Long COVID Vascular Health Panel Interpretation Guide

Pathway Analysis

These sections summarize biologically relevant immune signaling pathways that may be suggested by patterns observed across the measured analytes. These pathway groupings are derived from known functional relationships between cytokines, chemokines, and growth factors.

Activation of a given pathway is inferred when multiple related markers are elevated in a coordinated manner. These interpretations are intended to provide biological context for the results and should be considered alongside clinical findings and other laboratory data.

Pro-Angiogenic and Vascular Growth Signaling

Back to top

This pathway reflects activation of pro-angiogenic signaling processes that promote new blood vessel formation, endothelial proliferation, and tissue remodeling. These signals are commonly elevated in contexts of tissue repair, hypoxia, inflammation, and tumor-associated angiogenesis.

Core Growth and Angiogenic Factors

  • Angiopoietin-2 – Regulates vascular remodeling and destabilization of existing vessels, facilitating angiogenic sprouting in the presence of VEGF signaling1.
  • FGF-1 (Fibroblast Growth Factor-1) – Promotes endothelial cell proliferation and differentiation, contributing to angiogenesis and tissue repair2.
  • HB-EGF – A member of the EGF family involved in wound healing, epithelial repair, and vascular growth3.
  • HGF (Hepatocyte Growth Factor) – Stimulates endothelial motility, proliferation, and morphogenesis; plays a key role in angiogenesis and tissue regeneration4.
  • Leptin – Beyond its metabolic role, leptin has pro-angiogenic properties and can promote endothelial cell activation and vascular growth5.
  • PLGF (Placental Growth Factor) – A VEGF family member that amplifies angiogenic signaling, particularly under inflammatory or ischemic conditions6.

Supporting Context

  1. Akwii RG, Sajib MS, Zahra FT, Mikelis CM. Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology. Cells. May 17 2019;8(5)doi:10.3390/cells8050471
  2. Xie Y, Su N, Yang J, et al. FGF/FGFR signaling in health and disease. Signal Transduct Target Ther. 09 2020;5(1):181. doi:10.1038/s41392-020-00222-7
  3. Singh B, Carpenter G, Coffey RJ. EGF receptor ligands: recent advances. F1000Res. 2016;5doi:10.12688/f1000research.9025.1
  4. Nakamura T, Sakai K, Matsumoto K. Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. Jan 2011;26 Suppl 1:188-202. doi:10.1111/j.1440-1746.2010.06549.x
  5. Bruno A, Ferrante G, Di Vincenzo S, Pace E, La Grutta S. Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection? Front Physiol. 2021;12:776963. doi:10.3389/fphys.2021.776963
  6. Dewerchin M, Carmeliet P. PlGF: a multitasking cytokine with disease-restricted activity. Cold Spring Harb Perspect Med. Aug 01 2012;2(8)doi:10.1101/cshperspect.a011056

Angiogenic Regulation and Vascular Stabilization

Back to top

This pathway reflects regulatory mechanisms that balance angiogenic activity, maintain vascular integrity, and modulate endothelial responses.

Core Regulatory Factors

  • BMP9 (Bone Morphogenetic Protein 9) – Promotes vascular quiescence and stability through endothelial signaling pathways1.
  • Endoglin (CD105) – A co-receptor involved in TGF-β signaling that regulates endothelial proliferation and vascular remodeling2.
  • Follistatin – Modulates growth factor signaling (including activins), contributing to regulation of tissue remodeling and vascular homeostasis3.

Supporting Context

  1. Dunmore BJ, Upton PD, Auckland K, et al. Reduced circulating BMP9 and pBMP10 in hospitalized COVID-19 patients. Pulm Circ. Jan 2023;13(1):e12192. doi:10.1002/pul2.12192
  2. Schoonderwoerd MJA, Goumans MTH, Hawinkels LJAC. Endoglin: Beyond the Endothelium. Biomolecules. Feb 12 2020;10(2)doi:10.3390/biom10020289
  3. Morianos I, Papadopoulou G, Semitekolou M, Xanthou G. Activin-A in the regulation of immunity in health and disease. J Autoimmun. Nov 2019;104:102314. doi:10.1016/j.jaut.2019.102314

Lymphatic Vessel Growth and Remodeling

Back to top

This pathway represents signaling involved in lymphangiogenesis—the formation and remodeling of lymphatic vessels—which plays a key role in fluid balance, immune cell trafficking, and tissue repair.

Core Lymphangiogenic Factors

  • VEGF-C – Primary driver of lymphatic endothelial cell growth and lymphatic vessel formation1.
  • VEGF-D – Supports lymphangiogenesis and contributes to vascular remodeling in certain pathological contexts1.

Supporting Context

  1. Deng H, Zhang J, Wu F, et al. Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect. Cancers (Basel). Feb 11

Endothelial Activation and Vascular Inflammation

Back to top

This pathway reflects activation of the vascular endothelium, often in response to inflammatory stimuli, infection, or vascular injury. Endothelial activation promotes leukocyte adhesion, vascular permeability, and inflammatory signaling.

Core Endothelial Activation Markers

  • Endothelin-1 – A potent vasoconstrictor that also contributes to endothelial dysfunction and vascular inflammation1.
  • sICAM-1 (Soluble Intercellular Adhesion Molecule-1) – Reflects endothelial activation and facilitates leukocyte adhesion and transmigration2.
  • sVCAM-1 (Soluble Vascular Cell Adhesion Molecule-1) – Mediates adhesion of immune cells to the endothelium and is associated with inflammatory vascular responses3.

Supporting Context

  1. Davenport AP, Hyndman KA, Dhaun N, et al. Endothelin. Pharmacol Rev. Apr 2016;68(2):357-418. doi:10.1124/pr.115.011833
  2. Lawson C, Wolf S. ICAM-1 signaling in endothelial cells. Pharmacol Rep. 2009;61(1):22-32. doi:10.1016/s1734-1140(09)70004-0
  3. Troncoso MF, Ortiz-Quintero J, Garrido-Moreno V, et al. VCAM-1 as a predictor biomarker in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis. Sep 01 2021;1867(9):166170. doi:10.1016/j.bbadis.2021.166170

Coagulation and Thrombotic Pathway Activity

Back to top

This pathway reflects processes involved in coagulation, fibrinolysis, and platelet activation. Elevations may indicate increased thrombotic activity, endothelial injury, or dysregulation of clotting pathways.

Core Coagulation and Platelet Markers

  • ADAMTS13 – Regulates von Willebrand factor activity and plays a key role in maintaining normal coagulation balance1.
  • D-Dimer – A fibrin degradation product that reflects active clot formation and breakdown2.
  • sP-Selectin – Marker of platelet activation and endothelial interaction, contributing to thrombus formation3.

Supporting Context

  1. DeYoung V, Singh K, Kretz CA. Mechanisms of ADAMTS13 regulation. J Thromb Haemost. Dec 2022;20(12):2722-2732. doi:10.1111/jth.15873
  2. Lippi G, Mullier F, Favaloro EJ. D-dimer: old dogmas, new (COVID-19) tricks. Clin Chem Lab Med. Apr 25 2023;61(5):841-850. doi:10.1515/cclm-2022-0633
  3. André P. P-selectin in haemostasis. Br J Haematol. Aug 2004;126(3):298-306. doi:10.1111/j.1365-2141.2004.05032.x

Acute Phase Inflammatory Signaling

Back to top

This pathway reflects systemic inflammatory responses mediated by acute phase reactants produced primarily by the liver.

Core Acute Phase Marker

  • SAA (Serum Amyloid A) – A highly sensitive acute phase protein that rises rapidly in response to inflammation, infection, or tissue injury1,2.

Supporting Context

  1. Ye RD, Sun L. Emerging functions of serum amyloid A in inflammation. J Leukoc Biol. Dec 2015;98(6):923-9. doi:10.1189/jlb.3VMR0315-080R
  2. Almusalami EM, Lockett A, Ferro A, Posner J. Serum amyloid A-A potential therapeutic target for hyper-inflammatory syndrome associated with COVID-19. Front Med (Lausanne). 2023;10:1135695. doi:10.3389/fmed.2023.1135695