Evidence browser

E2 ModerateCohortPEM not requiredObservational

Comparison of the symptom networks of long-COVID and chronic fatigue syndrome: From modularity to connectionism.

Hyland, Michael E, Antonacci, Yuri, Bacon, Alison M·Scandinavian journal of psychology·2024

This study compared how symptoms are connected to each other in long-COVID and ME/CFS patients, along with people who have other conditions like fibromyalgia and IBS. Researchers found that while long-COVID and ME/CFS are related conditions, their symptoms connect differently—ME/CFS symptoms form more separate clusters, whereas long-COVID symptoms are more tightly linked together. The study suggests that these conditions may work through a network-like system in the body rather than a single broken mechanism.

Risk of chronic fatigue syndrome after COVID-19: A retrospective cohort study of 3227281 patients.

Chen, Chih-Wei, Lee, Hsun-Hua, Chang, Shu-Hao et al.·Journal of infection and public health·2024

This study looked at over 6 million patient records to compare people who had COVID-19 with people who didn't. Researchers found that people who had COVID-19 were about 1.6 times more likely to develop chronic fatigue syndrome (CFS) afterward. The increased risk appeared in people of all ages, both sexes, and different racial backgrounds.

Long COVID Overlap

E2 ModerateCohortPEM requiredLongitudinal

Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM).

Lange, Gudrun, Lin, Jin-Mann S, Chen, Yang et al.·Frontiers in neuroscience·2024

This study tested cognitive function (thinking and memory skills) in 261 people with ME/CFS and 165 healthy people using a computer-based screening test. Researchers found that people with ME/CFS process information more slowly than healthy people, but their accuracy was similar. Importantly, a single intense exercise test did not make cognitive problems worse, though the full clinic visit itself did cause some cognitive decline in both groups.

E2 ModerateBehavioralPEM not requiredCross-Sectional

[The Significance of Chronic Fatigue in the Post-Covid Consultation and its Consequences for Outpatient Rehabilitation in the Context of Statutory Accident Insurance].

Dalichau, Stefan, Kordy, Henrike, Klüver, Janna et al.·Psychotherapie, Psychosomatik, medizinische Psychologie·2024

This study looked at 454 people (mostly women aged 40–60) who developed long-term fatigue after COVID-19. Nearly all of them reported severe tiredness, and over 73% also experienced brain fog. The fatigue lasted about 14–15 months on average and significantly affected their ability to work and enjoy daily life. The researchers recommend that treatment should focus on managing chronic fatigue similar to ME/CFS, using education and practical coping strategies rather than trying to 'cure' the condition.

E2 ModerateCohortPEM unclearLongitudinal

Muscle abnormalities worsen after post-exertional malaise in long COVID.

Appelman, Brent, Charlton, Braeden T, Goulding, Richie P et al.·Nature communications·2024

This study looked at muscle tissue changes in long COVID patients, particularly focusing on post-exertional malaise (PEM)—the worsening of fatigue and pain after activity. Researchers found that muscles in long COVID patients showed structural damage, metabolic problems, and unusual deposits that got worse after activity triggered PEM. These findings help explain why exertion makes symptoms worse in some long COVID patients.

Energy MetabolismPost-Exertional Malaise

Association of physical symptoms with accelerometer-measured movement behaviors and functional capacity in individuals with Long COVID.

Rosa-Souza, Francisco José, Freire, Yuri Alberto, Galliano, Leony Morgana et al.·Scientific reports·2024

This study looked at 102 people with Long COVID to understand how specific symptoms affect their ability to move and be physically active. Researchers used activity trackers to measure daily movement and tested how far people could walk and how quickly they could stand up from a chair. They found that fatigue and post-exertional malaise (feeling worse after activity) were linked to lower daily step counts, while shortness of breath was linked to poorer performance on physical tests.

E2 ModerateCohortPEM not requiredObservational

Mismatch between subjective and objective dysautonomia.

Novak, Peter, Systrom, David M, Marciano, Sadie P et al.·Scientific reports·2024

This study examined whether questionnaires that ask patients about autonomic symptoms (like dizziness, heart racing, or sweating problems) match what doctors find when they perform actual autonomic tests. Researchers studied over 2,600 patients and found a surprising disconnect: questionnaires and actual tests did not correlate with each other, meaning some patients reported severe symptoms but tested normally, while others had significant test abnormalities but reported few symptoms. This finding held true across many conditions, including ME/CFS, suggesting that questionnaires alone cannot reliably detect autonomic problems.

Autonomic Nervous System

Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients.

Ercoli, Giuseppe, Selway-Clarke, Hugh, Truijen, Dena et al.·Clinical & translational immunology·2024

This study compared how well people with rheumatoid arthritis (RA) and ME/CFS patients can fight off a common bacterial infection called Streptococcus pneumoniae. Researchers found that RA patients had weaker immune responses to this bacteria compared to ME/CFS patients, which may explain why RA patients get pneumonia more often. The study also looked at how a common RA treatment (rituximab, which depletes B cells) affected these immune responses.

Immune System

E2 ModerateCohortPEM not requiredCross-Sectional

Development and Validation of the Short Form (JAEN-10) of the Joint Assessment of Equilibrium and Neuromotor Status Scale (JAEN-20).

Peinado-Rubia, Ana Belén, Osuna-Pérez, María Catalina, Núñez-Fuentes, David et al.·Journal of functional morphology and kinesiology·2024

Researchers created a shorter version of a balance and movement test (JAEN-10) to measure physical problems in people with fibromyalgia. The new 10-question test works just as well as the original 20-question version but takes less time to complete, which is helpful for people who get tired easily. The test successfully identified people with fibromyalgia and those at risk of falling.

Autonomic Nervous System

E2 ModerateCohortPEM required

How Long Is Long COVID? Evaluation of Long-Term Health Status in Individuals Discharged from a Specialist Community Long COVID Service.

Bodey, Rochelle, Grimaldi, Jennifer, Tait, Hannah et al.·Journal of clinical medicine·2024

This study followed people who had received specialist care for long COVID and were then discharged from the service. Nearly 3 years after their initial COVID infection, most patients (90%) still had long COVID symptoms and hadn't returned to their normal health. About 4 in 10 of these patients also met the criteria for ME/CFS, suggesting long COVID can develop into a lasting condition similar to ME/CFS.

Identifying the mental health burden in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients in Switzerland: A pilot study.

König, Rahel Susanne, Paris, Daniel Henry, Sollberger, Marc et al.·Heliyon·2024

This Swiss study surveyed 169 ME/CFS patients to understand how the disease affects their mental health and well-being. The researchers found that most patients experience significant emotional challenges, including sadness, hopelessness, and concerning rates of suicidal thoughts, often because others don't believe or understand their illness. The study shows that ME/CFS creates serious mental health burdens beyond just physical symptoms, and patients urgently need better medical, psychological, and social support.

The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Jason, Leonard A, McGarrigle, William J, Vermeulen, Ruud C W·Journal of personalized medicine·2024

This study tested 193 people with ME/CFS using a tilt table test to check if they had problems with their autonomic nervous system (the system that controls heart rate and blood pressure). About one in three participants showed signs of orthostatic intolerance—a condition where the body struggles to maintain proper blood pressure and heart rate when standing. People with these problems reported worse sleep, more severe post-exertional malaise (exhaustion after activity), and greater physical limitations.

E2 ModerateCohortPEM not requiredCross-Sectional

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue.

Mouat, Isobel C, Zhu, Li, Aslan, Alperen et al.·Journal of inflammation (London, England)·2024

This study looked at whether Epstein-Barr virus (EBV), a common virus that stays dormant in most people's bodies, reactivates in stroke patients who experience severe fatigue. Researchers compared 44 stroke survivors—22 with high fatigue and 22 with low fatigue—and measured both the amount of active virus and antibodies against it in their blood. While they found that EBV reactivation happened equally in both groups, people with high fatigue showed unusual patterns in their immune response to the virus, suggesting their bodies may not be fighting EBV normally.

Immune System

["The idea of rehabilitation will have to be completely rethought for this illness" - Qualitative results of an online survey on patients' experiences with inpatient rehabilitation for post COVID-19 condition (long COVID)].

Hammer, Sabine, Schmidt, Julia, Conrad, Annett et al.·Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen·2024

German researchers asked 1,191 long COVID patients about their experiences with inpatient rehabilitation programs. About half reported their health got worse during rehabilitation, mainly from exercise programs that were too intense. The study found that standard rehabilitation designed for other illnesses often doesn't work for long COVID patients with post-exertional malaise, and programs should instead focus on teaching patients how to pace their activities safely.

Stroop task and practice effects demonstrate cognitive dysfunction in long COVID and myalgic encephalomyelitis / chronic fatigue syndrome.

Baraniuk, James N, Thapaliya, Kiran, Inderyas, Maira et al.·Scientific reports·2024

This study tested how quickly people with Long COVID and ME/CFS could complete a simple task involving reading color words displayed in different colored inks. Both patient groups were noticeably slower at this task than healthy people, and unlike healthy people, they didn't get faster with practice. This suggests that ME/CFS and Long COVID may involve a problem with how different parts of the brain communicate during problem-solving.

Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data.

Mudie, Kathleen, Ramiller, Allison, Whittaker, Sadie et al.·Frontiers in neurology·2024

This study looked at whether ME/CFS patients with loose, flexible joints (joint hypermobility) form a distinct group with different symptoms and health impacts. Researchers surveyed 815 ME/CFS patients and found that about 16% had joint hypermobility. These patients reported worse quality of life, more pain, and more symptoms affecting their nervous system, thinking, digestion, and muscles compared to ME/CFS patients without joint hypermobility.

Autonomic Nervous System

[Systems thinking, subjective findings and diagnostic "pigeonholing" in ME/CFS: A mainly qualitative public health study from a patient perspective].

Habermann-Horstmeier, Lotte, Horstmeier, Lukas Maximilian·Deutsche medizinische Wochenschrift (1946)·2024

This German study asked 544 ME/CFS patients about their experiences getting diagnosed and working with doctors. Patients reported that many doctors don't recognize ME/CFS as a real disease, instead dismissing it as purely psychological. The study found that poor diagnosis experiences and lack of doctor recognition of ME/CFS as a biological multisystem illness significantly damage the relationship between patients and their healthcare providers.

Diagnostics

Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan.

Morita, Satoru, Tokumasu, Kazuki, Otsuka, Yuki et al.·PloS one·2024

This study looked at 739 patients with long COVID to understand how many developed ME/CFS and what factors were involved. Researchers found that ME/CFS affected about 8% of long COVID patients, but the rate varied depending on which COVID variant caused the initial infection—it was much higher (24%) in early COVID but dropped significantly (3%) during the Omicron wave. Brain fog complaints increased over time, even as strict ME/CFS diagnoses became less common.

E2 ModerateCohortPEM not requiredCross-Sectional

Cognitive reserve as a protective factor against cognitive impairment in chronic fatigue syndrome.

Surendran, Gopika, Jose, Tony P·Applied neuropsychology. Adult·2024

This study examined whether people's life experiences and education—called 'cognitive reserve'—help protect them from the thinking and memory problems common in ME/CFS. Researchers tested 91 people with ME/CFS and found that those with more cognitive reserve had fewer cognitive problems. The severity of someone's ME/CFS was the main factor affecting both cognitive reserve and cognitive problems, rather than age or gender.

E2 ModerateGuidelinePEM unclearGuideline

Practical Recommendations for Exercise Training in Patients with Long COVID with or without Post-exertional Malaise: A Best Practice Proposal.

Gloeckl, Rainer, Zwick, Ralf H, Fürlinger, Ulrich et al.·Sports medicine - open·2024

This study created practical guidelines for exercise training in people with long COVID, especially those who experience post-exertional malaise (PEM)—when symptoms get worse after physical activity. The researchers reviewed 46 previous studies and surveyed 14 international experts to develop three different exercise approaches depending on whether someone has no PEM, mild/moderate PEM, or severe PEM. These guidelines aim to help healthcare professionals safely design exercise programs tailored to each person's specific situation.