New insights into links between SARS-CoV-2 infection and diabetes

Transmission electron microscopy image showing SARS-CoV-2, the virus that causes COVID-19.
Image credit: National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratories, NIHResearch has revealed that the virus causing COVID-19 can infect pancreatic β (beta) cells, changing their function—a critical discovery toward understanding a devastating relationship between COVID-19 and chronic disease. Despite SARS-CoV-2 being primarily a respiratory virus, it affects multiple organs and systems during acute illness and sets the stage for long-term symptoms in a significant proportion of those infected. Thus, understanding the mechanisms underlying COVID-19’s many complications and comorbidities is important to reducing the tremendous burden this disease is already imposing on people and health care systems around the world. For example, people with diabetes are at higher risk for grave outcomes from COVID-19. Moreover, researchers are trying to figure out whether SARS-CoV-2 infection may also trigger new onset of diabetes, as there is increasing evidence with the number of new cases appearing after infection. One unanswered question is whether SARS-CoV-2 exerts such effects through direct infection of susceptible cells and tissues.

In an initial study, researchers demonstrated in laboratory models how SARS-CoV-2 infects certain human cells and tissues—including pancreatic β cells and liver cells. They also found that donated human pancreatic islets were susceptible to SARS-CoV-2 infection. The team then collaborated with additional researchers to investigate whether or not β-cell infection also occurred in people infected with SARS-CoV-2, and, if so, what effects this had on the cells. Comparisons of islets from deceased human donors showed molecular signatures of SARS-CoV-2 in the β cells of those who had died from COVID-19. Closer examination of islets infected with SARS-CoV-2 in the laboratory revealed that infected β cells produced less insulin and produced proteins normally made by other pancreatic cells— suggesting that infection was causing them to change their function, or "transdifferentiate." A similar pattern of changes was also seen in islets from deceased donors with COVID-19, confirming that SARS-CoV-2 infection can alter β-cell activity in people.

Further analysis suggested that an intracellular pathway activated in response to viral infection and other stressors was governing the observed β-cell changes. Using artificially transdifferentiated human cells, the scientists identified a chemical that in subsequent experiments blocked the β-cell transdifferentiation process upon SARS-CoV-2 infection, most likely through inhibition of virus-induced changes to the identified stress-activated pathway. These results not only suggest that SARS-CoV-2 infection directly induces changes in β cells that could affect the course or onset of diabetes, but also provide hope that this process may be preventable.