Nikhil Prasad Fact checked by:Thailand Medical News Team May 19, 2026 50 minutes ago
Medical News: Researchers from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health in Bethesda, Maryland, along with the NIH Clinical Center, have uncovered what may be one of the strongest biological clues yet behind Long COVID and chronic fatigue syndrome. Their new study found that patients suffering from post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) and Long COVID appear to share a serious deficiency involving norepinephrine, a critical brain chemical linked to energy, focus, alertness, and physical stamina.
Scientists discover a major norepinephrine deficiency in Long COVID and chronic fatigue syndrome patients
linked to fatigue and post-exertional crashes
The findings could help explain why so many patients experience crushing exhaustion, “brain fog,” weakness, and worsening symptoms after even minor activity.
A Brain Chemical Linked to Energy and Alertness
Norepinephrine is a neurotransmitter that helps the brain regulate attention, stress responses, physical activity, and energy production. Researchers examined spinal fluid samples from patients with Long COVID, chronic fatigue syndrome, Parkinson’s disease, and healthy volunteers to compare levels of important brain chemicals.
The study showed that both Long COVID and chronic fatigue syndrome patients had significantly lower activity in what scientists called the “Norepinephrine Pathway.” This pathway included norepinephrine and two related metabolic compounds known as DHPG and MHPG. The reduction was similar to abnormalities already seen in Parkinson’s disease patients.
Importantly, the researchers did not find the same kind of deficiency in dopamine-related pathways. This suggests that the problem is highly specific to norepinephrine rather than being part of a general brain chemical failure.
Why Patients Feel Worse After Activity
One of the most important discoveries involved post-exertional malaise, the hallmark symptom where patients become dramatically worse after physical or mental effort.
Among Long COVID patients, those suffering from post-exertional malaise had especially low norepinephrine pathway activity compared to healthy individuals. Researchers believe this may explain why many patients crash after exercise, social interaction, or even basic daily tasks.
The scientists also found that lower norepinephrine activity was closely tied to poorer grip strength, shorter endurance during handgrip testing, more severe fatigue, and worse overall health scores.
Patients with lower levels of this neurotransmitter pathway consistently reported reduced vitality, lower physical functioning, and worsening mental and emotional wellbeing.
This
Medical News report highlights that the abnormality may not just be psychological or stress-related, but instead could reflect a measurable biological dysfunction within the b
rain itself.
Possible Clues About What Causes the Problem
The researchers proposed a possible explanation involving cellular energy production.
Producing norepinephrine inside nerve cells requires energy in the form of ATP, the body’s main cellular fuel. The team speculated that Long COVID and chronic fatigue syndrome may interfere with the brain’s ability to properly generate or use ATP. If cells lack sufficient energy, they may struggle to produce and store norepinephrine correctly.
This theory could also explain other symptoms commonly reported by patients, including severe fatigue, muscle weakness, exercise intolerance, and poor recovery after activity.
Interestingly, the study found no strong relationship between norepinephrine deficiency and pain, memory problems, anxiety, or depression. Instead, the chemical abnormality appeared to be most strongly linked with physical exhaustion and overall health decline.
Study Included Multiple Patient Groups
The investigation involved 122 participants in total, including healthy volunteers, Long COVID patients, chronic fatigue syndrome patients, and Parkinson’s disease patients.
Researchers carefully collected cerebrospinal fluid through lumbar punctures and measured neurotransmitter chemicals using advanced laboratory techniques. The work was conducted under several NIH-approved clinical research protocols.
The authors included Lillian Aregawi, Brian Walitt, Patti Sullivan, Gina Norato, Rohit Ninan Benjamin, and David S. Goldstein from the National Institute of Neurological Disorders and Stroke and the NIH Clinical Center.
Findings Could Shape Future Treatments
The researchers stressed that the study does not yet prove that norepinephrine deficiency directly causes Long COVID or chronic fatigue syndrome. However, the evidence strongly suggests it plays an important role.
Future studies may investigate whether treatments that improve norepinephrine signaling or boost cellular energy production can reduce symptoms. Scientists may also begin exploring whether spinal fluid neurotransmitter testing could eventually help identify patients with these debilitating conditions.
The conclusions of the study are particularly significant because Long COVID and chronic fatigue syndrome have long lacked reliable biological markers. Many patients have struggled for years with skepticism about the legitimacy of their illness. These findings provide growing scientific evidence that measurable neurological abnormalities are present and may contribute directly to the disabling symptoms experienced by millions worldwide. The study also opens the door for more targeted therapies focused on restoring brain energy balance and neurotransmitter function rather than simply managing symptoms.
The study findings were published in the peer reviewed journal: Brain
Communications.
https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcag173/8677724
For the latest on
Long COVID, Keep on logging to Thailand
Medical News
Read Also:
https://www.thailandmedical.news/articles/long-covid
Share
Tweet
Share
