Long COVID vs ME/CFS: symptoms, biomarkers, trials and research
A data-driven comparison of Long COVID and Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) built from the Open Source Medicine Foundation biomarker atlases, PubMed literature feeds, ClinicalTrials.gov registry extract and post-acute infection syndrome (PAIS) cohort database.
Roughly half of people with Long COVID lasting more than six months meet ME/CFS criteria, and the two conditions share post-exertional malaise as a defining feature. Much of the ME/CFS research community has reoriented toward Long COVID cohorts because the trigger and onset date are known, so findings flow in both directions.
What each condition is
Long COVID
Also known as: PASC, Post-Acute Sequelae of COVID-19, Post-COVID-19 condition
Long COVID describes symptoms that persist or emerge more than three months after SARS-CoV-2 infection and cannot be explained by another diagnosis. The World Health Organization calls it post-COVID-19 condition; the US National Institutes of Health uses the term PASC. Common features include fatigue, post-exertional symptom exacerbation, cognitive difficulties, orthostatic intolerance, breathlessness and chest pain. Because the triggering infection is known and recent, Long COVID has attracted large prospective cohorts (RECOVER, PHOSP-COVID) and the largest clinical-trial pipeline of any post-infectious illness.
Atlas scope: Molecular, metabolic, and immunological alterations reported in post-acute sequelae of COVID-19 (PASC / long COVID) compared to healthy controls and fully recovered individuals.
OSMF resources: biomarker atlas · literature feed
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
Also known as: CFS, ME, Systemic Exertion Intolerance Disease
ME/CFS is a chronic, multi-system illness defined clinically by a substantial reduction in activity, post-exertional malaise (PEM), unrefreshing sleep and either cognitive impairment or orthostatic intolerance. It frequently begins after an infection, including mononucleosis (EBV), SARS, Q fever, Ross River virus and now SARS-CoV-2, but many cases have no identified trigger. There is no validated diagnostic test; research biomarkers centre on energy metabolism, immune signalling and autonomic function.
Atlas scope: Molecular, metabolic, immunological, and autonomic alterations in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) compared to healthy sedentary and active controls — including post-exertional malaise (PEM) phenotypes.
OSMF resources: biomarker atlas · literature feed
Side-by-side summary
| Measure | Long COVID | ME/CFS |
|---|---|---|
| Biomarkers catalogued | 77 | 46 |
| Biomarker categories covered | metabolic (23), inflammatory (14), vascular (8), immune (7), coagulation (6), proteomic (5), lipidomic (4), neurological (4), microbiome (4), viral (2) | inflammatory (10), metabolic (10), autonomic (6), immune (5), mitochondrial (4), functional (4), autoimmune (3), neurological (2), urinary (2) |
| Markers with LOINC codes | 25 | 13 |
| Literature studies tracked | 75 | 75 |
| Most recent tracked study | 07 Jul 2026 | 06 Jul 2026 |
| Registered trials (all statuses) | 341 | 146 |
| Recruiting / not yet recruiting | 81 | 26 |
| Active, not recruiting | 26 | 9 |
| Completed | 150 | 75 |
| Terminated / withdrawn / suspended | 27 | 15 |
| Unknown status | 57 | 21 |
| Named cohorts in PAIS database | 8 | 3 |
| Therapeutic agents tracked | 405 | 179 |
Trial condition matching: Long COVID uses the registry’s mapped condition label; ME/CFS uses the registry’s mapped condition label. Trials listing both conditions: 13.
Shared biomarkers (18)
Markers catalogued in both atlases, matched by normalised name or LOINC code. Rows marked direction differs are reported to change in opposite or inconsistent directions across the two literatures, which may reflect different comparison groups, assays or disease stages rather than true biology.
| Biomarker | Category | Direction in Long COVID | Direction in ME/CFS | Matched by | Sources |
|---|---|---|---|---|---|
| Interleukin-6 (IL-6) direction differs | inflammatory | Increased vs HC, R | Mixed / conflicting vs HC | LOINC 26881-5 | Lai et al. 2023; Corbitt et al. 2019 |
| Tumor Necrosis Factor-α (TNF-α) direction differs | inflammatory | Increased vs HC, R | Mixed / conflicting vs HC | LOINC 3074-8 | Lai et al. 2023; Saito et al. 2024; Corbitt et al. 2019 |
| Interleukin-1α (IL-1α) Interleukin-1 (IL-1α/β) in ME/CFS | inflammatory | Increased vs HC, R | Increased vs HC | LOINC 26864-3 | Saito et al. 2024; Corbitt et al. 2019 |
| C-Reactive Protein (CRP) direction differs | inflammatory | Increased vs HC, R | Mixed / conflicting vs HC | LOINC 1988-5 | Lai et al. 2023; Strawbridge et al. 2019 |
| Soluble CD14 (sCD14) sCD14 in ME/CFS | inflammatory | Increased vs HC, R | Increased vs HC | LOINC 30180-5 | Saito et al. 2024; Saito et al. 2024 |
| Transforming Growth Factor-β (TGF-β) | inflammatory | Increased vs HC, R | Increased vs HC | LOINC 27999-4 | Lai et al. 2023; Corbitt et al. 2019 |
| Interleukin-8 (IL-8) Interleukin-8 (IL-8 / CXCL8) in ME/CFS direction differs | inflammatory | Increased vs HC | Mixed / conflicting vs HC | LOINC 26998-9 | Thomas et al. 2024; Corbitt et al. 2019 |
| Interleukin-10 (IL-10) | inflammatory | Mixed / conflicting vs HC, R | Mixed / conflicting vs HC | LOINC 26862-5 | Thomas et al. 2024; Corbitt et al. 2019 |
| ATP (plasma) | metabolic | Decreased vs HC, R | Decreased vs HC | name | Saito et al. 2024; Saito et al. 2024 |
| Serine | metabolic | Decreased vs HC, R | Decreased vs HC — LC overlap | name | Saito et al. 2024; Saito et al. 2024 |
| Sarcosine | metabolic | Decreased vs HC, R | Decreased vs HC — LC overlap | name | Saito et al. 2024; Saito et al. 2024 |
| Kynurenine | metabolic | Increased vs HC | Increased vs HC | name | Saito et al. 2024; Saito et al. 2024 |
| Lactate Lactate (blood) in ME/CFS | metabolic | Increased vs HC | Increased vs HC | LOINC 2524-7 | Baalbaki et al. 2025; Holden et al. 2020 |
| Ceramides Ceramides (plasma) in ME/CFS | lipidomic / metabolic | Decreased vs R (fully recovered) | Decreased vs HC | name | Pérez-Mazliah et al. 2024; Saito et al. 2024 |
| Resistin direction differs | vascular / inflammatory | Increased vs HC | Mixed / conflicting vs HC | LOINC 42702-4 | Lai et al. 2023; Strawbridge et al. 2019 |
| Neurofilament light chain (NfL) direction differs | neurological | Increased vs HC | Mixed / conflicting vs HC | LOINC 94635-5 | Lai et al. 2023; Maksoud et al. 2023 |
| Anti-GPCR autoantibodies Anti-GPCR autoantibodies (panel) in ME/CFS | immune / autoimmune | Increased vs HC | Increased vs HC — LC/PACVS overlap | name | Wilhelm et al. 2026; Maksoud et al. 2023 |
| Cortisol Cortisol (diurnal rhythm) in ME/CFS | proteomic / neurological | Mixed / conflicting vs HC | Mixed / conflicting vs HC | LOINC 2143-6 | Baalbaki et al. 2025; Maksoud et al. 2023 |
Distinct biomarkers
Top 15 markers catalogued for one condition but not matched in the other. Full lists are on the Long COVID atlas and the ME/CFS atlas.
Only in Long COVID atlas (59)
- Flt-1 / sVEGFR-1 Increased inflammatory
- CCL4 (MIP-1β) Increased inflammatory
- Cystatin D (CST5) Increased inflammatory
- Pro-inflammatory cytokines (composite) Decreased inflammatory
- Ferritin Mixed / conflicting inflammatory
- Serum Amyloid A (SAA) Increased inflammatory
- Aspartate Decreased metabolic
- Asparagine Decreased metabolic
- Glutamine Decreased metabolic
- Arginine Decreased metabolic
- Histidine Decreased metabolic
- TCA cycle intermediates Increased metabolic
- 5-Hydroxykynurenine Increased metabolic
- Serotonin Increased metabolic
- Putrescine Increased metabolic
+44 more in the atlas.
Only in ME/CFS atlas (28)
- Leptin Increased inflammatory
- Acylcarnitines (composite) Increased metabolic
- C16 Acylcarnitine (palmitoylcarnitine) Increased metabolic
- C18 Acylcarnitine (stearoylcarnitine) Increased metabolic
- Free carnitine Mixed / conflicting metabolic
- ATP production capacity Decreased mitochondrial
- Mitochondrial membrane potential Decreased mitochondrial
- Pyruvate dehydrogenase activity Decreased mitochondrial
- Oxidative phosphorylation efficiency Decreased mitochondrial
- NK cell cytotoxicity Decreased immune
- CD8+ T cell perforin Decreased immune
- RNase L (37-kDa fragment) Increased immune
- Neutrophil elastase Increased immune
- CD26 / sCD26 (DPPIV) Mixed / conflicting immune
- β2-adrenergic receptor autoantibodies Increased autoimmune
+13 more in the atlas.
Overlapping therapeutics under investigation (28)
Agents that appear in registered trials or the OSMF therapeutic-agent database for both Long COVID and ME/CFS. Inclusion means an agent is being studied, not that it works.
- Acupuncture
- Coenzyme Q10 (CoQ10)
- Conventional Exercise
- Cycling
- Exercise
- Fluvoxamine
- Hyperbaric Oxygen Therapy (HBOT)
- Immunoadsorption
- Inebilizumab
- Inspiratory Muscle Training
- Intravenous Immunoglobulin (IVIG)
- Low-Dose Naltrexone (LDN)
- Lumbrokinase
- Metformin
- Mindful And Conscious Movement-Based Exercise
- N-Acetylcysteine (NAC)
- Photobiomodulation Therapy
- Probiotics
- Processing Speed Training
- Pyridostigmine
- Reaction Time Training
- Swimming
- Telerehabilitation
- Trans-Auricular Vagus Nerve Stimulation: High Intensity
- Trans-Auricular Vagus Nerve Stimulation: Low Intensity
- Transcutaneous Non-Invasive Vagus Nerve Stimulation
- Transcutaneous Vagus Nerve Stimulation
- Transcutaneous Vagus Nerve Stimulator
Trials enrolling both conditions (13)
- NCT07724834 · CD19-B Cell Depletion in PAIS-ME/CFS Patients (Not Yet Recruiting, Phase 2)
- NCT07454395 · Is Swimming a More Tolerable Form of Movement for Individuals With Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome? (Suspended)
- NCT06978582 · Effectiveness and Safety of a Tele-Rehabilitation Program on Fatigue and Related Variables in Chronic Fatigue Syndrome and Post COVID Syndrome (Active Not Recruiting)
- NCT06968104 · Vagus Nerve Stimulation to the Ear to Improve Symptoms in Post-COVID-19 and ME/CFS (Active Not Recruiting)
- NCT06585254 · tVNS in Long COVID-19 (Active Not Recruiting)
- NCT06511050 · Lumbrokinase for Adults With Long Covid, Post-treatment Lyme Disease Syndrome, and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Recruiting, Phase 1)
- NCT06366724 · LIFT: Life Improvement Trial (Recruiting, Phase 2)
- NCT05741112 · The Long COVID-19 Wearable Device Study (Recruiting)
- NCT06128967 · A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial (Completed, Phase 3)
- NCT05608629 · Vagus Nerve Stimulation as Treatment for Long Covid (Completed)
Showing 10 of 13; see the trials tracker.
Research cohorts
Long COVID cohorts (8)
- NIH RECOVER-Adult Cohort prospective non inception, n=15,000, biobank active
- Long COVID Host Genetics Initiative GWAS registry linkage, n=6,450, biobank active
- Patient-Led Long COVID international cohort (Davis 2021) survey, n=3,762, biobank not_applicable
- PHOSP-COVID (UK post-hospitalisation COVID-19) prospective non inception, n=2,320, biobank active
- Jinyintan (Wuhan) COVID-19 discharge cohort (Huang) prospective non inception, n=1,733, biobank unknown
- Bergen COVID-19 home-isolated cohort (Blomberg) prospective inception, n=312, biobank active
- PACVS registry cohort (Semmler/Mundorf) cross sectional, n=191, biobank unknown
- Amsterdam Long COVID muscle-biopsy PEM cohort (Appelman) case control, n=46, biobank unknown
ME/CFS cohorts (3)
- DecodeME ME/CFS GWAS registry linkage, n=15,579, biobank active
- UK ME/CFS Biobank (CureME, LSHTM) cross sectional, n=632, biobank active
- NIH Intramural ME/CFS Deep-Phenotyping Study (Walitt/Nath 2024) cross sectional, n=57, biobank active
Recent research
Latest Long COVID studies
Latest ME/CFS studies
Frequently asked questions
Can you have both Long COVID and ME/CFS?
They are not mutually exclusive. Both are diagnosed clinically, and a person can meet criteria for Long COVID and ME/CFS at the same time. In the OSMF data the two conditions share 18 catalogued biomarkers, 13 registered trials list both conditions, and 0 cohorts in the PAIS database are relevant to both. Overlap in a dataset is not evidence that one condition causes the other.
How do the biomarker profiles differ?
Long COVID has 77 catalogued markers, led by metabolic (23), inflammatory (14), vascular (8). ME/CFS has 46, led by inflammatory (10), metabolic (10), autonomic (6). 18 markers appear in both atlases, and 6 of those are reported to move in different directions (Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), C-Reactive Protein (CRP)...). Categories unique to Long COVID: coagulation, lipidomic, microbiome, proteomic, vascular, viral; unique to ME/CFS: autoimmune, autonomic, functional, mitochondrial, urinary.
Which has more active clinical trials?
Long COVID has more: 107 active or recruiting trials versus 35 for ME/CFS (registry snapshot 07 Oct 2026). Totals including completed, terminated and unknown-status studies are 341 for Long COVID and 146 for ME/CFS. Trial counts measure research attention, not treatment efficacy.
Which condition has more recent research?
OSMF tracks 75 recent PubMed-indexed studies for Long COVID (latest 07 Jul 2026) and 75 for ME/CFS (latest 06 Jul 2026). The feeds hold a rolling window of recent publications, so they indicate current publication pace rather than lifetime output. See the Long COVID feed and the ME/CFS feed for the full lists.
Are the same treatments being studied for both?
28 agents appear in the trial registry or therapeutic-agent database for both conditions, including Acupuncture, Coenzyme Q10 (CoQ10), Conventional Exercise, Cycling, Exercise. All of these are investigational for these indications; none is an approved treatment for either condition. Overlap usually reflects shared hypotheses (immune modulation, autonomic support, antiviral or anti-inflammatory strategies) rather than demonstrated efficacy.
Which has larger research cohorts?
The PAIS cohort database lists 8 named cohorts for Long COVID and 3 named cohorts for ME/CFS, the largest being NIH RECOVER-Adult Cohort (15,000 enrolled) and DecodeME ME/CFS GWAS (15,579 enrolled). Cohorts with stored biospecimens and open external access are the most useful for cross-condition biomarker validation.
Related comparisons
Cite this page
@misc{osmf_longcovid_vs_mecfs,
author = {Open Source Medicine Foundation},
title = {Long COVID vs ME/CFS: symptoms, biomarkers, trials and research compared},
year = {2026},
howpublished = {\url{https://research.opensourcemed.info/compare/long-covid-vs-me-cfs.html}},
note = {Data as of 2026-10-07}
}Get OSMF research updates
New biomarker, trial and cohort data, summarised for patients and researchers.
Last updated 07 Oct 2026 (page build). Underlying data: literature feeds 07 Jul 2026 / 06 Jul 2026; trial registry 07 Oct 2026; atlases 29 Jun 2026 / 29 Jun 2026. Generated by scripts/build_compare_pages.py.