On Sept. 13, 2024, researchers from Weill Cornell Medicine have used a cutting-edge model system to uncover the mechanism by which SARS-CoV-2, the virus that causes COVID-19, induces new cases of diabetes, and worsens complications in people who already have it. The research team found that viral exposure activates immune cells that in turn destroy beta (β) cells, the pancreatic cells that produce insulin. The study results were published in Cell Stem Cell.

From the early days of the COVID-19 pandemic, doctors caring for sick patients observed that the virus affected a number of organ systems, including not only the lungs, but also the heart, liver, colon and pancreas. For the current work, the researchers started with samples of pancreatic tissue from autopsies of people who had died of COVID-19. They observed that the pancreatic islets, the parts of the pancreas that generate the insulin to regulate blood sugar, were damaged.

They then used an analysis technique called GeoMx to study the samples in more detail. This revealed the presence of immune cells called proinflammatory macrophages in the tissues. The job of these macrophages is to kill off pathogens, but they sometimes cause collateral damage to healthy tissues.

To learn more about this activity, the team used a model system developed in the Chen Lab that had never been used before; pancreatic islet organoids (mini organs) that included both a vascular system and immune cells. “If we want to use organoids to study how a disease progresses, it’s important to be able to include components of the immune system in these models,” said Dr. Chen. In this case, after infecting the organoids with SARS-CoV-2, they found the macrophages appeared to be killing off the β cells through a type of cell death called pyroptosis.

The team also used the organoids to study how the pancreas responds to infection with another infectious virus — coxsackievirus B4, which has been implicated in the onset of type 1 diabetes. They found a similar macrophage response. “Moving forward, this organoid system is going to be useful for looking at other viruses as well,” Dr. Schwartz said.

Further research on the signaling molecules that activate the macrophages also suggested potential interventions for protecting β cells from damage in patients with severe infections. Although it is too early to begin testing any treatments, this is something that may be possible in the future. This work could also help shed light on the underlying causes of long COVID, a condition that is believed to affect more than 15 million people in the United States.

The research reported in this story was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.