Evidence browser

E2 ModerateCohortPEM not requiredLongitudinal

Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome.

Barletta, Maria Angela, Marino, Gerardo, Spagnolo, Barbara et al.·Clinical and experimental medicine·2023

This study tested whether a combination of two supplements—coenzyme Q10 and alpha lipoic acid—could help people with chronic COVID syndrome who experience fatigue, muscle pain, and sleep problems. Researchers compared 116 people who took these supplements with 58 people who received no treatment. More than half of the people taking the supplements saw significant improvement in their fatigue, while only a small percentage of the untreated group improved.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

Spatz, Erica S, Gottlieb, Michael, Wisk, Lauren E et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2023

This study followed adults who tested positive or negative for COVID-19 and tracked their symptoms over three months. At the three-month mark, people who had COVID-19 were much more likely to still have symptoms like fatigue, breathing problems, or muscle pain compared to those who tested negative. Importantly, symptoms of post-infectious syndromes (like unrefreshing sleep and fatigue) were common in both groups, suggesting these symptoms can occur even without COVID-19 infection.

Long COVID Overlap

E2 ModerateCohortPEM requiredCross-Sectional

A Quick and Practical Approach to Secure a Chronic Fatigue Syndrome Diagnosis: The Novel Functional Limitation Index.

Corbalán, Juan Antonio, Feltes, Gisela, Silva, Daniela et al.·Journal of clinical medicine·2023

Researchers developed a simple test called the Functional Limitation Index (FLI) to help doctors diagnose ME/CFS more quickly and objectively. The test uses measurements from exercise testing and breathing tests to identify how much a person's physical function is impaired. In their study, the FLI successfully distinguished ME/CFS patients from healthy people and athletes with high accuracy.

Diagnostics

Focus on post-exertional malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deterioration.

Wormgoor, Marjon E A, Rodenburg, Sanne C·Frontiers in neurology·2023

This study looked at whether ME/CFS specialists in Norway were paying attention to post-exertional malaise (PEM)—the worsening of symptoms after physical or mental effort, which is a key feature of ME/CFS. They surveyed nearly 900 patients about their experiences in specialist clinics and hospitals. The results showed that when doctors focused on PEM and helped patients avoid overexertion, patients felt better, were more satisfied with their care, and were less likely to get worse after treatment.

E2 ModerateCohortPEM not requiredLongitudinal

Tai Chi increases functional connectivity and decreases chronic fatigue syndrome: A pilot intervention study with machine learning and fMRI analysis.

Wu, Kang, Li, Yuanyuan, Zou, Yihuai et al.·PloS one·2022

This study tested whether Tai Chi exercise could help people with ME/CFS by looking at brain activity patterns. Researchers compared 20 ME/CFS patients with 20 healthy people, teaching both groups Tai Chi for one month. They found that Tai Chi improved fatigue, sleep quality, and overall health, and that specific brain networks became better connected after the training.

Sleep

Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety, and chronic fatigue syndrome-like symptoms due to COVID-19: A nomothetic network approach.

Al-Jassas, Hawraa Kadhem, Al-Hakeim, Hussein Kadhem, Maes, Michael·Journal of affective disorders·2022

This study examined 60 COVID-19 patients and 30 healthy controls to understand why some people develop depression, anxiety, and fatigue-like symptoms after COVID-19 infection. The researchers found that lung damage (seen on CT scans), low oxygen levels, and an overactive immune response are connected to these mental health and fatigue symptoms. Essentially, the physical damage to the lungs may trigger immune system activation, which then leads to depression, anxiety, and fatigue.

Immune System

Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study.

Chudzik, Michał, Lewek, Joanna, Kapusta, Joanna et al.·Journal of clinical medicine·2022

This study followed 488 people without serious health conditions after they recovered from COVID-19 to see who developed Long COVID symptoms. Researchers found that people who had a severe acute COVID-19 illness, higher body weight, and joint pain during their initial infection were more likely to develop Long COVID. About 45% of those who developed Long COVID had symptoms that persisted beyond the follow-up period.

Long COVID Overlap

E2 ModerateCohortPEM unclearObservational

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

O'Neal, Adam J, Glass, Katherine A, Emig, Christopher J et al.·Proteomes·2022

Researchers tested blood samples from ME/CFS patients to look for antibodies against 122 different germs that might trigger the illness. They compared the results to healthy people of similar age, sex, and weight. While they found differences in how men and women with ME/CFS respond to infections, they couldn't identify one specific germ as the culprit.

Immune System

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection.

Bileviciute-Ljungar, Indre, Norrefalk, Jan-Rickard, Borg, Kristian·Journal of clinical medicine·2022

This study looked at 100 people who had mild COVID-19 but developed long-lasting symptoms afterward. Researchers asked about their pain, fatigue, sleep problems, and quality of life. Three-quarters of the participants reported widespread pain in various parts of their body, and many showed signs of fibromyalgia. The study found that pain is a major problem for people with long COVID and needs better treatment.

E2 ModerateCohortPEM requiredCross-Sectional

Alteration of Cortical Volume and Thickness in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Staines, Donald et al.·Frontiers in neuroscience·2022

Researchers used brain imaging to compare the brains of people with ME/CFS to healthy people. They found that people with ME/CFS had some areas of the brain that were thinner and other areas that were larger, particularly in regions involved in thinking and emotion. These brain differences were also connected to how severe symptoms like fatigue, sleep problems, and cognitive difficulties were in each person.

Cognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Small-Fiber Polyneuropathy Is Prevalent in Patients With Interstitial Cystitis/Bladder Pain Syndrome.

Wolff, Dylan T, Xu, Raymond, Overholt, Tyler et al.·Urogynecology (Philadelphia, Pa.)·2022

Researchers found that about one-third of people with bladder pain syndrome (IC/BPS) have small-fiber polyneuropathy (SFPN), a condition where tiny nerves in the skin are damaged or reduced. Notably, people with SFPN were significantly more likely to also have chronic fatigue syndrome (31% vs 10.6%). This suggests these two painful conditions may share a common nerve-related mechanism.

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology.

Danilenko, Olga V, Gavrilova, Natalia Y, Churilov, Leonid P·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study found that ME/CFS patients have unusual immune system patterns—specifically, their bodies produce antibodies (immune proteins) that attack their own nervous system tissues. The researchers divided ME/CFS patients into three groups based on cause (viral infection, stress, or unknown origin) and found that different groups had different patterns of these self-attacking antibodies. Importantly, all ME/CFS patients showed elevated levels of antibodies against brain and nerve proteins, which could explain why the illness affects multiple body systems.

Immune System

E2 ModerateBehavioralPEM not requiredCross-Sectional

The psychological features of distinct somatic syndromes: A cluster analysis according to population-based somatic symptom profiles in Taiwan.

Huang, Wei-Lieh, Chang, Shu-Sen, Liao, Shih-Cheng·Journal of the Formosan Medical Association = Taiwan yi zhi·2022

This study looked at whether different types of physical symptoms (like fatigue, pain, digestive problems, and heart-related symptoms) represent separate conditions or are all part of one bigger syndrome. Researchers analyzed survey data from 550 people in Taiwan and found that people tend to cluster into four different groups based on their symptom patterns, and each group had different levels of depression, anxiety, and health worry.

E2 ModerateCohortPEM not requiredLongitudinal

Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection.

Sandler, Carolina X, Cvejic, Erin, Valencia, Braulio M et al.·Frontiers in neurology·2022

This study followed people who had acute viral infections (EBV, Ross River virus, or Q fever) to see who developed ME/CFS-like symptoms by 6 months. About 1 in 5 participants met CFS criteria. The researchers found that people who felt more severely ill during their acute infection, and those with mood problems during that time, were more likely to have prolonged fatigue and continued mood difficulties afterward.

Cerebral gray matter volume correlates with fatigue and varies between desk workers and non-desk workers.

Putra, Handityo A, Park, Kaechang, Yamashita, Fumio et al.·Frontiers in behavioral neuroscience·2022

This study looked at how fatigue is connected to the size of different brain regions in 1,618 healthy people. Researchers found that people who reported more fatigue had smaller volume in one brain area (supplementary motor area) but larger volume in two other areas (superior parietal lobule and basal forebrain). Interestingly, desk workers and non-desk workers showed different patterns, suggesting that work environment may influence how fatigue affects the brain.

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

Donnachie, Ewan, Hapfelmeier, Alexander, Linde, Klaus et al.·BMJ open·2022

This study looked at health insurance records from nearly 400,000 people in Germany who had COVID-19 to see how many developed long COVID symptoms lasting at least 12 weeks. About 14% of COVID-19 patients received a diagnosis of post-COVID syndrome, with the most common symptoms being fatigue, breathing problems, and loss of taste or smell. These symptoms occurred much more often in COVID-19 patients compared to people who had other respiratory infections or no respiratory illness.

Cognitive Impairment

Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults.

Havdal, Lise Beier, Berven, Lise Lund, Selvakumar, Joel et al.·Frontiers in neurology·2022

This study looked at young people (ages 12-25) who had COVID-19 but were not hospitalized, comparing them to people who didn't have COVID-19. Researchers found that COVID-19 patients reported more fatigue and post-exertional malaise (PEM)—a worsening of symptoms after physical activity—and had slightly elevated markers of brain injury in their blood. However, their thinking and memory abilities tested normally, and the blood markers didn't directly correlate with their symptoms.

E2 ModerateCohortPEM unclearCross-Sectional

The Assessment of Fatigue in Rheumatoid Arthritis Patients and Its Impact on Their Quality of Life.

Dar, Waseem R, Mir, Irfan A, Siddiq, Summra et al.·Clinics and practice·2022

This study looked at fatigue in people with rheumatoid arthritis (RA), an autoimmune disease that causes joint pain and inflammation. Researchers found that fatigue was very common and severely affected quality of life in RA patients, even when their inflammation was being treated. The study suggests that doctors often focus on treating joint inflammation but may overlook how much fatigue impacts their patients' daily lives.

Long-term sequelae of COVID-19 (myalgic encephalomyelitis): An international cross-sectional study.

Shaheen, Nour, Shaheen, Ahmed·Medicine·2022

This study examined how COVID-19 affects people's health long after the initial infection, including whether some people develop ME/CFS (myalgic encephalomyelitis) as a result. Researchers planned to survey 20,000 people worldwide about their ongoing symptoms weeks to months after COVID-19 infection, using detailed questionnaires to capture a wide range of both common and unusual long-term effects. The goal was to understand who develops long-term problems and whether COVID-19 can trigger ME/CFS in previously healthy people.