RusconiAgostino RivaDomenico CorradiPierachille SantusPamela ClarkManuela NebuloniGabriella BaldiGiovanna FinziFranco FolliGian Vincenzo ZuccottiMassimo GalliKevan C HeroldPaolo FiorinaPublished in: Diabetes (2022)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- endothelial cells
- end stage renal disease
- cell death
- induced pluripotent stem cells
- chronic kidney disease
- ejection fraction
- type diabetes
- single cell
- rheumatoid arthritis
- oxidative stress
- skeletal muscle
- bone marrow
- risk assessment
- cell free
- prognostic factors
- insulin resistance
- deep learning
- electronic health record
- big data
- sensitive detection
- artificial intelligence
- neoadjuvant chemotherapy
- adipose tissue
- machine learning
- signaling pathway
- living cells
- weight loss
- single molecule
- circulating tumor cells
- mass spectrometry