In the spring of 2020, doctors in New York, the U.S. epicenter of the pandemic at the time, noticed a significant number of people hospitalized with COVID-19 with too much blood sugar, a condition called hyperglycemia, which is a hallmark of diabetes.
“[My colleagues and I] found it very challenging to control blood glucose levels in some patients with COVID-19, even those without a history of diabetes, ”said stem cell biologist Shuibing Chen of Weill Cornell Medicine. More surprisingly, Chen says, some patients who did not have diabetes before the infection developed new diabetes after recovering from COVID-19.
The COVID-19 virus, SARS-CoV-2, is best known for causing chaos in the lungs and causing acute respiratory distress. But how and why a patient with COVID-1
A 2020 global analysis conducted by population health researcher Thirunavukkarasu Sathish of McMaster University in Canada found that nearly 15% of severe patients with COVID-19 also developed diabetes. But, he admits, “this figure is likely to be higher among high-risk individuals, such as prediabetes.” Studies conducted by endocrinologist Paolo Fiorina of Harvard Medical School and published in 2021 report that of the 551 patients hospitalized for COVID-19 in Italy, almost half become hyperglycemic.
Peter Jackson, a biochemist at Stanford University School of Medicine, estimates that “up to 30 percent of patients with severe COVID-19 can develop diabetes.”
Intrigued by the startling link between COVID-19 and diabetes, Chen and Jackson launched independent investigations to find out how SARS-CoV-2 can cause hyperglycemia. Both groups published their results in the May issue of Cellular metabolism.
“The findings give them a critical picture of the main mechanisms by which COVID-19 can lead to the development of new-onset diabetes in infected patients,” said Rita Callani, an associate professor of medicine in the Hopkins Department of Endocrinology, Diabetes and Metabolism. has participated in any study.
The pancreas is another target of the COVID-19 virus
SARS-CoV-2 affects humans in many different ways. Many people experience only minor symptoms, but others develop a severe, life-threatening illness. As the pandemic unfolded, it became clear that the virus could spread beyond the lungs and damage other important organs, including the liver, heart and kidneys. It has also been shown that diabetes and obesity are common risk factors for severe COVID-19.
In an earlier study, Chen’s group grew different types of tissue in the lab and tested those that were vulnerable to the COVID-19 virus. “Surprisingly, we found that pancreatic beta cells are highly susceptible to SARS-CoV-2 infection,” says Chen. The pancreas, which is located behind the stomach, is a complex organ composed of many types of cells that help digestion. It also contains beta cells, which produce insulin, the hormone that accompanies blood sugar molecules in the body’s cells, where it is used for energy.
But the fact that the virus can infect cells grown in a laboratory dish does not mean that it attacks the body in the same way. To ensure that laboratory observations were a true reflection of what was happening to living people, Chen and Jackson’s teams took autopsy samples from patients who had succumbed to COVID-19. Both groups found SARS-CoV-2 in pancreatic beta cells from these deceased patients.
But how exactly does the respiratory virus move from the lungs to the pancreas? Once patients develop pneumonia, the lower lung infection can cause tissue damage that allows the virus to escape from the alveoli of the lungs and blood vessels, Jackson explains. “Once in circulation, the virus can enter other highly vascularized tissues such as the pancreas, brain and kidneys.” Others suggest that the virus can enter the bloodstream through leaks from the gut, which can occur in patients without healthy intestinal bacteria. (Intestinal microbes can be rookies in the fight against viruses)
How the virus stops producing insulin
Both research teams noted that beta cells infected with SARS-CoV-2 stopped producing insulin. In Jackson’s study, infected beta cells died by apoptosis, a genetically programmed sequence for automatic destruction initiated by damaged cells.
Chen’s group found that infected beta cells had undergone a process called transdifferentiation, meaning they had transformed into another type of cell; one that no longer produces insulin. It is possible that some infected beta cells undergo transdifferentiation while others self-destruct.
In both cases, the end result is the same: when the COVID-19 virus attacks pancreatic beta cells, insulin production decreases.
This can lead to type 1 diabetes, which is usually caused by genetic risk factors that stimulate an autoimmune response that attacks and destroys beta cells. Type 1 diabetes is more common in early life and requires patients to inject insulin every day because their bodies no longer produce the hormone. Type 1 diabetes also involves triggering the environment, such as an infection, to initiate an autoimmune response.
In contrast, far more common type 2 diabetes occurs when the body becomes resistant to the insulin it produces. Type 2 diabetes can be managed with changes in diet and exercise, although drugs that improve insulin sensitivity are sometimes needed. A total of 34.2 million Americans have diabetes, according to a 2020 report released by the Centers for Disease Control.
The fate of infected beta cells is important for further study, as there may be a way to prevent their destruction in patients with severe COVID-19. Chen’s team is researching a large panel of chemicals in hopes of finding one that will prevent the process of transdifferentiation.
The study identified a compound called trans-ISRIB that helps beta cells retain their identity and ability to produce insulin when infected with SARS-CoV-2. Trans-ISRIB, which means Integrated Stress Response InhiBitor, is a compound discovered in 2013 that is able to prevent the cell’s normal response to stress. Such compounds are being investigated as potential therapeutic agents for the prevention of widespread apoptosis and damage.
Chen warns, “Trans-ISRIB is not an FDA-approved drug, so it still cannot be used in patients. But our research supports the idea that a new drug could be developed to prevent COVID-19 from causing diabetes. “Jackson’s group found that a cellular protein receptor called neuropilin-1 is crucial for SARS-CoV-2 to invade beta cells; blocking this receptor prevents them from becoming infected.
There is also great interest among the wider research community in developing drugs that stop cells from being destroyed by apoptosis. Experimental compounds called caspase inhibitors, which prevent cell suicide, have been studied by others as potential therapies to improve or prevent severe COVID-19. Unfortunately, caspase inhibitors have not proven complete success in the clinic despite great promise and interest. However, “they can work for short-term exposure to limit viral damage,” Jackson said.
Chen added that SARS-CoV-2 is not the only virus that threatens the pancreas. “Coxsackievirus B, rotavirus, mumps virus and cytomegalovirus have been shown to infect and damage beta cells. Whether they are a direct cause of type 1 diabetes is controversial. “More research is needed to determine whether it is possible to neutralize the viral attacks of the pancreas, either by blocking the infection or preventing the virus from reaching the organ in the first place.
Kaliani emphasizes that these studies “further emphasize the importance of vaccination against COVID-19. People who contract COVID-19, especially those with prediabetes or other risk factors for diabetes, should inform their healthcare providers if they develop symptoms of hyperglycaemia such as frequent urination, excessive thirst, blurred vision or unexplained weight loss. “
These new findings underscore that there is much to be learned about COVID-19 and its implications. It seems clear that for some unfortunate people, defeating the virus is just the beginning. Additional complications can occur depending on which systems in the body have been damaged after a viral infection.