The pancreas is a target of SARS-CoV-2, according to a new study published in Nature Metabolism. The authors found that SARS-CoV-2 replicates within the islets of Langerhans and that, following infection, there are reduced numbers of insulin-secretory granules in β-cells. Importantly, the authors also show that SARS-CoV-2 infection leads to impaired glucose-stimulated insulin secretion.
In a previous study in which the authors characterized SARS-CoV-2 infection and tropism in gastrointestinal tissue, they also found that two cellular factors that are targeted by SARS-CoV-2 (ACE2 and TMPRSS2) are expressed in pancreatic tissue. Reports that identified metabolic disorders and new-onset diabetes mellitus in patients with COVID-19 spurred the authors to look into the susceptibility of islets of Langerhans to SARS-CoV-2 infection.
The authors worked with islets of Langerhans isolated from uninfected patients and exposed the islets to SARS-CoV-2. The team also applied immunohistochemistry to check for receptor expression in healthy human pancreatic tissue and for the presence of SARS-CoV-2 proteins in pancreata of four patients who had died as a result of COVID-19.
“When we checked for presence of SARS-CoV-2 in pancreatic tissues, it was astonishing that we detected infected pancreata in the biopsy samples of all four patients who died with COVID-19,” adds Kleger. “What was most striking is that in our experiments, as well as in infected tissue of patients, the infected cells within the islets of Langerhans appeared insulin negative but stained positive for endocrine markers.” The authors’ data suggest that β-cells might lose their identity and thus their function upon infection.
the islets of Langerhans appeared insulin negative but stained positive for endocrine markers
The authors now want to identify at what stage of the disease infections of the pancreas occur, whether this is a transient effect or whether patients who have had COVID-19 have pancreatic infection-induced consequences such as diabetes mellitus.
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Müller, J. A. et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat. Metab. https://doi.org/10.1038/s42255-021-00347-1 (2021)
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Morris, A. Effects of pancreatic SARS-CoV-2 infection identified. Nat Rev Endocrinol 17, 192 (2021). https://doi.org/10.1038/s41574-021-00481-6
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DOI: https://doi.org/10.1038/s41574-021-00481-6
