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Peer-Reviewed Literature Synthesis

Long COVID Biomarker Atlas

Molecular, metabolic, and immunological alterations reported in post-acute sequelae of COVID-19 (PASC / long COVID) compared to healthy controls and fully recovered individuals.

Literature Overview

Synthesized from systematic reviews and primary omics studies published through 2025. No single biomarker defines long COVID; a multi-system profile is emerging.

Immune & Inflammatory Dysfunction

Persistent low-grade inflammation early post-infection, with evidence of immune exhaustion or suppression at later timepoints. Elevated IL-6, TNF-Ξ±, CRP, and sCD14 are among the most replicated findings.

Metabolic & Mitochondrial Impairment

Reduced amino acid metabolism, depleted ceramides, elevated TCA cycle intermediates, and reduced ATP β€” consistent with mitochondrial dysfunction and impaired energy production in fatigue-dominant phenotypes.

Endothelial, Coagulation & Vascular

Elevated D-dimer, fibrinogen, von Willebrand factor, and markers of platelet hyperactivation. Microclot formation and impaired fibrinolysis have been documented in post-acute COVID cohorts.

Searchable Alterations Database

Filter by category or direction. Comparison groups: HC = healthy controls (SARS-CoV-2 unexposed); R = recovered without persistent symptoms.

Temporal dynamics matter

Biomarker patterns evolve over months. Early long COVID may show low-grade inflammation (elevated IL-6, CRP), while at 6+ months some cohorts show reduced pro-inflammatory cytokines compared to recovered individuals β€” suggesting immune exhaustion rather than normalization (Kallaste et al., 2025). Recovered individuals without symptoms may still show metabolomic alterations vs. never-infected controls at 12 months post-infection (Saito et al., 2024).

Related atlases: All Atlases Β· PACVS Β· ME/CFS Β· Lyme Β· Gulf War Illness

Marker / Metabolite Direction Category vs. Comparison Associated Symptoms Key Reference

Category Deep Dives

Pathway-level summaries from primary studies and systematic reviews.

πŸ”₯ Cytokines & Inflammatory Mediators

  • IL-6 ↑ LC
  • TNF-Ξ± ↑ LC
  • IL-1Ξ± ↑ LC
  • CRP ↑ LC
  • sCD14 (monocyte activation) ↑ LC
  • Flt-1 / sVEGFR-1 ↑ LC
  • CCL4 (MIP-1Ξ²) ↑ at 3 mo
  • CST5 (Cystatin D) ↑ at 6 mo
  • Pro-inflammatory cytokines (late) ↓ vs R
  • TGF-Ξ² ↑ pulmonary LC

⚑ Metabolites & Energy Pathways

  • ATP (plasma) ↓ LC
  • Serine ↓ LC
  • Sarcosine ↓ LC
  • Aspartate / Asparagine ↓ LC
  • Glutamine / Arginine / Histidine ↓ LC
  • TCA cycle intermediates (succinate, etc.) ↑ LC
  • Kynurenine pathway metabolites ↑ LC
  • Serotonin / Putrescine ↑ LC
  • 5-Aminolevulinate / Porphobilinogen ↑ LC
  • Uracil / Thymine ↓ LC

🩸 Coagulation & Vascular Markers

  • D-dimer ↑ LC
  • Fibrinogen ↑ LC
  • von Willebrand factor (vWF) ↑ LC
  • PAI-1 (plasminogen activator inhibitor) ↑ LC
  • Platelet activation markers (P-selectin) ↑ LC
  • Amyloid-fibrin microclots ↑ LC
  • Resistin ↑ LC
  • ICAM-1 / VCAM-1 ↑ LC
  • Endothelial dysfunction markers ↑ LC

🧠 Neurological & Autoimmune Markers

  • Neurofilament light chain (NfL) ↑ neuro LC
  • GFAP (glial fibrillary acidic protein) ↑ neuro LC
  • Autoantibodies (anti-IFN-Ξ±, anti-IFN-Ο‰) ↑ LC
  • Anti-GPCR autoantibodies ↑ LC
  • Anti-nuclear antibodies Variable
  • Complement activation (C3a, C5a) ↑ LC
  • Ξ²2-microglobulin ↑ LC

🧬 Lipidomics & Proteomics

  • Ceramides (plasma) ↓ LC
  • Sphingolipid species Altered
  • 447 lipid species profile Discriminant
  • Complement & coagulation cascade proteins ↑ LC
  • Acute phase proteins (SAA, AGP) ↑ LC
  • Extracellular matrix remodeling proteins Altered
  • Cortisol / DHEA ratio Altered

🦠 Viral Persistence & Microbiome

  • SARS-CoV-2 spike protein (circulating) Detected in subset
  • Persistent S1 spike antigen (plasma, ≀12 mo) ↑ Walt/Brigham 2023
  • SARS-CoV-2 RNA (blood/tissue) Detected in subset
  • SARS-CoV-2-specific CD8 T cells (activation) ↕ under investigation
  • IFN-Ξ³ (SARS-CoV-2-specific T cell) ↕ stable/persistent
  • Gut microbiome diversity ↓ LC
  • Faecalibacterium prausnitzii ↓ LC
  • Opportunistic pathogen abundance ↑ LC
  • Microbial-derived metabolites (SCFAs) Altered
  • EBV / HHV-6 reactivation markers Reported

Key References

Primary sources underpinning this atlas. Full reference lists available in each linked publication.

Primary Study β€” Viral Persistence

Persistent circulating SARS-CoV-2 spike antigen in post-acute sequelae of COVID-19

Swank Z et al. Clin Infect Dis. 2023;76(3):e487–e490 (Walt lab, Brigham and Women's). n=63; antigen detected ≀12 months post-diagnosis
DOI: 10.1093/cid/ciac722 β†’
Primary Study β€” T Cell Immunology

Robust antibody and T cell responses tracked longitudinally in Long COVID patients

Krishna B et al. J Gen Virol. 2025 (University of Cambridge). Stable IFN-Ξ³ and increasing IL-2 SARS-CoV-2-specific responses
DOI: 10.1099/jgv.0.002102 β†’
Systematic Review

Blood Biomarkers of Long COVID: A Systematic Review

Thomas C et al. Mol Diagn Ther. 2024;28(5):537–574
DOI: 10.1007/s40291-024-00731-z β†’
Systematic Review

Biomarkers in Long COVID-19: A Systematic Review

Lai YJ et al. Front Med. 2023;10:1085988 β€” 113 biomarkers across 28 studies
DOI: 10.3389/fmed.2023.1085988 β†’
Systematic Review

The Omics Landscape of Long COVID

Baalbaki N et al. Allergy. 2025;80(4):932–948 β€” 29 omics studies
DOI: 10.1111/all.16526 β†’
Primary Study β€” Metabolomics

Metabolomic and Immune Alterations in Long COVID Patients with ME/CFS

Saito S et al. Front Immunol. 2024;15:1341843 β€” 2,584 metabolites, 12-month follow-up
DOI: 10.3389/fimmu.2024.1341843 β†’
Primary Study β€” Metabolomics

Mitochondrial Dysfunction in Long COVID: Multiplatform Metabolomics

PΓ©rez-Mazliah M et al. J Proteome Res. 2024 β€” 46 discriminating metabolites, n=40 LC vs 40 recovered
DOI: 10.1021/acs.jproteome.3c00706 β†’
Primary Study β€” Cytokines

Long COVID and Biomarker Dysregulation: A Shift Toward Immune Exhaustion?

Kallaste A et al. Medicina. 2025;61(6):996 β€” Longitudinal Olink inflammation panel
DOI: 10.3390/medicina61060996 β†’
Systematic Review

Autoantibodies in Long COVID: A Systematic Review

Wilhelm F et al. Lancet Infect Dis. 2026;26(4):e220–e230
DOI: 10.1016/S1473-3099(25)00411-6 β†’
Primary Study β€” Coagulation

Prevalence of Symptoms, Comorbidities, Fibrin Amyloid Microclots and Platelet Pathology in Long COVID

Pretorius E et al. Cardiovasc Diabetol. 2023;22:148
DOI: 10.1186/s12933-023-01931-4 β†’
Disclaimer: This page is an educational synthesis of published peer-reviewed research and does not constitute medical advice. Biomarker findings vary substantially across studies due to differences in long COVID definitions, comparison groups, time since infection, acute disease severity, and symptom phenotypes. Direction of change (↑/↓) reflects the predominant finding in the cited literature but may not be universal. No single biomarker has been validated as a standalone diagnostic test for long COVID. Consult qualified healthcare providers for clinical interpretation.