Evidence browser

BiomarkersAutonomic Nervous SystemImmune SystemCognitive Impairment

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Azcue, N, Prada, A, Del Pino, R et al.·Scientific reports·2026

Researchers compared immune markers called autoantibodies in people with post-COVID condition, ME/CFS, and healthy controls. They found that people with ME/CFS had higher levels of antibodies against certain nerve receptors (β2 adrenergic), and these antibodies were associated with autonomic nervous system problems and memory changes. However, this is a single cross-sectional study, and autoimmunity remains one of several proposed mechanisms—it is not yet clear whether these antibodies are a cause or a consequence of ME/CFS.

BiomarkersCognitive ImpairmentLong COVID OverlapPost-Exertional Malaise

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Aregawi, Lillian, Walitt, Brian, Sullivan, Patti et al.·Brain communications·2026

Researchers measured levels of norepinephrine (a brain chemical) in cerebrospinal fluid from people with ME/CFS, Long COVID, and Parkinson's disease, comparing them to healthy volunteers. They observed that norepinephrine pathway activity was lower in all three patient groups, and in Long COVID patients with post-exertional malaise, this reduction was particularly pronounced. This is one study in a small sample, and it remains unclear whether these findings fully explain fatigue and brain fog or apply directly to ME/CFS.

BiomarkersLong COVID Overlap

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Jones, Ansley E, Mira-Sanchez, Margarita, Khan, Zain et al.·Journal of intensive care medicine·2026

This study examined blood clotting patterns in 93 people who survived severe COVID-19 requiring hospitalization, testing them 15 months after discharge. Researchers observed that those with lingering post-COVID symptoms—particularly fatigue and post-exertional malaise (worsening after activity)—showed altered clotting characteristics on specialized blood tests, specifically higher fibrinogen levels. However, this is a single cross-sectional study and does not establish whether these clotting changes cause the symptoms or are simply associated with them.

NeuroinflammationBiomarkersImmune SystemLong COVID Overlap

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Omdal, Roald, Lenning, Ole Bernt, Jonsson, Grete et al.·Brain, behavior, & immunity - health·2026

A study of 48 people with long-COVID and 48 recovered controls found that fatigue was much more severe in the long-COVID group, but common blood markers of inflammation and cellular stress did not differ between the groups. This suggests that the fatigue in long-COVID may not be driven by the types of inflammation typically measured in blood tests, though the researchers note their findings are preliminary and limited to the biomarkers they tested.

Severe MEDiagnosticsLong COVID OverlapPost-Exertional Malaise

Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.

Tomaskovic, Aleksandar, Weber, Vincent, Ochmann, David T et al.·Sports medicine - open·2026

A cross-sectional study of 92 severely ill post-COVID patients found that those meeting ME/CFS criteria had lower measured aerobic capacity (oxygen uptake and power output) on exercise testing compared to post-COVID patients without ME/CFS. Two-thirds of all patients showed objective signs of work disability on testing, and these measurements correlated with patients' own reports of disability and their employment status. The relevance of these findings specifically to ME/CFS requires caution, as the study enrolled primarily post-COVID patients, and the overlap between these conditions remains incompletely understood.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al.·Open forum infectious diseases·2026

Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.

Unmasking the Long-Term Effects of COVID-19 With a Focus on Chronic Fatigue Syndrome: A Community-Based Study From India.

Gupta, Arti, Rajan, Vishnu, Aravindakshan, Rajeev et al.·Cureus·2025

This study looked at 500 COVID-19 survivors in rural India to see how many developed chronic fatigue syndrome (CFS)—a condition causing severe, lasting tiredness and other symptoms. About 21% of the COVID-19 survivors developed CFS, with older people, women, and those with existing health conditions at higher risk. The study found that fatigue, joint pain, and muscle pain were common problems after COVID-19.

Immune SystemLong COVID Overlap

Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·Biomedicines·2025

This study compared immune system markers in people with ME/CFS and Long COVID to those of healthy individuals. Both patient groups showed similar immune problems: lower levels of protective immune cells and higher levels of inflammatory substances in their blood. The findings suggest that ME/CFS and Long COVID may involve very similar underlying immune dysfunction.

E2 ModerateCohortPEM unclearObservational

Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection.

Hadidchi, Roham, Patel, Bhakti, Madan, Japji et al.·Journal of translational medicine·2025

This study found that people who had COVID-19 are more likely to develop ME/CFS in the years following infection compared to people who never had COVID-19. Women, and people with existing autoimmune or anxiety disorders, appear to be at higher risk. Importantly, having COVID-19 again did not increase the risk further, and blood tests during acute COVID were not able to predict who would later develop ME/CFS.

Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis.

Sirotiak, Zoe, Adamowicz, Jenna L, Thomas, Emily B K·Journal of clinical psychology in medical settings·2025

This study looked at brain fog and concentration problems in people with ME/CFS and long COVID using data from over 27,000 Americans. Researchers found that people with ME/CFS are about 6 times more likely to experience cognitive difficulties like memory and concentration problems compared to people without these conditions, while long COVID increases the risk about 2 times. People who have both ME/CFS and long COVID together face even greater cognitive challenges.

E2 ModerateCohortPEM requiredLongitudinal

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Unger, Elizabeth R, Lin, Jin-Mann S, Wisk, Lauren E et al.·JAMA network open·2024

This study followed over 4,300 people for up to 12 months to see whether COVID-19 infection caused ME/CFS-like symptoms. Researchers found that about 3-4% of people reported ME/CFS-like symptoms after their acute illness, but this rate was similar whether they had tested positive or negative for COVID-19. The results suggest that while some people do develop long-lasting symptoms after illness, COVID-19 may not be uniquely causing ME/CFS more often than other infections.

DiagnosticsLong COVID Overlap

E2 ModerateCohortPEM unclearObservational

Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study.

Zerón-Rugerio, María Fernanda, Zaragozá, Maria Cleofé, Domingo, Joan Carles et al.·Chronobiology international·2024

This study looked at sleep patterns and daily body rhythms in ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had lower activity levels, worse sleep quality, and unhealthy cholesterol levels compared to healthy controls. The study also found that problems with blood vessel function may connect sleep disruptions to heart health problems in ME/CFS patients.

E2 ModeratePEM unclearRegistry-Resource

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

Reuken, P A, Besteher, B, Finke, K et al.·European archives of psychiatry and clinical neuroscience·2024

This study followed over 1,000 people who had long-lasting symptoms after COVID-19 infection. Researchers found that about 31% of patients met the diagnostic criteria for ME/CFS at their first visit, but this dropped to 19% at a second visit months later. While patients reported feeling less fatigued and having fewer concentration problems over time, many continued to experience long-lasting symptoms that significantly affected their daily lives.

Cognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM not requiredObservational

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-Term Impairment of Working Ability in Subjects under 60 Years of Age Hospitalised for COVID-19 at 2 Years of Follow-Up: A Cross-Sectional Study.

Frallonardo, Luisa, Ritacco, Annunziata Ilenia, Amendolara, Angela et al.·Viruses·2024

This study followed 322 people under age 60 who were hospitalized with COVID-19 and checked on them about 2 years later. Researchers found that 42% of these patients reported difficulty working compared to before they got sick, even though they had recovered from the acute infection. The study identified that women, people with diabetes, and those who needed oxygen during hospitalization were more likely to have lasting work problems.

E2 ModerateCohortPEM not requiredLongitudinal

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.

E2 ModerateCohortPEM unclearObservational

Post-Acute Sequelae of COVID-19 (PASC) in Pediatrics: Factors That Impact Symptom Severity and Referral to Treatment.

Soprano, Catherine M, Ngo, Ryan, Konys, Casey A et al.·Children (Basel, Switzerland)·2023

This study looked at how long COVID (called PASC) affects children and teenagers, comparing their experiences to adults. The researchers reviewed medical records to understand what symptoms young people had and whether they were referred to specialized treatment programs. The main finding was that young people with long COVID tend to have less severe symptoms than adults, though many young patients were not referred for treatment even when they needed it.

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.

E2 ModerateCohortPEM unclearLongitudinal

Fatigue presentation, severity, and related outcomes in a prospective cohort following post-COVID-19 hospitalization in British Columbia, Canada.

Magel, Tianna, Meagher, Emily, Boulter, Travis et al.·Frontiers in medicine·2023

This study followed 88 people who were hospitalized with COVID-19 to see how many experienced long-lasting fatigue afterward. Two-thirds of patients had fatigue at 3 months, though this improved somewhat by 6 months, with about 60% still experiencing it. People who had more existing health conditions before COVID-19 were more likely to develop fatigue, suggesting that previous health status may influence recovery.