Chronic fatigue syndrome (CFS) is a complex and long-term illness characterized by extreme fatigue that doesn’t improve with rest, and can worsen with physical activity. The exhaustion is severe enough to limit a person’s ability to carry out daily activities like cooking, showering, or even getting dressed. Additional symptoms can include muscle pain, joint pain, memory issues, headaches, sleep problems, and sensitivity to light or sound.
There is no known cause or cure for CFS, which affects an estimated 3.3 million people in the United States, according to the Centers for Disease Control and Prevention.
There’s also no specific diagnostic test.
“It’s a mysterious disease,” says Lehigh University researcher Xuanhong Cheng, a professor of bioengineering and materials science and engineering in the P.C. Rossin College of Engineering and Applied Science. “There are no single biological indicators that can be used to diagnose chronic fatigue syndrome, and so doctors are forced to diagnose individuals by ruling out other symptoms and conditions.”
Cheng is part of an international team of researchers who recently received funding from the National Institutes of Health to explore molecular- and cellular-level changes in muscle tissue that could potentially lead to better diagnostic tools and therapeutic options for both CFS and related conditions, such as long COVID.
“The symptoms of CFS are very similar to that of long COVID,” says Cheng. “But one of the most consistent symptoms across both diseases is muscle pain. Our collaborator [Tiziana Pietrangelo of Università degli Studi "G. d'Annunzio" Chieti – Pescara, in Italy] has studied CFS for more than a decade, and she’s found that people with the disease also have elevated oxidative stress in their muscle tissue, which contributes to why the muscle is so easily overworked.”
The team is taking a multidisciplinary approach to determine if there are biological indicators within the muscle that could potentially be used to diagnose—and potentially treat—individuals with these conditions.
Pietrangelo will explore the physiology of the skeletal muscle tissue and muscle stem cells, and the role oxidative stress may play in their functions. Stefano Cagnin, a professor from University of Padova in Italy, will study gene expression in muscle fiber and muscle stem cells, comparing the results of healthy populations with those of people who have CFS, to uncover molecular changes linked to the disease.
Cheng will examine the electrical signature of skeletal muscle stem cells. Using a technology she co-developed called broadband electrical sensing, she will examine characteristics at the cellular level that could reveal if a cell is healthy or diseased.
“We’ll try to see whether those signatures are specific enough for us to diagnose the disease,” she says.
Electrical measurements could become a valuable diagnostic tool because they are easier and less expensive than molecular analysis. However, the researchers must first establish how these electrical changes correlate with underlying molecular abnormalities, which will be revealed through the work of the other team members.
It’s a novel approach in several respects.
“When it comes to CFS, researchers have focused on a range of different tissues, organs, and mechanisms, but we’re one of the first teams to look specifically at changes in skeletal muscle stem cells,” says Cheng. “And we’re using a multidisciplinary approach so we can look at those changes from the molecular level, the subcellular organelle level, and the cellular level.”
By integrating their data, the team hopes to develop a more comprehensive understanding of how CFS affects muscles and determine whether such changes could be used as diagnostic markers or therapeutic targets.
The long-term goal, says Cheng, is to create noninvasive diagnostic tools.
“For example, using an electrode at a certain frequency could allow you to see some kind of abnormal output indicating pathology in their muscle,” she says. “This could be used as an indicator for diagnosing CFS.”
Additionally, by pinpointing the molecular changes that contribute to the disease, the team hopes to eventually explore therapeutic strategies, which could, for instance, alleviate oxidative stress and improve patients’ symptoms.
While such advances are a long way off, any progress will be welcome news to the millions who suffer from a disease that has long been misunderstood—and often maligned.
“Because CFS has been so poorly understood, the people who have it were sometimes called lazy, or told their symptoms were all in their head,” says Cheng. “I think long COVID has, unfortunately, made people more aware that these symptoms are actually very real, and they can arise after a viral infection. We’re happy to see that change in thinking, and we’re looking forward to helping these people restore their health.”
About Xuanhong Cheng
Xuanhong Cheng is a professor of bioengineering and materials science and engineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science. Her research focuses on developing innovative micro- and nanoscale technologies for disease diagnosis and treatment, particularly in point-of-care diagnostics and biosensing. Cheng’s interdisciplinary work, leading the Lab of Micro- and Nanotechnology for Diagnostics and Biology, bridges engineering and biology, aiming to create tools that improve healthcare delivery in resource-limited settings. She has published extensively in leading scientific journals and collaborates with researchers across various fields to advance biomedical research.
Cheng earned her PhD in bioengineering from the University of Washington, where she specialized in biomaterials and nanotechnology. Her work encompasses areas such as the development of biosensors for pathogen detection, lab-on-a-chip systems, and microfluidic devices for rapid diagnostics. She is committed to translating cutting-edge technologies into real-world applications and has been recognized for her contributions to both the engineering and biomedical fields.
