SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
The study titled “SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment” explores the relationship between COVID-19 and diabetes, focusing on the infection of pancreatic β cells by SARS-CoV-2 and its consequences.
Here’s a detailed summary:
Background: The study investigates whether SARS-CoV-2, the virus causing COVID-19, can infect insulin-producing pancreatic β cells, potentially leading to diabetes. This is based on clinical observations of increased diabetes symptoms in COVID-19 patients.
SARS-CoV-2 Entry Factors in β Cells: The study found that β cells in the pancreas express the SARS-CoV-2 receptors ACE2 and TMPRSS2, although at low levels. However, the expressions of neuropilin 1 (NRP1) and transferrin receptor (TFRC), also implicated in SARS-CoV-2 entry, were notably higher in β cells compared to other pancreatic cell types. This finding suggests a possible mechanism for the virus’s targeted infection of β cells.
Infection of β Cells in Laboratory Settings: The study demonstrated that SARS-CoV-2 preferentially infects β cells in isolated human pancreatic islets. This was evidenced by the presence of the virus in β cells but not in other types of pancreatic cells, such as α and δ cells, or endothelial cells.
Infection in COVID-19 Patients: Autopsy samples from COVID-19 patients revealed SARS-CoV-2 infection in the pancreatic β cells. Out of nine patients studied, seven showed viral positivity in their pancreas, with the virus detected specifically in the β cells of four patients.
Impact on β Cell Function: The infection led to a significant reduction in insulin content and glucose-stimulated insulin secretion (GSIS) in the infected islets. This suggests that SARS-CoV-2 infection can impair pancreatic function, potentially leading to diabetes-like symptoms. Moreover, the study found that β cells undergo apoptosis (cell death) following infection, further contributing to the dysfunction.
Discussion: The study underscores the importance of understanding how SARS-CoV-2 affects pancreatic function, given the observed increase in diabetes symptoms among COVID-19 patients. The selective expression of SARS-CoV-2 entry factors like NRP1 and TFRC in β cells appears to facilitate the virus’s infection of these cells, leading to pancreatic dysfunction and potential diabetes onset. However, the study notes that the virus’s effects on β cells are not necessarily the sole cause of diabetes in COVID-19 patients, as autoimmune responses could also play a role.
Limitations: The study acknowledges limitations such as the reliance on protein expression analyses in pancreatic tissue sections, which only provide approximate predictions for susceptibility to SARS-CoV-2 infection. The study’s findings from isolated human islets could not be directly translated to the clinical samples due to the lack of corresponding patient data on insulin and blood glucose levels. Additionally, the phosphoproteomics analysis covered all islet cell types, not just β cells, limiting the ability to pinpoint cell-specific signaling pathways affected by the virus.
Overall, this study provides critical insights into the potential direct impact of SARS-CoV-2 on pancreatic β cells, offering a mechanistic link between COVID-19 and the development of diabetes symptoms.