Research May Improve Treatment of Fatigue Associated with Long COVID-19


Study shows that the nervous system of individuals experiencing post-COVID-19 fatigue is underactive in 3 key areas.

A research breakthrough by investigators from Newcastle University may improve the treatment of fatigue among individuals with long COVID-19, according to a study published in Brain Communications.

Credit: fizkes -

Credit: fizkes -

“Much of our current research and understanding on the acute and chronic impacts of SARS-CoV-2 is centered on the inflammatory and immunological effects following an infection, which in turn can affect many other systems in the body,” the study authors wrote.1 “Indeed, there is mounting evidence that inflammatory markers remain elevated several months after an infection for patients with the longer term sequelae, but the relationship between inflammation and [post-COVID fatigue (pCF)] remains unclear.”

The study found that the nervous system of individuals experiencing post-COVID-19 fatigue was underactive in 3 key areas, which may lead to improved treatments and tests to identify the condition. The 3 areas identified were a slower reaction in specific areas of the brain because of underactivity in certain cortical circuits; an imbalance in the autonomic nervous system, which can have a significant effect on several different body processes; and muscle abnormalities that cause fibers to become more easily fatigued following exercise compared with people without post-COVID fatigue.

“These abnormalities in the results on objective tests show that fatigue in long COVID is a measurable disease and these tests may, in time, help us understand how changes in the nervous system contribute to fatigue,” said lead researcher Dr Demetris Soteropoulos, senior lecturer in Motor Systems Neuroscience at Newcastle University, in a press release.2

The investigators have begun recruiting patients to evaluate the efficacy of a TENS machine, which is typically used for pain relief associated with childbirth, to mitigate fatigue experienced by patients with long-COVID. The investigators estimated that 1.9 million people are currently experiencing long-COVID-19 and approximately half those individuals identified fatigue as their main symptom.

Although most patients with COVID-19 don't experience severe illness and recover quickly, some individuals develop long-term problems post-infection regardless of the severity of their initial illness.

“Fatigue appears to be a multisystem pathology associated with immunological, metabolic and hormonal anomalies,” the authors wrote in the study.1 “There are strong links between the immune and nervous systems with multiple pathways for possible interactions.”

The study authors evaluated a group of 37 individuals with post-COVID-19 fatigue. Participants were administered several well-established non-invasive behavioral and neurophysiological tests, the results of which were compared to 52 age- and sex-matched control. The tests produced 33 sets of data, including a startle reaction time test, electrocardiogram, and transcranial magnetic stimulation.

“Fatigue could arise from a reduced ability of the neuromuscular apparatus to generate force; a given movement would then require stronger voluntary drive and perceived effort would rise,” the study authors wrote.1 “Changes could arise in the muscles themselves, due to a weakened connection from motoneurons to muscle fibres, or because motoneurons are less excitable. We found that maximal grip strength (Grip) was not significantly reduced in pCF, suggesting no deficit in force production for brief contractions.”

The study authors concluded that the results show evidence of dysregulation in all 3 main divisions of the nervous system, provided via tests that may be easily incorporated into future trials to assess and treat pCF. They added that it is yet to be determined whether the results are applicable to other post-viral fatigue syndromes and chronic fatigue.

“We know that many people have faced criticism or even disbelief when they report long Covid, so by being able to provide an independent measure, we can help medical teams provide continued support,” said study co-author Dr Anne Baker, in a press release.2


1. Neural Dysregulation in Post-COVID Fatigue. Anne M.E. Baker, Natalie J. Maffitt, Alessandro Del Vecchio, Katherine M. McKeating, Mark R. Baker, Stuart N. Baker and Demetris S. Soteropoulos. Brain Communications

2. New research sheds light on the causes of fatigue after COVID 19. News release. Newcastle University. May 11, 2023.

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