ME/CFS vs Lyme disease: symptoms, biomarkers, trials and research
A data-driven comparison of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Lyme Disease built from the Open Source Medicine Foundation biomarker atlases, PubMed literature feeds, ClinicalTrials.gov registry extract and post-acute infection syndrome (PAIS) cohort database.
Persistent fatigue after treated Lyme disease is one of the historical arguments for an infectious origin of ME/CFS, and some PTLDS patients meet ME/CFS case definitions. Diagnostic serology exists for Lyme but not for ME/CFS, which shapes the biomarker tables below.
What each condition is
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
Lyme Disease
Also known as: Lyme borreliosis, Borrelia burgdorferi infection, Post-treatment Lyme disease syndrome (PTLDS), Chronic Lyme
Lyme disease is a tick-borne bacterial infection caused by Borrelia burgdorferi and related species. Early disease is diagnosed by the erythema migrans rash and two-tier serology, and treated with antibiotics. A minority of treated patients develop post-treatment Lyme disease syndrome (PTLDS): fatigue, musculoskeletal pain and cognitive symptoms lasting six months or longer. The OSMF literature feed for this condition focuses on the chronic and post-treatment phase, while the biomarker atlas spans acute serology through neuroborreliosis and persistent-symptom phenotypes.
Atlas scope: Serologic, cerebrospinal fluid, molecular, and inflammatory biomarkers in Borrelia burgdorferi infection — from early localized disease through disseminated, neuroborreliosis, and post-treatment persistent symptom phenotypes.
OSMF resources: biomarker atlas · literature feed
Side-by-side summary
| Measure | ME/CFS | Lyme disease |
|---|---|---|
| Biomarkers catalogued | 46 | 36 |
| Biomarker categories covered | inflammatory (10), metabolic (10), autonomic (6), immune (5), mitochondrial (4), functional (4), autoimmune (3), neurological (2), urinary (2) | serologic (9), csf (6), inflammatory (6), molecular (4), coinfection (4), chronic (4), functional (3) |
| Markers with LOINC codes | 13 | 6 |
| Literature studies tracked | 75 | 75 |
| Most recent tracked study | 06 Jul 2026 | 05 Jul 2026 |
| Registered trials (all statuses) | 146 | 2 |
| Recruiting / not yet recruiting | 26 | 2 |
| Active, not recruiting | 9 | 0 |
| Completed | 75 | 0 |
| Terminated / withdrawn / suspended | 15 | 0 |
| Unknown status | 21 | 0 |
| Named cohorts in PAIS database | 3 | 1 |
| Therapeutic agents tracked | 179 | 8 |
Trial condition matching: ME/CFS uses the registry’s mapped condition label; Lyme disease uses keyword matching on registry condition and title fields. Trials listing both conditions: 1.
Shared biomarkers (4)
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 ME/CFS | Direction in Lyme disease | Matched by | Sources |
|---|---|---|---|---|---|
| Interleukin-6 (IL-6) direction differs | inflammatory | Mixed / conflicting vs HC | Increased vs HC | LOINC 26881-5 | Corbitt et al. 2019; Lantos et al. 2021 |
| Interleukin-10 (IL-10) direction differs | inflammatory | Mixed / conflicting vs HC | Increased vs HC | LOINC 26862-5 | Corbitt et al. 2019; Lantos et al. 2021 |
| C-Reactive Protein (CRP) | inflammatory | Mixed / conflicting vs HC | Mixed / conflicting vs HC | LOINC 1988-5 | Strawbridge et al. 2019; Lantos et al. 2021 |
| Heart rate variability (RMSSD) Heart rate variability (PTLDS) in Lyme disease | autonomic / chronic | Decreased vs HC | Decreased vs HC | name | Nelson et al. 2019; Aucott et al. 2014 |
Distinct biomarkers
Top 15 markers catalogued for one condition but not matched in the other. Full lists are on the ME/CFS atlas and the Lyme disease atlas.
Only in ME/CFS atlas (42)
- Interleukin-1 (IL-1α/β) Increased inflammatory
- Transforming Growth Factor-β (TGF-β) Increased inflammatory
- Tumor Necrosis Factor-α (TNF-α) Mixed / conflicting inflammatory
- Interleukin-8 (IL-8 / CXCL8) Mixed / conflicting inflammatory
- Leptin Increased inflammatory
- Resistin Mixed / conflicting inflammatory
- Acylcarnitines (composite) Increased metabolic
- C16 Acylcarnitine (palmitoylcarnitine) Increased metabolic
- C18 Acylcarnitine (stearoylcarnitine) Increased metabolic
- Free carnitine Mixed / conflicting metabolic
- Lactate (blood) Increased metabolic
- ATP production capacity Decreased mitochondrial
- Mitochondrial membrane potential Decreased mitochondrial
- Pyruvate dehydrogenase activity Decreased mitochondrial
- Oxidative phosphorylation efficiency Decreased mitochondrial
+27 more in the atlas.
Only in Lyme disease atlas (32)
- B. burgdorferi EIA (screening) Increased serologic
- IgG immunoblot (≥5 of 10 bands) Increased serologic
- IgM immunoblot (≥2 of 3 bands) Increased serologic
- C6 peptide ELISA (VisE) Increased serologic
- Anti-VlsE antibodies Increased serologic
- Anti-OspC antibodies Increased serologic
- Anti-OspA antibodies Increased serologic
- Anti-p41 (flagellin) antibodies Increased serologic
- CSF CXCL13 Increased csf
- CSF anti-Bb antibody index Increased csf
- CSF lymphocytic pleocytosis Increased csf
- CSF protein elevation Increased csf
- CSF oligoclonal bands Mixed / conflicting csf
- CSF glucose Mixed / conflicting csf
- Interferon-γ (IFN-γ) Increased inflammatory
+17 more in the atlas.
Overlapping therapeutics under investigation (3)
Agents that appear in registered trials or the OSMF therapeutic-agent database for both ME/CFS and Lyme disease. Inclusion means an agent is being studied, not that it works.
- Intravenous Immunoglobulin (IVIG)
- Lumbrokinase
- N-Acetylcysteine (NAC)
Trials enrolling both conditions (1)
- NCT06511050 · Lumbrokinase for Adults With Long Covid, Post-treatment Lyme Disease Syndrome, and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Recruiting, Phase 1)
Research cohorts
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
Lyme disease cohorts (1)
- Johns Hopkins SLICE early-Lyme cohort (Aucott/Rebman) prospective inception, n=234, biobank active
Recent research
Latest ME/CFS studies
Latest Lyme disease studies
Frequently asked questions
Can you have both ME/CFS and Lyme disease?
They are not mutually exclusive. Both are diagnosed clinically, and a person can meet criteria for ME/CFS and Lyme disease at the same time. In the OSMF data the two conditions share 4 catalogued biomarkers, 1 registered trial 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?
ME/CFS has 46 catalogued markers, led by inflammatory (10), metabolic (10), autonomic (6). Lyme disease has 36, led by serologic (9), csf (6), inflammatory (6). 4 markers appear in both atlases, and 2 of those are reported to move in different directions (Interleukin-6 (IL-6), Interleukin-10 (IL-10)). Categories unique to ME/CFS: autoimmune, autonomic, immune, metabolic, mitochondrial, neurological, urinary; unique to Lyme disease: chronic, coinfection, csf, molecular, serologic.
Which has more active clinical trials?
ME/CFS has more: 35 active or recruiting trials versus 2 for Lyme disease (registry snapshot 07 Oct 2026). Totals including completed, terminated and unknown-status studies are 146 for ME/CFS and 2 for Lyme disease. Condition matching for Lyme disease relies on keyword matching of registry condition fields and may miss trials. Trial counts measure research attention, not treatment efficacy.
Which condition has more recent research?
OSMF tracks 75 recent PubMed-indexed studies for ME/CFS (latest 06 Jul 2026) and 75 for Lyme disease (latest 05 Jul 2026). The feeds hold a rolling window of recent publications, so they indicate current publication pace rather than lifetime output. See the ME/CFS feed and the Lyme disease feed for the full lists.
Are the same treatments being studied for both?
3 agents appear in the trial registry or therapeutic-agent database for both conditions, including Intravenous Immunoglobulin (IVIG), Lumbrokinase, N-Acetylcysteine (NAC). 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 3 named cohorts for ME/CFS and 1 named cohort for Lyme disease, the largest being DecodeME ME/CFS GWAS (15,579 enrolled) and Johns Hopkins SLICE early-Lyme cohort (Aucott/Rebman) (234 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_mecfs_vs_lyme,
author = {Open Source Medicine Foundation},
title = {ME/CFS vs Lyme disease: symptoms, biomarkers, trials and research compared},
year = {2026},
howpublished = {\url{https://research.opensourcemed.info/compare/me-cfs-vs-lyme.html}},
note = {Data as of 2026-10-07}
}Get OSMF research updates
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Last updated 07 Oct 2026 (page build). Underlying data: literature feeds 06 Jul 2026 / 08 Jul 2026; trial registry 07 Oct 2026; atlases 29 Jun 2026 / 29 Jun 2026. Generated by scripts/build_compare_pages.py.