Evidence browser

E2 ModerateDiagnosticPEM unclearMethods-Paper

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.

Cognitive Impairment

Optimizing Exclusion Criteria for Clinical Trials of Persistent Lyme Disease Using Real-World Data.

Johnson, Lorraine, Shapiro, Mira, Needell, Deanna et al.·Healthcare (Basel, Switzerland)·2024

This study looked at the rules that researchers use to decide who can join clinical trials for persistent Lyme disease (PLD). The researchers found that current rules exclude about 90% of patients, making it very hard to find enough people for studies. By relaxing some of these rules—especially those that exclude people with coexisting conditions like fibromyalgia or fatigue—researchers could include many more patients (up to 64%) while still conducting valid research.

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.

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.

Fonseca, André, Szysz, Mateusz, Ly, Hoang Thien et al.·Medicina (Kaunas, Lithuania)·2024

Researchers examined immune responses (antibodies) against Epstein-Barr virus in ME/CFS patients to see if these could be used to diagnose the condition. They found that a specific set of 26 antibodies could reliably identify ME/CFS patients whose illness started after an infection, but these antibodies don't appear to explain why the autoimmune problems occur. The findings suggest that while these antibodies might be useful for diagnosis in some patients, they may not be the root cause of ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome.

Bizjak, Daniel Alexander, Ohmayer, Birgit, Buhl, Jasmine Leonike et al.·International journal of molecular sciences·2024

This study examined the energy-producing structures (mitochondria) inside muscle cells of people with ME/CFS and long COVID, comparing them to healthy people. Researchers found that mitochondria in both conditions work less efficiently and have structural damage, but the patterns differ: long COVID shows more damage to a specific energy-producing pathway, while ME/CFS shows more overall structural wear and tear in the mitochondria themselves.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact on Quality of Life (QoL) of Persons with ME/CFS.

Muirhead, Nina L, Vyas, Jui, Ephgrave, Rachel et al.·Medicina (Kaunas, Lithuania)·2024

This study surveyed 876 people with ME/CFS from 26 countries to understand how the condition affects their daily lives. People with ME/CFS reported very poor quality of life, with an average health rating of 36 out of 100. The most common problems were difficulty doing everyday activities (97%), pain (92%), and trouble with movement (83%).

Pain and Sensitization

E2 ModerateCohortPEM requiredCross-Sectional

Comparison of T-cell receptor diversity of people with myalgic encephalomyelitis versus controls.

Dibble, Joshua J, Ferneyhough, Ben, Roddis, Matthew et al.·BMC research notes·2024

Researchers studied immune cells called T-cells in people with ME/CFS to see if they were different from those in healthy people. They looked at genetic patterns in blood samples from 40 people in each group: those severely affected by ME/CFS, those mildly or moderately affected, people with multiple sclerosis, and healthy controls. Although they used advanced technology and computer programs to analyze the data, they found that the T-cell patterns were not notably different between the groups.

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

Overlapping conditions in Long COVID at a multisite academic center.

Grach, Stephanie L, Dudenkov, Daniel V, Pollack, Beth et al.·Frontiers in neurology·2024

This study looked at 247 patients with Long COVID who visited Mayo Clinic to see what new health problems developed after their COVID-19 infection. Researchers compared them to 40 people who had COVID-19 but recovered normally. The results showed that Long COVID patients experienced much higher rates of pain, neurological symptoms, sleep problems, and other issues. Importantly, 58% of Long COVID patients screened positive for ME/CFS—a serious fatigue and post-exertional symptom condition—compared to none of the control group.

Sleep

["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.

E2 ModerateCohortPEM requiredObservational

Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations.

Keller, Betsy, Receno, Candace N, Franconi, Carl J et al.·Journal of translational medicine·2024

This study tested 84 people with ME/CFS and 71 healthy controls on an exercise bike on two days, 24 hours apart. People with ME/CFS performed worse on the second day of testing—their oxygen use, heart rate, and exercise capacity all declined—while healthy people stayed about the same. This objective decline mirrors the real-world experience of post-exertional malaise, where ME/CFS patients feel worse after physical activity.

E2 ModerateCohortPEM requiredCross-Sectional

Impaired Hand Grip Strength Correlates with Greater Disability and Symptom Severity in Post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Paffrath, Anna, Kim, Laura, Kedor, Claudia et al.·Journal of clinical medicine·2024

Researchers tested hand grip strength in 144 women with long-COVID symptoms, comparing those who met strict ME/CFS criteria (78 patients) with those who had other long-COVID symptoms. People with ME/CFS showed weaker grip strength and more severe disability, fatigue, and symptom worsening after activity compared to other long-COVID patients. Weak grip strength appeared to be connected to the core symptoms that define ME/CFS, suggesting muscle weakness in ME/CFS may share a common cause with other hallmark symptoms.

E2 ModerateCohortPEM unclearLongitudinal

Association Between Chronic Pain and Fatigue Severity with Weather and Air Pollution Among Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Jones, Chloe Lisette, Haskin, Olivia, Younger, Jarred Wayne·International journal of environmental research and public health·2024

This study looked at whether weather and air quality affect pain and fatigue in women with ME/CFS. Fifty-eight women tracked their daily pain and fatigue levels for about 2 months while researchers compared their symptoms to local weather and air pollution data. The results showed that worse air quality, lower wind speeds, and higher levels of certain pollutants were linked to days when patients experienced more pain and fatigue.

Prevalence and determinants of post-acute sequelae after SARS-CoV-2 infection (Long COVID) among adults in Mexico during 2022: a retrospective analysis of nationally representative data.

Bello-Chavolla, Omar Yaxmehen, Fermín-Martínez, Carlos A, Ramírez-García, Daniel et al.·Lancet regional health. Americas·2024

This study looked at how many adults in Mexico experienced long-lasting symptoms after COVID-19 infection in 2022. Researchers found that about 1 in 5 people who had COVID-19 reported ongoing problems like fatigue, muscle pain, brain fog, and loss of taste or smell. The study showed that people who caught COVID-19 multiple times, had depression, or lived in poorer areas were more likely to develop these long-term symptoms, while vaccination and infection with newer variants reduced risk.

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.

E2 ModerateCohortPEM not required

The influence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) family history on patients with ME/CFS.

Jason, Leonard A, Ngonmedje, Sarah·Exploration of medicine·2024

This study looked at whether ME/CFS runs in families and if people with ME/CFS who have a family history of the disease are different from those without it. Researchers compared 400 ME/CFS patients with 414 people who had other chronic illnesses like multiple sclerosis or post-polio syndrome. They found that ME/CFS is much more common in families (18% of ME/CFS patients had relatives with ME/CFS) compared to the control groups (3.9%), and those with a family history of ME/CFS were more likely to experience stomach and digestive problems.

Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.

Elahi, Shokrollah, Rezaeifar, Maryam, Osman, Mohammed et al.·Frontiers in immunology·2024

Researchers studied two proteins in the blood—galectin-9 and artemin—to see if they could help identify people with Long COVID who also have ME/CFS. They found that galectin-9 levels were higher in Long COVID patients and were linked to inflammation and thinking problems. These proteins may help doctors distinguish Long COVID with ME/CFS from people who recovered normally from COVID-19.

E2 ModerateCohortPEM unclearObservational

Resonant breathing improves self-reported symptoms and wellbeing in people with Long COVID.

Polizzi, Jessica, Tosto-Mancuso, Jenna, Tabacof, Laura et al.·Frontiers in rehabilitation sciences·2024

This study looked at whether slow, controlled breathing (called resonant breathing) could help people with Long COVID feel better. Ninety-nine people with Long COVID tried a resonant breathing program and reported their symptoms before and after. Most people said they felt better overall, especially in areas like stress control, focus, breathing ability, and sleep quality.