Long COVID vs Lyme disease: symptoms, biomarkers, trials and research
A data-driven comparison of Long COVID 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.
Post-treatment Lyme disease syndrome was, before 2020, the best-studied example of persistent symptoms after a treated infection. Comparing it with Long COVID tests whether a bacterial and a viral trigger converge on similar inflammatory and autonomic signatures.
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
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 | Long COVID | Lyme disease |
|---|---|---|
| Biomarkers catalogued | 77 | 36 |
| Biomarker categories covered | metabolic (23), inflammatory (14), vascular (8), immune (7), coagulation (6), proteomic (5), lipidomic (4), neurological (4), microbiome (4), viral (2) | serologic (9), csf (6), inflammatory (6), molecular (4), coinfection (4), chronic (4), functional (3) |
| Markers with LOINC codes | 25 | 6 |
| Literature studies tracked | 75 | 75 |
| Most recent tracked study | 07 Jul 2026 | 05 Jul 2026 |
| Registered trials (all statuses) | 341 | 2 |
| Recruiting / not yet recruiting | 81 | 2 |
| Active, not recruiting | 26 | 0 |
| Completed | 150 | 0 |
| Terminated / withdrawn / suspended | 27 | 0 |
| Unknown status | 57 | 0 |
| Named cohorts in PAIS database | 8 | 1 |
| Therapeutic agents tracked | 405 | 8 |
Trial condition matching: Long COVID 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 (3)
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 Lyme disease | Matched by | Sources |
|---|---|---|---|---|---|
| Interleukin-6 (IL-6) | inflammatory | Increased vs HC, R | Increased vs HC | LOINC 26881-5 | Lai et al. 2023; Lantos et al. 2021 |
| C-Reactive Protein (CRP) direction differs | inflammatory | Increased vs HC, R | Mixed / conflicting vs HC | LOINC 1988-5 | Lai et al. 2023; Lantos et al. 2021 |
| Interleukin-10 (IL-10) direction differs | inflammatory | Mixed / conflicting vs HC, R | Increased vs HC | LOINC 26862-5 | Thomas et al. 2024; Lantos et al. 2021 |
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 Lyme disease atlas.
Only in Long COVID atlas (74)
- Tumor Necrosis Factor-α (TNF-α) Increased inflammatory
- Interleukin-1α (IL-1α) Increased inflammatory
- Soluble CD14 (sCD14) Increased inflammatory
- Flt-1 / sVEGFR-1 Increased inflammatory
- CCL4 (MIP-1β) Increased inflammatory
- Cystatin D (CST5) Increased inflammatory
- Pro-inflammatory cytokines (composite) Decreased inflammatory
- Transforming Growth Factor-β (TGF-β) Increased inflammatory
- Interleukin-8 (IL-8) Increased inflammatory
- Ferritin Mixed / conflicting inflammatory
- Serum Amyloid A (SAA) Increased inflammatory
- ATP (plasma) Decreased metabolic
- Serine Decreased metabolic
- Sarcosine Decreased metabolic
- Aspartate Decreased metabolic
+59 more in the atlas.
Only in Lyme disease atlas (33)
- 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
+18 more in the atlas.
Overlapping therapeutics under investigation (4)
Agents that appear in registered trials or the OSMF therapeutic-agent database for both Long COVID and Lyme disease. Inclusion means an agent is being studied, not that it works.
- Intravenous Immunoglobulin (IVIG)
- Ivermectin
- 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
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
Lyme disease cohorts (1)
- Johns Hopkins SLICE early-Lyme cohort (Aucott/Rebman) prospective inception, n=234, biobank active
Recent research
Latest Long COVID studies
Latest Lyme disease studies
Frequently asked questions
Can you have both Long COVID and Lyme disease?
They are not mutually exclusive. Both are diagnosed clinically, and a person can meet criteria for Long COVID and Lyme disease at the same time. In the OSMF data the two conditions share 3 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?
Long COVID has 77 catalogued markers, led by metabolic (23), inflammatory (14), vascular (8). Lyme disease has 36, led by serologic (9), csf (6), inflammatory (6). 3 markers appear in both atlases, and 2 of those are reported to move in different directions (C-Reactive Protein (CRP), Interleukin-10 (IL-10)). Categories unique to Long COVID: coagulation, immune, lipidomic, metabolic, microbiome, neurological, proteomic, vascular, viral; unique to Lyme disease: chronic, coinfection, csf, functional, molecular, serologic.
Which has more active clinical trials?
Long COVID has more: 107 active or recruiting trials versus 2 for Lyme disease (registry snapshot 07 Oct 2026). Totals including completed, terminated and unknown-status studies are 341 for Long COVID 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 Long COVID (latest 07 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 Long COVID feed and the Lyme disease feed for the full lists.
Are the same treatments being studied for both?
4 agents appear in the trial registry or therapeutic-agent database for both conditions, including Intravenous Immunoglobulin (IVIG), Ivermectin, 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 8 named cohorts for Long COVID and 1 named cohort for Lyme disease, the largest being NIH RECOVER-Adult Cohort (15,000 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_longcovid_vs_lyme,
author = {Open Source Medicine Foundation},
title = {Long COVID vs Lyme disease: symptoms, biomarkers, trials and research compared},
year = {2026},
howpublished = {\url{https://research.opensourcemed.info/compare/long-covid-vs-lyme.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 / 08 Jul 2026; trial registry 07 Oct 2026; atlases 29 Jun 2026 / 29 Jun 2026. Generated by scripts/build_compare_pages.py.