GLP-1 Agonists Show Promise in Reducing Pulmonary Fibrosis from Long COVID in Diabetic Patients, Mouse Study Finds
Key Insights
GLP-1 agonists (search) may reduce pulmonary fibrosis (search) in people with type 2 diabetes (search) suffering from Long COVID (search), according to new mouse model research published in the Journal of Virology.
People with diabetes face a risk of severe Long COVID (search) symptoms that is four times higher than those without diabetes, though the underlying mechanisms remain poorly understood.
Treated mice showed normalized fibrosis-related genes and reduced lung scarring compared to untreated mice, suggesting GLP-1 agonists (search) can "reprogram" macrophages responsible for scar tissue buildup.
GLP-1 agonists (search), widely known as treatments for weight loss and type 2 diabetes (search), may offer therapeutic benefits to an additional patient population: individuals with type 2 diabetes who develop pulmonary fibrosis (search) months or years after SARS-CoV-2 (search) infection. Findings from experiments on mice, published this week in the Journal of Virology, suggest these drugs could reduce the lung scarring that characterizes one of the most severe manifestations of Long COVID (search).
"People with diabetes have way more severe infections and infection-related severe disease after COVID-19 than other people," said virologist and study leader Runhong Zhou, Ph.D., at the University of Hong Kong, who studies interactions between viruses and the immune system. Studies have estimated that people with diabetes face a risk of severe Long COVID (search) symptoms that is four times higher than people who don't have diabetes, he said, but the mechanisms aren't well understood. "We wanted to know why these people have long-term symptoms."
The Link Between Diabetes, COVID-19, and Pulmonary Fibrosis (search)
Pulmonary fibrosis (search) is a lung disease characterized by widespread scarring, primarily caused by immune cells called macrophages. The thickened tissue inhibits the diffusion of oxygen into the bloodstream and can cause severe coughing and other symptoms. It is among the most severe symptoms of Long COVID (search), a condition describing myriad persistent health problems that can linger after COVID-19 infection.
During this study, Zhou was a researcher in the lab of virologist Zhiwei Chen, Ph.D., also at the University of Hong Kong, who has been studying immune responses and immunopathogenesis of coronaviruses in animals since the SARS outbreak in China that began in November 2002.
To better understand how type 2 diabetes (search) contributes to pulmonary symptoms in Long COVID (search), Zhou and his collaborators first compared blood samples from people with and without diabetes at three distinct time points after hospital admission for COVID-19 treatment. At the third time point, months after hospitalization, the researchers found differing levels of monocytes — white blood cells that can develop into macrophages. In people with diabetes, they also identified increased activity in genetic pathways involving monocytes that are linked to the onset of fibrosis.
Mouse Experiments Confirm the Connection
The researchers then used experiments on mice to confirm the connections among diabetes, SARS-CoV-2 (search) infection, and the onset of pulmonary fibrosis (search). Those experiments showed that numerous fibrosis-related genes — which under normal conditions are responsible for fibrous proteins the body needs — were overly active in the mice, mirroring what had been observed in infected people.
The next step was to find a way to interfere with those pathways. "We wanted to figure out what kind of treatment may prevent this in the mouse," Zhou said. The GLP-1 receptor (search) is highly expressed in lung cells, he noted, and during the study he observed other laboratory experiments reporting that GLP-1 agonists (search) showed some anti-inflammatory effect against fibrosis related to pneumonia. However, the approach had not been tested in animal models after severe COVID-19 infection.
Reprogramming Macrophages to Reduce Scarring
Treating the mice with GLP-1 agonists (search) normalized the fibrosis-related genes, effectively "reprogramming" the macrophages that caused the scar tissue buildup. Treated mice showed reduced pulmonary fibrosis (search) compared to those not treated with GLP-1 agonists, suggesting that the drug could lessen the risk of fibrous buildup.
Zhou cautioned that the new findings are preliminary. They show proof of concept and only involved a small number of mice, but the findings gave him optimism that the treatment is worth investigating.
Long COVID (search) Remains a Persistent Challenge
Though the global emergency spurred by COVID-19 has lessened, long-term health problems continue to affect many people. "Long COVID (search) is a continuous issue, and especially a lot of elderly people are still suffering from this," Chen said, noting that his lab developed a suite of antibody drugs that show promise against the condition. "So, to find a solution to help these patients is an important issue."