Researchers Uncover How Myostatin and Irisin May Drive Persistent Exhaustion in COVID-19 Survivors
Nikhil Prasad Fact checked by:Thailand Medical News Team May 22, 2025 6 hours, 2 minutes ago
Medical News: Fatigue is one of the most persistent and debilitating symptoms experienced by people recovering from COVID-19, and a new Brazilian study is shedding light on why it lingers long after the virus has left the body. Scientists have discovered that this post-COVID fatigue, often called long COVID, may be tied to harmful changes in certain muscle-regulating proteins—myostatin and irisin—that disrupt the body’s energy metabolism.
Researchers Uncover How Myostatin and Irisin May Drive Persistent Exhaustion in COVID-19 Survivors
The groundbreaking research was conducted by experts from several institutions, including the Thoracic Disease Institute and the Carlos Chagas Filho Institute of Biophysics at the Federal University of Rio de Janeiro, the Biomedical Institute at Fluminense Federal University in Niterói, and the Department of Medicine at the State University of Ponta Grossa. This
Medical News report dives into the findings and what they mean for long COVID patients worldwide.
One in Three COVID-19 Survivors Still Fatigued Months Later
The study evaluated 88 patients who had been hospitalized for COVID-19 and followed up with them at least four months after their discharge. Out of these, 34 percent reported new or worsening fatigue—despite showing no significant differences in lung function, heart function, or diaphragm condition compared to those without fatigue.
Interestingly, ICU admission during their initial illness stood out as the only independent risk factor for developing long-term fatigue. Those who had been in the ICU were more than twice as likely to experience persistent exhaustion. This suggests that the physical toll of critical illness, rather than the virus alone, may be a key driver of lingering symptoms.
No Lung or Heart Abnormalities Detected
Contrary to what one might expect, extensive testing revealed no clear damage to lung function or heart performance in patients suffering from post-COVID fatigue. Lung ultrasounds and diaphragm function tests also showed no substantial differences between fatigued and non-fatigued individuals. This indicates that fatigue is not necessarily tied to damage in major organs traditionally associated with energy production and breathing.
The Real Culprits Myostatin and Irisin
The most striking discovery was that patients with fatigue had significantly elevated blood levels of two biomarkers—myostatin and irisin. Both are proteins produced in muscles and fat tissue and are involved in regulating energy balance and muscle growth.
Myostatin is a known inhibitor of muscle development. High levels of this protein have previously been linked to muscle wasting and weakness in critically ill patients. Its presence in higher concentrations among fatigued COVID survivors suggests their muscles may not be regenerating or functioning properly, even months after recovery.
Irisin, on the other hand, i
s typically associated with energy regulation and has anti-inflammatory properties. It is released during exercise and has protective effects on muscles and metabolism. However, the study found that sustained high levels of irisin might reflect a dysfunctional attempt by the body to counteract muscle damage. Instead of helping, its overproduction may signal chronic muscle stress or metabolic imbalance.
Reduced Quality of Life Across the Board
Patients reporting fatigue also showed significantly lower scores on the SF-36 health survey—a widely used tool for assessing quality of life. Key areas affected included vitality, general health, social functioning, mental health, and emotional well-being. This paints a bleak picture of the long-term consequences of COVID-19 for many patients, with fatigue deeply affecting both physical and psychological aspects of daily life.
Even two years after infection, many continued to report these symptoms, underscoring the chronic nature of post-COVID fatigue. Surprisingly, neither age, gender, vaccination status, nor the variant they were infected with (Delta, Omicron, or original strain) had a significant influence on who developed fatigue.
Muscle Dysfunction as a Hidden Epidemic
The researchers argue that the persistence of fatigue is likely due to long-term disruptions in muscle metabolism rather than damage to the lungs or heart. This hypothesis could transform how doctors understand and treat long COVID. Rather than focusing solely on respiratory recovery, physicians may need to shift attention to muscle rehabilitation and metabolic therapy.
Elevated myostatin and irisin could serve as vital biomarkers to identify patients at risk and monitor their recovery. Furthermore, these findings open the door to potential treatments. For example, drugs that block myostatin could help restore muscle function, while structured exercise programs might help balance irisin levels and improve energy metabolism.
Conclusion
The findings from this comprehensive Brazilian study present a new and compelling explanation for why some COVID-19 survivors continue to experience overwhelming fatigue long after their infection. Rather than being caused by lung or heart damage, the root of the problem appears to lie in the body’s muscles—specifically in how they respond to severe illness and stress. Elevated levels of myostatin and irisin are now identified as key contributors to post-COVID fatigue, especially among those who were admitted to the ICU. This research highlights the importance of monitoring muscle health and developing targeted therapies that focus on restoring muscle function and energy balance in long COVID patients. As the pandemic’s long shadow continues to affect millions globally, understanding the biology behind fatigue is essential to guiding both recovery and public health responses.
The study findings were published in the peer reviewed journal: Frontiers in Medicine
https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1547886/full
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