GLP-1 Drugs Show Promise Against Long COVID-Related Lung Scarring

GLP-1 agonists have become widely used to treat type 2 diabetes and support weight loss, with growing evidence suggesting they may offer additional health benefits. Now, findings from mouse studies published in the Journal of Virology suggest the drugs could also benefit people with type 2 diabetes who develop pulmonary fibrosis months or years after contracting SARS-CoV-2, the virus that causes COVID-19.

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People with diabetes have way more severe infections and infection-related severe disease after COVID-19 than other people.

Runhong Zhou, PhD, Study Leader and Virologist, University of Hong Kong

Zhou investigates how viruses and the immune system interact. According to previous studies, patients with diabetes are four times more likely than people with no diabetes to experience severe Long COVID symptoms, but the exact mecahanisms remain unknown, he added.

He further added, “We wanted to know why these people have long-term symptoms.”

The primary cause of pulmonary fibrosis, a lung disease marked by extensive scarring, is immune cells known as macrophages. It is one of the most severe manifesatations of Long COVID, a term used to describe a variety of long-term health issues that may continue following a COVID-19 infection. In addition to causing severe coughing and other symptoms, the thickened lung tissue prevents oxygen from diffusing into the bloodstream.

Since the start of the SARS outbreak in China in November 2002, Chen has been researching animal immune responses and the immunopathogenesis of coronaviruses.

To further understand how type 2 diabetes contributes to pulmonary symptoms in Long COVID, Zhou and his colleagues analyzed blood samples collected from people with and without diabetes at three different time periods following admission to a hospital for treatment.

The researchers discovered varying amounts of monocytes, which are white blood cells that can mature into macrophages, at the third time point, months following hospitalization. The researchers discovered varying amounts of monocytes, which are white blood cells that can mature into macrophages, at the third time point, months following hospitalization. Additionally, they found elevated activity in monocyte-related genetic pathways associated with the development of fibrosis in individuals with diabetes.

The connections between diabetes, SARS-CoV-2 infection, and the development of pulmonary fibrosis were then investigated further using experiments in mice. For instance, those investigations revealed that several fibrosis-related genes, which normally produce the fibrous proteins the body requires, were excessively active in the mice, just as they had been in infected individuals. Finding a means to intervene with those pathways was the next stage, according to Zhou.

We wanted to figure out what kind of treatment may prevent this in the mouse.

Runhong Zhou, PhD, Study Leader and Virologist, University of Hong Kong

The GLP-1 receptor is extensively expressed in lung cells, he said, and throughout the study, he noticed previous laboratory experiments revealing that GLP-1 agonists had an anti-inflammatory impact on pneumonia-related fibrosis. However, he had not seen it tested in animal models following a severe COVID-19 infection.

They discovered that treating mice with GLP-1 agonists restored fibrosis-related genes, thereby “reprogramming” the macrophages that produced scar tissue accumulation. Treated mice had less pulmonary fibrosis than those not treated with GLP-1 agonists, indicating that the treatment may minimize the likelihood of fibrous buildup.

Zhou warned that the latest findings were preliminary. They demonstrated proof of concept and only used a limited number of mice, but the results gave him hope that the treatment is worth investigating.

Though the global emergency caused by COVID-19 has subsided, many people continue to face long-term health issues.

Long COVID is a continuous issue, and especially a lot of elderly people are still suffering from this.

Zhiwei Chen, PhD, Virologist, University of Hong Kong

Chen stated that his group has produced a series of antibody drugs that show potential against the condition.

He concluded, “So, to find a solution to help these patients is an important issue.”