Evidence browser

COVID-19: Post-recovery Manifestations.

Shaikh, Safia, Siddiqi, Zunaira, Ukachukwu, Crystal et al.·Cureus·2023

This study asked nearly 200 people recovering from COVID-19 about their symptoms. Most patients (85%) reported ongoing problems after infection, with fatigue being the most common complaint (59%). Other frequent problems included reduced physical stamina (49%), shortness of breath (33%), and anxiety (24%). The symptoms resembled those seen in ME/CFS, though the study did not confirm a direct connection.

E2 ModerateCohortPEM unclearLongitudinal

Free-water-corrected diffusion and adrenergic/muscarinic antibodies in myalgic encephalomyelitis/chronic fatigue syndrome.

Kimura, Yukio, Sato, Wakiro, Maikusa, Norihide et al.·Journal of neuroimaging : official journal of the American Society of Neuroimaging·2023

Researchers used a specialized brain imaging technique to look for signs of inflammation in the brains of ME/CFS patients and compared these findings to levels of harmful antibodies (immune proteins) in their blood. They found that certain antibodies were linked to visible changes in a specific brain region called the right frontal operculum, and that longer disease duration was associated with more brain changes. These findings suggest that ME/CFS may involve both immune system dysfunction and measurable changes in brain structure.

Neuroinflammation

Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue.

Palacios, Natalia, Molsberry, Samantha, Fitzgerald, Kathryn C et al.·Scientific reports·2023

This study examined whether ME/CFS is simply an extreme version of regular fatigue, or if it's a fundamentally different condition. Researchers surveyed over 41,000 nurses and found that ME/CFS and severe fatigue have different risk factors—meaning different things cause them. This suggests that ME/CFS is a distinct condition with its own underlying biology, not just 'really bad tiredness.'

Diagnostics

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.

Bonilla, Hector, Quach, Tom C, Tiwari, Anushri et al.·Frontiers in neurology·2023

This study looked at 140 people suffering from long COVID symptoms and found that nearly half of them (43%) met the medical criteria for ME/CFS. Most patients had severe fatigue, brain fog, and unrefreshing sleep that lasted around 9-10 months on average. People with higher body weight and greater functional decline were more likely to develop the ME/CFS form of long COVID.

E2 ModerateCohortPEM not requiredCross-Sectional

Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary.

Johnson, Madeline, Torres, Chelsea, Watts-Rich, Halli et al.·Work (Reading, Mass.)·2023

This study asked adults with ME/CFS about whether they experienced symptoms during childhood. Researchers analyzed comments from patients on a popular blog forum and found that about 43% of adults reported having ME/CFS before age 18. The study identified common themes in patients' stories, including mental health struggles, family history of illness, feeling misunderstood by others, and difficulties at school.

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to Long COVID: A precision nomothetic approach.

Al-Hadrawi, Dhurgham Shihab, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F et al.·Acta neuropsychiatrica·2023

This study examined whether low oxygen levels and high fever during acute COVID-19 could predict who develops Long COVID symptoms like fatigue, depression, and anxiety. Researchers found that these two early warning signs, combined with being female, could explain about 61% of why some people develop these lingering symptoms. They also identified a subgroup (about 27% of Long COVID patients) with particularly severe oxygen drops and fever who experienced the worst combination of fatigue, mood problems, and digestive symptoms.

Long COVID Overlap

E2 ModerateCohortPEM unclearObservational

Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation.

Cambras, Trinitat, Zerón-Rugerio, Maria Fernanda, Díez-Noguera, Antoni et al.·International journal of molecular sciences·2023

This study looked at how the bodies of people with ME/CFS respond to position changes and whether problems with their blood vessel function might be involved. Researchers compared 67 women with ME/CFS to 48 healthy women, measuring their blood pressure, heart rate, body temperature patterns, and blood markers related to blood vessel health. They found that people with ME/CFS had higher blood pressure and heart rate, disrupted daily temperature rhythms, and elevated levels of substances in the blood that suggest blood vessel problems.

Autonomic Nervous System

E2 ModerateCohortPEM not required

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): impact of self-reported fatigue and illness duration.

Byrne, Hollie, Josev, Elisha K, Knight, Sarah J et al.·Brain structure & function·2023

This study looked at the size of the hypothalamus (a small part of the brain that controls many body functions) in teenagers with ME/CFS compared to healthy teenagers. While the overall brain structure sizes were similar between the two groups, researchers found that in ME/CFS patients, certain areas of the hypothalamus were slightly larger when fatigue was more severe, and other areas grew larger with longer illness duration. This suggests the hypothalamus may play a role in ME/CFS, though more research is needed to understand what this means.

E2 ModerateCohortPEM unclearObservational

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome.

Friedberg, Fred, Adamowicz, Jenna L, Bruckenthal, Patricia et al.·Scientific reports·2023

This study looked at how men and women with ME/CFS respond differently to a simple exercise test (a six-minute walk). Researchers tracked fatigue levels and heart function for 15 days in 37 ME/CFS patients and 14 healthy people. Women with ME/CFS felt more tired after the first walk test, while men reported fewer work limitations in the days after exercise. Surprisingly, the study did not find the expected differences between men and women in how long it took to recover.

E2 ModerateDiagnosticPEM requiredCross-Sectional

Evaluating case diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): toward an empirical case definition.

Conroy, Karl E, Islam, Mohammed F, Jason, Leonard A·Disability and rehabilitation·2023

This study looked at how doctors diagnose ME/CFS by analyzing symptoms reported by over 2,300 patients from around the world. Researchers used statistical methods to identify which symptoms tend to occur together, then compared their findings to three existing diagnostic guidelines. They found that the symptoms cluster into seven main groups, with post-exertional malaise (worsening after activity), cognitive problems, and sleep issues being particularly important.

SleepPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID.

Yamamoto, Yukichika, Otsuka, Yuki, Tokumasu, Kazuki et al.·Journal of clinical medicine·2023

This study looked at 234 people with long COVID to understand why some developed ME/CFS (a severe fatigue condition) while others didn't. Researchers found that people who developed ME/CFS had significantly higher levels of ferritin, a protein that stores iron, in their blood compared to those with long COVID fatigue alone or no fatigue. The finding was especially strong in women, suggesting that a simple blood test measuring ferritin might help predict who is at risk of developing ME/CFS after COVID-19.

Biomarkers

Do diagnostic criteria for ME matter to patient experience with services and interventions? Key results from an online RDS survey targeting fatigue patients in Norway.

Kielland, Anne, Liu, Jing, Jason, Leonard A·Journal of health psychology·2023

This study surveyed 660 people with ME/CFS in Norway to understand how different diagnostic criteria and symptoms affect their experiences with treatments and healthcare services. Most patients reported that available interventions had little benefit or made them feel worse. The researchers found that post-exertional malaise (a hallmark symptom where activity makes fatigue and other symptoms worse) was strongly linked to how patients tolerated different treatments, suggesting this symptom should be a key consideration when recommending interventions.

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 requiredCross-Sectional

Health system support among patients with ME/CFS in Switzerland.

Tschopp, Rea, König, Rahel S, Rejmer, Protazy et al.·Journal of Taibah University Medical Sciences·2023

This Swiss study surveyed 169 ME/CFS patients to understand their experiences with the healthcare system. Patients faced long delays in getting diagnosed (averaging 6.7 years), saw many doctors before getting correct answers (11.1 appointments on average), and were frequently told their symptoms were psychological rather than physical. The study found that doctors in Switzerland lack knowledge about ME/CFS, leading to frustration, inappropriate treatments, and some patients traveling abroad for proper diagnosis.

Diagnostics

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa.

Hannestad, Ulf, Apostolou, Eirini, Sjögren, Per et al.·Frontiers in medicine·2023

This study found that people with ME/CFS who caught COVID-19 showed signs of a dormant virus (adenovirus) waking up in their mouth and throat. The researchers compared saliva samples from ME/CFS patients and healthy people, and only the ME/CFS patients showed this reactivation after COVID-19 infection. This suggests that ME/CFS patients may have a weakened immune system that cannot keep these latent viruses under control when faced with a new infection like COVID-19.

Immune System

E2 ModerateCohortPEM not requiredObservational

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression.

Kendler, Kenneth S, Rosmalen, Judith G M, Ohlsson, Henrik et al.·Psychological medicine·2023

This study looked at the family histories of over 5 million Swedish people to understand whether ME/CFS, fibromyalgia, and irritable bowel syndrome share common genetic roots. Researchers found that people with these conditions have a distinctive pattern of genetic risk that affects multiple body systems—including pain, mood, immune function, and sleep—rather than being limited to one specific area like depression or rheumatoid arthritis. This suggests these functional somatic disorders may arise from a complex genetic vulnerability affecting several interconnected systems rather than a single cause.

Severe MEPost-Exertional Malaise

Characterizing Sjögren-Associated Fatigue: A Distinct Phenotype from ME/CFS.

Kim, Laura, Kedor, Claudia, Buttgereit, Frank et al.·Journal of clinical medicine·2023

This study compared fatigue in people with Sjögren's syndrome (an autoimmune disease affecting moisture-producing glands) to fatigue in ME/CFS patients. While both groups experience severe tiredness, the researchers found important differences: Sjögren's patients recovered their muscle strength within an hour of activity, whereas ME/CFS patients typically experience worsening symptoms hours after exertion. Only a small portion of Sjögren's patients met ME/CFS diagnostic criteria, suggesting these are distinct conditions despite some symptom overlap.

E2 ModerateBehavioralPEM not requiredLongitudinal

Uplifts and hassles are related to worsening in chronic fatigue syndrome: a prospective study.

Friedberg, Fred, Adamowicz, Jenna L, Bruckenthal, Patricia et al.·Journal of translational medicine·2023

This study tracked 128 ME/CFS patients over six months to see how daily pleasant and unpleasant events related to whether their illness got better, stayed the same, or got worse. Patients who worsened experienced more intense unpleasant events and had fewer pleasant events over time, while those who improved showed the opposite pattern. The findings suggest that the balance between daily hassles and uplifts may play a role in how ME/CFS progresses.