The Role of Neuropeptide Galanin, Insulin Resistance, and Inflammation in Long COVID’s Chronic Fatigue Syndrome
Nikhil Prasad Fact checked by:Thailand Medical News Team Mar 09, 2025 14 hours, 3 minutes ago
Medical News: Unraveling the Complexities of Long COVID and Chronic Fatigue Syndrome
Researchers worldwide have been investigating the lingering effects of COVID-19, particularly Long COVID, a condition characterized by persistent symptoms such as fatigue, depression, and cognitive impairment. A recent study by scientists from the University of Kufa, University of Al-Ameed, and Al-Muthanna University in Iraq, in collaboration with institutions from China, Thailand, Bulgaria, and Korea, sheds light on how neuropeptide galanin, insulin resistance, and inflammation contribute to chronic fatigue syndrome (CFS) in Long COVID patients.
The Role of Neuropeptide Galanin, Insulin Resistance, and Inflammation in Long COVID’s Chronic Fatigue Syndrome
A Groundbreaking Study on Long COVID and Neuropsychiatric Symptoms
Long COVID patients frequently report a range of neuropsychiatric symptoms, including anxiety, depression, and profound fatigue. These symptoms, collectively termed the physio-affective phenome, are believed to arise due to immune-inflammatory pathways and metabolic disturbances. This
Medical News report delves into the latest research, which identifies specific biomarkers linked to these symptoms.
The study examined 90 individuals - 60 Long COVID patients and 30 controls - three to six months post-infection. Researchers measured multiple biomarkers, including C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1), insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), S100B, and neuron-specific enolase (NSE).
Key Findings: The Biochemical Links to Chronic Fatigue and Mood Disorders
1. Higher Levels of Inflammation in Long COVID Patients
Patients with Long COVID exhibited significantly higher levels of CRP, PGE2, and PAI1, confirming an ongoing inflammatory response. PGE2, a molecule that modulates immune function, was markedly increased, potentially impairing the body’s antiviral response and increasing susceptibility to persistent infections. Elevated CRP levels were directly correlated with fatigue and mood disturbances.
2. Neuropeptide Galanin and its Receptor Play a Central Role
The study revealed that galanin and GALR1 levels were significantly elevated in Long COVID patients. Galanin is known for its regulatory role in the central nervous system, affecting mood, pain perception, and immune function. This increase in galanin signaling was associated with higher anxiety, depression, and fatigue scores, indicating its possible role in the persistence of neuropsychiatric symptoms.
3. Metabolic Dysfunction and Insulin Resistance
Insulin resistance was found to be another critical factor contributing to Long COVID symptoms. The HOMA2-IR index, which measures insulin resistance, was significantly higher in Long COVID patients compared to controls. Elevated insulin levels were linked to increased levels of neur
oinflammatory markers such as S100B and NSE, which are associated with neurodegeneration and cognitive decline.
The Connection Between Acute COVID Severity and Long-Term Symptoms
One of the most striking findings was the correlation between peak body temperature (PBT) and oxygen saturation (SpO2) levels during the acute phase of infection and the severity of Long COVID symptoms. Patients who experienced more severe inflammation during their initial infection had higher GAL-GALR1 signaling, insulin resistance, and inflammatory biomarker levels months later.
A composite PBT/SpO2 index was developed to predict the likelihood of developing Long COVID symptoms. The inclusion of this index improved the predictive accuracy of CFS and mood disorders from 33.6%-42.0% to 55.3%-67.1%.
Potential Therapeutic Implications
Given these findings, targeting immune-inflammatory pathways, insulin resistance, and neuropeptide signaling may offer new treatment strategies for Long COVID. Potential therapeutic approaches include:
-Anti-inflammatory agents (such as PGE2 inhibitors and CRP-targeting drugs)
-Metformin or other insulin-sensitizing drugs to counteract insulin resistance
-Galanin receptor modulators to regulate neuroinflammation and mood disorders
Conclusion
This study provides compelling evidence that chronic fatigue syndrome in Long COVID is driven by a complex interplay of inflammation, metabolic dysfunction, and neuropeptide signaling. The findings underscore the need for targeted treatments that address both immune and metabolic dysregulation in Long COVID patients. Future research should explore long-term treatment strategies and the potential role of antiviral therapies in mitigating persistent symptoms.
The study findings were published in the peer-reviewed journal: PLOS ONE.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0316373
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