ME/CFS & Long COVID Studies
List of Medical Research and Science Articles on Post-Acute Infection Sequelae from the 1950s to Today
I’ve put together a list of medical studies on post-infection syndromes, ME/CFS, and long COVID. I’ll keep adding new ones. Patients are often told by doctors that there’s nothing physically wrong with them because standard tests are fine. But there could be markers to look out for. The problem is, this area has been starved of research funding for decades. Hopefully, this list helps out doctors, patients, and anyone advocating for better understanding.
2025
Preprint — Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS
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Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome
DecodeME collaboration | Published — 6 Aug 2025
Research output: Working paper › Preprint
Summary:
ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) is a common but often misunderstood illness that mostly affects women and is usually triggered by an infection. One of its main symptoms is feeling much worse after physical or mental effort. Many patients say their symptoms are not taken seriously.
In this large genetic study involving over 21,000 people with ME/CFS, researchers found eight genetic regions linked to the illness. Some of these genes are involved in how the body responds to infections. They also found links to nerve and immune system functions, but no connection to anxiety or depression.
This research helps confirm that ME/CFS is a real, biological illness and may lead to better understanding and treatment in the future. View Abstract
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Metabolic adaptation and fragility in healthy 3-D in vitro skeletal muscle tissues exposed to Chronic Fatigue Syndrome and Long COVID-19 sera.
“We propose that skeletal muscle tissue in ME/CFS and Long COVID-19 progresses through a hypermetabolic state, leading to severe muscular and mitochondrial deterioration. This is the first study to suggest such transient metabolic adaptation.”
Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS
Summary:
This study looked at the blood of ME/CFS patients before and after exercise and found several biological differences compared to healthy people. These included problems with how their bodies produce energy, signs of inflammation, immune system overreactions, gut issues, and stress on their cells. These problems got worse after exercise and were linked to how bad their symptoms were. The research could help lead to better treatments in the future. View Abstract
Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis
Summary:
In this study, researchers used a powerful artificial intelligence tool called HEAL2 to analyse the complete genetic data of people with ME/CFS. They identified 115 genes linked to the illness, many of which affect the brain and immune system. These genes were found to be less active in ME/CFS patients, especially in certain immune cells.
The study also found genetic links between ME/CFS and long COVID. This research could lead to better ways to diagnose ME/CFS and find new treatment options. It also shows how AI can help uncover the causes of other complex diseases. View Abstract
AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome
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Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study
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Brainstem Reduction and Deformation in the 4th Ventricle Cerebellar Peduncles in Long COVID Patients: Insights into Neuroinflammatory Sequelae and “Broken Bridge Syndrome”
Summary:
The researchers saw shrinkage and damage in parts of the brainstem and cerebellum, which were linked to patients’ symptoms like trouble walking, dizziness, and disrupted sleep. These brain changes may also explain some of the immune system overactivity seen in Long COVID, including the presence of harmful autoantibodies (antibodies that mistakenly attack the body).
The study supports the idea that Long COVID symptoms may come from a “disconnect” between brain regions and long-term overstimulation of stress and immune systems in the body. More research is needed to better understand what’s happening in the brain and how to treat it. View Abstract
2024
Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome
Related Article
571P Muscular metabolic plasticity in 3D in vitro models against systemic stress factors in ME/CFS and long COVID-19
https://www.sciencedirect.com/science/article/pii/S0960896624003353
Physical and cognitive stressors exacerbate symptoms in long COVID: more evidence triggering new research and therapeutic needs
https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00276-X/fulltext
Full text to the above study here.
Full text to the above study here.
Full text to the above study here.
Full text to the above study here.
Full text to the above study here.
“Presently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status.”
Full text to the above study here.
Full text to the above study here.
The paper above reports significant reductions in the functional connectivity between the brainstem and cerebellum regions of ME/CFS patients compared with healthy controls.
The above study suggest that deficiency of vasopressin secretion is a fundamental measurable part of the disease mechanisms, which may underlie a number of symptoms in ME/CFS, including the common complaint of orthostatic intolerance. Full text to the above study here.
“Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.” Full text to the above study here.
The above study has been criticised by experts in the field for its small patient cohort, patient selection process, low methodology standards, peculiar analysis of the data and the unfortunate term “effort preference”.
2023
“This study took serum samples from ME/CFS patients with insomnia and healthy controls and injected them into connective tissue cells called fibroblasts from mice. The mice tissues injected with ME/CFS serum displayed disturbances in their circadian rhythms — suggesting that something in the serum was disrupting regular sleep schedules.” — Health Rising. Full text to the above study here.
Full text to the above study here.
Full text to the above study here.
Quote from above study, “Our data suggest that graded exercise therapy almost certainly would cause harm.”
Full text to the above study here.
2022
Full text to the above study here.
Full text to the above study here.
2020
2019
Full text to above study here.
2018
2017
2016
2015
2014
2013
2012
Quote from above study, “CFS patients exhibited two different abnormal responses to exercise. Some patients demonstrated abnormal increases in mRNA for sensory and adrenergic receptors and a cytokine, resulting in fatigue or pain. A second group demonstrated abnormal decreases in adrenergic α-2A receptor’s transcription. None of the normal patients in the study showed these responses, and the authors thus suggest that this finding has the potential of serving as a biomarker for the disease.”
Quote from above study, “The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.”
2011
Quote from above study, “The more patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the previous day.”
Quote from above study, “CFS patients exhibit “profound abnormality in bioenergetic function.” When they exercise at the level of normal people, they demonstrate increased intramuscular acidosis that does not decrease normally with repeated exercise. Compared to normal people, it also takes four times as long for their pH to return to baseline after exercise.”
2010
Quote from above study, “The results of this study suggest that PEM is both a real and an incapacitating condition for women with CFS and that their responses to exercise are distinctively different from those of sedentary controls.”
Quote from above study, “CFS patients displayed abnormalities in recovery of intramuscular pH, related to autonomic dysfunction, following exercise.”
Quote from above study, “Following exercise, complement C4a levels go up more in CFS patients than in healthy people.”
Quote from above study, “CFS patients had a higher increase in nitric oxide metabolites after exercise than did controls.”
Quote from above study, “CFS patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls, and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients.”
2009
The above study, “A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS”
Quote from above study, “Considering the fact that these findings are exemplary for ME/CFS patients and that GET may even be harmful, it means that many patients are maltreated by the Belgian CFS Centers.”
Quote from above study, “The physiological cost of walking was significantly greater for people with CFS compared with healthy subjects.”
Quote from above study, “The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.”
Quote from above study, “MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.”
2008
Full text for above study here.
2007
Full text to above study here.
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995 and Prior Studies
Full text for above study here.
1956
After the 1955 epidemic among staff at Royal Free Hospital in London, researchers published their observations in The Lancet, noting a “pattern of abnormalities in spinal cord fluid and brain ganglia in patients” (The Tangled Story of ME/CFS — 5:25min into video). Subsequently, ME has maintained its official classification as a neurological disease by the World Health Organization (WHO) since 1969 (ICD 10 G93.3).
“Hard to believe that patients with ME have been treated so poorly for decades, but they have, and the stirring story of their resilience and unwillingness to be forgotten is brilliantly portrayed in these videos. If you really want to know about the most serious health challenge facing our planet, one that still has not been recognized, be sure to watch these videos and then demand the change that is so desperately needed.”
– LEONARD JASON, PH.D. Professor of Psychology. Director, Center for Community Research, DePaul University, Chicago.
