Evidence browser

E2 ModerateCohortPEM unclearCase-Control

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Jonsjö, Martin A, Åström, Jenny, Jones, Michael P et al.·Brain, behavior, & immunity - health·2020

This study compared how 'sick' people with ME/CFS and chronic pain feel compared to other groups. Researchers found that ME/CFS and chronic pain patients reported feeling as sick as healthy people who were given a bacterial toxin to trigger temporary inflammation. These high levels of sickness feelings were similar across both conditions and higher than what primary care patients reported, suggesting that the persistent sickness sensation in ME/CFS and chronic pain may involve similar biological mechanisms related to inflammation and how the brain processes illness signals.

Immune System

Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome.

Shikova, Evelina, Reshkova, Valentina, Kumanova, Аntoniya et al.·Journal of medical virology·2020

Researchers tested 58 ME/CFS patients and 50 healthy people for three common viruses (EBV, CMV, and HHV-6) that have been suspected of triggering ME/CFS. They found that ME/CFS patients had significantly higher rates of active EBV infection in their bloodstream compared to healthy people, though most people in both groups carried these viruses in a dormant state. This suggests that for some patients, active EBV infection may play a role in ME/CFS development.

Immune System

E2 ModerateBehavioralPEM unclearCross-Sectional

Prevalence and treatment of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and co-morbid severe health anxiety.

Daniels, Jo, Parker, Hannah, Salkovskis, Paul Martin·International journal of clinical and health psychology : IJCHP·2020

This study found that about 42% of people with ME/CFS also experience significant health anxiety—excessive worry about their health and symptoms. When people have both ME/CFS and health anxiety together, they tend to report worse fatigue and more difficulty with physical activities. The researchers tested whether cognitive behavioral therapy (a type of talking therapy) could help reduce health anxiety in ME/CFS patients, and found it produced meaningful improvements.

E2 ModerateCohortPEM not requiredCross-Sectional

The presence of overlapping quality of life symptoms in primary antibody deficiency (PAD) and chronic fatigue syndrome (CFS).

Bansal, Rhea A, Tadros, Susan, Bansal, Amolak S·Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology·2020

This study looked at whether people with primary antibody deficiency (PAD)—a condition where the immune system doesn't make enough protective proteins—also experience ME/CFS-like symptoms. Researchers sent questionnaires to over 680 PAD patients and found that about 16% of those who responded had symptoms matching ME/CFS criteria, which is much higher than the general population. The study also found that sleep problems, fatigue, anxiety, and low mood were very common in PAD patients.

Sleep

E2 ModerateCohortPEM unclearObservational

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study.

Rekeland, Ingrid G, Fosså, Alexander, Lande, Asgeir et al.·Frontiers in medicine·2020

Researchers tested whether cyclophosphamide, a chemotherapy drug, could help people with ME/CFS based on observations that some patients improved after cancer treatment. Forty patients received six infusions of this drug over six months, with check-ins lasting up to four years. More than half the patients reported meaningful improvements in fatigue and physical activity, with many staying better even years later.

Interventions

E2 ModerateCohortPEM unclearCase-Control

Accurate and objective determination of myalgic encephalomyelitis/chronic fatigue syndrome disease severity with a wearable sensor.

Palombo, Turner, Campos, Andrea, Vernon, Suzanne D et al.·Journal of translational medicine·2020

Researchers developed a wearable sensor that measures how much time ME/CFS patients spend standing or walking each day (called UpTime). In a small study of 15 people, they found that severely ill ME/CFS patients spend less than 20% of their day upright, moderately ill patients spend 20-30%, while healthy people spend more than 30%. This sensor measurement was more accurate than asking patients to estimate their activity themselves, suggesting it could be a reliable way to track disease severity and test new treatments.

Prediction of Discontinuation of Structured Exercise Programme in Chronic Fatigue Syndrome Patients.

Kujawski, Sławomir, Cossington, Jo, Słomko, Joanna et al.·Journal of clinical medicine·2020

This study looked at why some people with ME/CFS could complete a gradual exercise programme while others had to stop. Researchers measured several body functions—like nervous system activity, reaction time, and heart rate—before the programme started. They found that people whose bodies showed higher stress responses and slower reaction times were more likely to drop out of the exercise programme.

E2 ModerateCohortPEM unclearCase-Control

Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions.

Helliwell, A M, Sweetman, E C, Stockwell, P A et al.·Clinical epigenetics·2020

This study looked at chemical tags on DNA called methylation patterns in people with ME/CFS compared to healthy people. These tags can turn genes on or off without changing the DNA itself. Researchers found that people with ME/CFS have different methylation patterns, particularly in genes related to energy production, immune function, and brain chemistry, which may help explain why they experience the symptoms they do.

Energy MetabolismImmune System

BiomarkersPost-Exertional Malaise

Machine Learning Detects Pattern of Differences in Functional Magnetic Resonance Imaging (fMRI) Data between Chronic Fatigue Syndrome (CFS) and Gulf War Illness (GWI).

Provenzano, Destie, Washington, Stuart D, Rao, Yuan J et al.·Brain sciences·2020

This study used brain imaging (fMRI) and computer learning programs to see if people with ME/CFS and Gulf War Illness have different patterns of brain activity during memory tasks, both before and after exercise. Researchers found that computer programs could correctly distinguish between the two conditions about 75-82% of the time, and identified about 30-33 brain regions that showed different activation patterns between the two groups. This suggests that ME/CFS and Gulf War Illness may have measurable biological differences in how the brain works during cognitive tasks and recovery from exertion.

E2 ModerateCohortPEM not requiredCross-Sectional

Self-reported cognitive impairment in individuals with Primary Immunodeficiency Disease.

Sowers, Kerri L, Gayda-Chelder, Christine A, Galantino, Mary Lou·Brain, behavior, & immunity - health·2020

This study looked at whether people with Primary Immunodeficiency Disease (PID)—a condition where the immune system doesn't work properly—experience brain fog or memory problems. Researchers asked 292 people with PID to fill out surveys about their memory, mood, and anxiety. They found that people with PID reported significantly more memory problems and higher levels of anxiety and depression compared to people without these conditions.

Cognitive Impairment

E2 ModerateBehavioralPEM not requiredCase-Control

A MAPP Network Case-control Study of Urological Chronic Pelvic Pain Compared With Nonurological Pain Conditions.

Afari, Niloofar, Buchwald, Dedra, Clauw, Daniel et al.·The Clinical journal of pain·2020

This study compared people with chronic pelvic pain conditions to people with other widespread chronic pain conditions like fibromyalgia and chronic fatigue syndrome, as well as healthy volunteers. Researchers found that while these conditions affect different parts of the body, people with all these conditions share similar emotional and psychological challenges—like anxiety, depression, and stress—suggesting they may share common underlying causes. The study suggests that treating these conditions effectively may require addressing both physical pain and psychological factors together.

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome.

Scherbakov, Nadja, Szklarski, Marvin, Hartwig, Jelka et al.·ESC heart failure·2020

This study looked at blood vessel function in people with ME/CFS by measuring how well small arteries in the arm respond to increased blood flow. Researchers found that about half of ME/CFS patients had abnormal blood vessel responses, compared to only 20% of healthy people. People with this blood vessel problem reported more severe fatigue, more frequent need for rest breaks, and worse immune-related symptoms like sore throat and swollen lymph nodes.

Immune System

Energy MetabolismImmune System

Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population.

Kitami, Toshimori, Fukuda, Sanae, Kato, Tamotsu et al.·Scientific reports·2020

Researchers studied 48 ME/CFS patients and 52 healthy people in Japan to find biological markers of the disease. They tested blood samples, gut bacteria, immune cells, and sleep patterns, identifying 26 potential markers that differ between patients and healthy people. Three markers stood out as most important: certain types of white blood cells, gut bacteria composition, and fat-like molecules in the blood, which were especially linked to sleep problems in ME/CFS patients.

E2 ModerateBehavioralPEM not requiredObservational

Hospital Records of Pain, Fatigue, or Circulatory Symptoms in Girls Exposed to Human Papillomavirus Vaccination: Cohort, Self-Controlled Case Series, and Population Time Trend Studies.

Thomsen, Reimar Wernich, Öztürk, Buket, Pedersen, Lars et al.·American journal of epidemiology·2020

This large Danish study looked at whether the HPV vaccine (which prevents cervical cancer) was linked to symptoms like pain, fatigue, or heart problems in girls. Researchers compared vaccinated and unvaccinated girls over 14 years and found no increase in hospital visits for these symptoms in vaccinated girls. The symptoms they tracked increased over time in both vaccinated and unvaccinated children, suggesting other factors were responsible.

Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: outcomes from a specialist clinic in the UK.

Adamson, James, Ali, Sheila, Santhouse, Alastair et al.·Journal of the Royal Society of Medicine·2020

This study looked at whether cognitive behavioural therapy (CBT)—a type of talk therapy focused on changing thoughts and behaviors—helps people with ME/CFS feel better in a real-world clinic setting. Researchers tracked nearly 1,000 patients receiving CBT and found that most improved in fatigue, physical functioning, and social life, with 85% reporting they felt better and 90% satisfied with treatment.

Interventions

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome.

Fatt, Scott J, Beilharz, Jessica E, Joubert, Michael et al.·Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine·2020

This study found that people with ME/CFS have reduced calming nervous system activity during deep sleep, compared to healthy people. This overactive state during sleep—even when the brain should be resting—is linked to poor sleep quality and feeling unwell. The findings suggest that the body's inability to fully relax during sleep may be a key problem in ME/CFS.

E2 ModerateCohortPEM not requiredCase-Control

Sleep problems in adolescents with CFS: A case-control study nested within a prospective clinical cohort.

Loades, Maria Elizabeth, Rimes, Katharine A, Chalder, Trudie·Clinical child psychology and psychiatry·2020

This study looked at sleep problems in teenagers with ME/CFS compared to healthy teenagers and those with asthma. Teenagers with ME/CFS reported significantly more sleep difficulties than both comparison groups. When researchers checked in 3 months later without any treatment, sleep problems remained largely unchanged, suggesting that sleep issues in ME/CFS don't improve on their own and may need specific attention during treatment.

Sleep

Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis.

Hviid, Anders, Thorsen, Nicklas M, Valentiner-Branth, Palle et al.·BMJ (Clinical research ed.)·2020

This study examined whether the HPV vaccine (used to prevent cervical cancer) was linked to ME/CFS, complex regional pain syndrome, or POTS in over 1.3 million Danish girls and women. Researchers found no evidence that the vaccine caused these conditions—the rates of these illnesses were similar whether or not girls received the vaccine.

E2 ModerateCohortPEM not requiredCross-Sectional

Functional gastrointestinal disorders are increased in joint hypermobility-related disorders with concomitant postural orthostatic tachycardia syndrome.

Tai, Foong Way David, Palsson, Olafur S, Lam, Ching Y et al.·Neurogastroenterology and motility·2020

This study looked at people with joint hypermobility disorders (including Ehlers-Danlos syndrome) to understand how often they experience stomach and digestive problems. The researchers found that those who also have POTS (a condition affecting heart rate and blood pressure when standing) had significantly more digestive issues than those without POTS. The digestive problems remained worse in the POTS group even after accounting for other conditions like chronic fatigue syndrome.