• Study reports abnormally high VTE and high bleed risk in critically ill COVID-19 patients and calls for more effective prevention strategies.
  • Clinicians at NHS hospitals are supporting the care of COVID-19 patients with the use of geko™ devices to reduce the risk of blood clots in the most at risk patients.
Learn more Contact us

COVID-19 Potentially an Endothelial Disease

12th May 2020

Just one cell layer thin, the endothelium lines all organs, including the miles of arteries, veins and capillaries that course through the body.

Endothelial cells release wide range substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function and platelet adhesion1.

Functions of a healthy endothelium include:

  • Prevention of inappropriate blood clotting
  • Relaxation of arteries, promoting normal blood pressure
  • Prevention of inflammation and plaques
  • Smooth blood flow to deliver nutrients for cell metabolism
  • Facilitation of glucose uptake and healthy blood sugars
Enlarge

In SARS-CoV-2 endothelial dysfunction is observed as a common clinical manifestation in seriously ill Covid-19 patients with pre-exiting conditions, such as: hypertension, diabetes, obesity, and cardiovascular disease2.

The C-19 virus accesses host cells by binding its spike to the ACE2 receptor, a gateway to the lungs and widely expressed on endothelial cells in multiple organs, shifting the vascular equilibrium towards constriction of blood vessels, subsequent organ ischaemia (interruption of blood supply), inflammation associated tissue oedema (swelling) and a pro-coagulant state (blood clotting)3.

Early data suggests C-19 endotheliitis (inflammation of the endothelium) can explain the systemic impaired macro and microcirculatory function. This hypothesis provides a rationale for therapies that stabilise and protect the endothelium, such as use of anti-inflammatory, anti-cytokine drugs, ACE inhibitors, and statins, used along-side blood thinners for clot prevention4.

Impaired blood flow mechanics are also identified as a mechanism that can trigger endothelial dysfunction (endotheliitis)5.

Normal blood flow is known to exert shear stress on the vascular endothelium thereby releasing the protective substances such as nitric oxide and prostacyclin6.

Endothelial dysfunction occurs predominantly at sites of low shear stress, where the blood might be reduced or turbulent, which leads to damage of endothelial cells which in turn can initiate inflammation and blood clotting.  Whereas, regions of the vasculature exposed to shear stresses, where the blood flow is laminar (steady), these regions are protected7. Clinically proven to produce physiologically normal shear stress on endothelial cells are mechanical compression devices, such as intermittent pneumatic compression (IPC) or the recently introduced geko™ device. These devices provide an adjunct to drug therapy and when drug strategies may be impractical or contraindicated. They increase production of anti-thrombotic, pro-fibrinolytic, vasodilation agents8.

The innovative geko™ device is clinically proven to improve systemic endothelial function9. Recommended by NICE and cleared by the FDA for blood clot prevention, the geko™ is a small battery powered, disposable, neuromuscular electro-stimulation device that is applied non-invasively to the skin over the common peroneal nerve at the side of the knee. It gently stimulates the nerve, once every second, activating the calf and foot muscle pumps resulting in increased steady blood flow in the deep veins of the calf, at rate equal to 60%10 of walking, exerting systemic protective shear stress on the endothelium in immobile, critically-ill Covid-19 patients and without a patient having to move. All other mechanical IPC devices increase blood flow only once every minute.

Highly portable, the geko™ device is:

  • Disposable – no need to sterilise after single patient use.
  • No decontamination required – not the case with other mechanical devices.
  • Easy-to-fit – minimal training.
  • Less nurse-to-patient contact time – reduced C-19 viral load risk.
  • No tripping hazard – no leads or hoses.

References:

  1. Rajendran. P et al. The Vascular Endothelium and Human Diseases. Int J Biol Sci. 2013; 9(10): 1057–1069.
  2. Guzik. T M et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovac Res. 2020 Apr 30: cvaa106.
  3. Varga. S et al. Zsuzsanna VEndothelial cell infection and endotheliitis in COVID-19. The Lancet. Volume 395, Issue 10234. P1417-1418, MAY 02, 2020.
  4. Varga. S et al. Zsuzsanna VEndothelial cell infection and endotheliitis in COVID-19. The Lancet. Volume 395, Issue 10234. P1417-1418, MAY 02, 2020.
  5. Jeng-Jiann Chiu et al. Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives. Physiol Rev. 2011 Jan: 91 (1): 10.1152/physrev.00047.2009.
  6. Aamer Sandoo et al. The Endothelium and Its Role in Regulating Vascular Tone. Open Cardiovasc Med J. 2010; 4: 302–312. Published online 2010 Dec 23. doi: 2174/1874192401004010302.
  7. DAVIES P F et al. Shear Stress Biology of the Endothelium. Annals of Biomedical Engineering, Vol. 33, No. 12, December 2005 (© 2005) pp. 1714–1718 DOI: 10.1007/s10439-005-8774-0.
  8. Chen A H et al Intermittent Pneumatic Compression Devices – Physiological Mechanisms of Action. Eur J Vasc Endovasc Surg 21, 383–392 (2001) doi:10.1053/ejvs.2001.1348, available online.
  9. Lavi S et al. Peripheral muscle stimulation increases coronary blood flow. Springer 23rd November 2015.
  10. Tucker A, et al. Augmentation of venous, arterial and microvascular blood supply in the leg by isometric neuromuscular stimulation via the peroneal nerve. The International journal of angiology: official publication of the International College of Angiology, Inc. 2010 Spring;19(1): e31-7.

 

Sue Davenport – VP Marketing Communications
12th May 2020

See more Covid-19 information