Evidence browser

SleepPost-Exertional Malaise

Pediatric Post-Acute Sequelae of SARS-CoV-2 Infection.

Jason, Leonard A, Johnson, Madeline, Torres, Chelsea·Fatigue : biomedicine, health & behavior·2023

This study compared young people recovering from long COVID (PASC) with young people who have ME/CFS to understand how their symptoms differ. Researchers asked 19 parents about their child's symptoms during initial COVID infection and again later, then compared these to 19 young people with ME/CFS. Most PASC symptoms improved over time, but fatigue and sleep problems stayed high—similar to what ME/CFS patients experience.

E2 ModerateCohortPEM unclearLongitudinal

Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome.

Parker, Megan, Sawant, Hannah Brady, Flannery, Thuvia et al.·Journal of medical virology·2023

This study tested whether a structured pacing protocol—a method that carefully matches activity levels to what your body can handle—could help people with long COVID reduce post-exertional symptom exacerbation (PESE), the worsening of symptoms that happens after physical, mental, or emotional effort. Over 6 weeks, 31 participants worked with a clinician via phone calls to follow a personalized pacing plan. The results showed that PESE episodes dropped significantly, from an average of 3.4 per week to 1.1 per week, and participants reported improvements in their overall quality of life.

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS).

Haffke, Milan, Freitag, Helma, Rudolf, Gordon et al.·Journal of translational medicine·2022

This study looked at whether blood vessel function is damaged in people with long COVID and ME/CFS. Researchers tested blood vessel function and measured specific proteins in the blood that reflect endothelial (blood vessel lining) health. They found that some patients with both conditions showed signs of blood vessel dysfunction, and had abnormal levels of certain proteins compared to healthy people.

E2 ModerateMechanismPEM requiredObservational

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome.

Germain, Arnaud, Giloteaux, Ludovic, Moore, Geoffrey E et al.·JCI insight·2022

Researchers studied 60 ME/CFS patients and 45 healthy people by measuring thousands of chemical substances in their blood before and after intense exercise tests done 24 hours apart. They found that ME/CFS patients had very different chemical patterns in their blood, especially after exercise and during the 24-hour recovery period, suggesting their bodies struggle to respond to and recover from physical exertion in ways that may explain post-exertional malaise (the worsening of symptoms after activity).

Energy MetabolismPost-Exertional Malaise

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study.

Retornaz, Frédérique, Rebaudet, Stanislas, Stavris, Chloé et al.·Journal of translational medicine·2022

This study found that long-COVID patients and ME/CFS patients have very similar symptoms and muscle problems. Researchers measured electrical activity in leg muscles during and after exercise in both groups and found comparable patterns of muscle fatigue. This suggests that COVID-19 infection may trigger ME/CFS-like illness in some people.

Activity measurement in pediatric chronic fatigue syndrome.

Loiacono, Bernardo, Sunnquist, Madison, Nicholson, Laura et al.·Chronic illness·2022

This study compared how active children with ME/CFS are compared to healthy children. Researchers used activity tracking devices and asked children to report their own activity levels. Children with ME/CFS were less active overall and had unusual sleep-wake patterns, with more activity at night and delayed activity during the day. The good news is that children with ME/CFS could accurately report their own activity levels.

Immune SystemPost-Exertional Malaise

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity.

Kedor, Claudia, Freitag, Helma, Meyer-Arndt, Lil et al.·Nature communications·2022

This study followed 42 people with long-lasting fatigue after COVID-19 infection for six months and compared them to people with similar chronic fatigue from other causes. Most participants experienced moderate to severe fatigue that interfered with daily life. The researchers found that many of these post-COVID patients had reduced hand grip strength and blood markers suggesting possible inflammation and poor blood flow, which may help explain why their bodies struggle to recover.

Immune SystemPost-Exertional Malaise

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?

Ryabkova, Varvara A, Gavrilova, Natalia Y, Fedotkina, Tamara V et al.·Diagnostics (Basel, Switzerland)·2022

This Russian study looked at 56 people with ME/CFS and 14 people with post-COVID syndrome to understand how their bodies function differently. The researchers found that both groups had similar patterns of immune system problems, heart rate changes when standing up, and reduced blood flow in small vessels. Importantly, fatigue severity was linked to many other ME/CFS symptoms but not to anxiety or depression.

A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants.

Leem, Jong-Han, Jeon, Hyoung-Eun, Nam, Hun et al.·Environmental analysis, health and toxicology·2022

This study tested whether a special two-day exercise test could detect post-exertional malaise (PEM)—the worsening of symptoms after physical activity—in people with ME/CFS who had been exposed to humidifier disinfectants. The researchers had 29 participants complete an exercise test, rest for 24 hours, then repeat it. They found that performance noticeably declined on the second day, showing that PEM is real and measurable.

E2 ModerateCohortPEM unclearObservational

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.

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study.

Cook, Dane B, VanRiper, Stephanie, Dougherty, Ryan J et al.·PloS one·2022

Researchers tested 214 people with ME/CFS and 189 healthy controls using exercise bikes to see how their bodies responded to physical activity. They found that people with ME/CFS had unusual patterns during exercise: they breathed inefficiently, their hearts didn't speed up as much as expected, but they felt the exercise was harder than controls thought it was. These differences remained even when comparing people with similar fitness levels.

Factors Influencing the Prognosis of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ghali, Alaa, Lacout, Carole, Fortrat, Jacques-Olivier et al.·Diagnostics (Basel, Switzerland)·2022

This study looked at 168 ME/CFS patients to understand what factors help people recover or significantly improve. The research found that only about 13% of patients experienced recovery or substantial improvement over time. Interestingly, patients who were older when they first got sick were more likely to improve, and people who received a diagnosis sooner (without long delays) also had better outcomes. The study confirms that ME/CFS is generally a serious condition with poor prognosis, but suggests that improvement is possible at any age.

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Australian primary care patients: only part of the story?

Orji, Nneka, Campbell, Julie A, Wills, Karen et al.·BMC public health·2022

This study looked at how many people in Australia have ME/CFS by examining medical records from primary care clinics between 2015-2019. Researchers found that roughly 95-104 people per 100,000 have ME/CFS in Australia, but they also discovered that many patients avoid visiting their doctors because of stigma, disbelief in the condition, and lack of available treatments. The researchers concluded that the real number of people with ME/CFS is likely much higher than what their numbers show.

Long COVID OverlapPost-Exertional Malaise

ME/CFS and Post-Exertional Malaise among Patients with Long COVID.

Jason, Leonard A, Dorri, Joseph A·Neurology international·2022

Researchers studied 465 people with long-term COVID symptoms to see how many also had ME/CFS (a serious condition causing extreme fatigue and worsening after activity). They found that about 6 in 10 people with long COVID met the medical criteria for ME/CFS. Interestingly, some people thought they had ME/CFS when they didn't, while others had ME/CFS without realizing it—showing that self-diagnosis alone isn't reliable.

Chronic Fatigue and Postexertional Malaise in People Living With Long COVID: An Observational Study.

Twomey, Rosie, DeMars, Jessica, Franklin, Kelli et al.·Physical therapy·2022

This study looked at 213 people with long COVID to measure how severe their fatigue and postexertional malaise (PEM—worsening of symptoms after activity) were. Researchers found that over 71% had chronic fatigue as severe as or worse than other serious illnesses, and nearly 59% experienced PEM similar to what people with ME/CFS report. The study highlights that fatigue and symptom flare-ups after activity are major problems that need careful monitoring and should shape how doctors design rehabilitation programs.

E2 ModerateCohortPEM not requiredObservational

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.

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study.

Wright, Jack, Astill, Sarah L, Sivan, Manoj·International journal of environmental research and public health·2022

This study asked 477 people with Long COVID about their physical activity levels before and after illness, and how exercise affected their symptoms. Participants were much less active after getting Long COVID and needed more help with daily tasks. Most people (about 75%) reported that physical activity made their symptoms worse, while only about 1% said it improved them.

E2 ModerateCohortPEM requiredLongitudinal

Improvement of Long COVID symptoms over one year.

Oliveira, Carlos R, Jason, Leonard A, Unutmaz, Derya et al.·Frontiers in medicine·2022

This study compared people with Long COVID (PASC) to people with ME/CFS, conditions that cause similar symptoms like fatigue and brain fog. Over one year, people with Long COVID showed improvement in five key symptoms including fatigue and post-exertional malaise, while people with ME/CFS did not improve. The researchers used a symptom questionnaire to track changes and found that Long COVID and ME/CFS look similar at first, but Long COVID appears to follow a different course.

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.