Readily Measurable Products of SARS-Cov-2 Endothelial Cell Injury

This is the second in a series of discussions about the relationship between hemostasis and inflammation. These discussions were part of our Rutgers CLSC 5124 Advanced Hemostasis course that features answers provided by our participants.

List the readily measurable products of SARS-Cov-2 mediated endothelial cell injury.

SARS-CoV-2 is increasingly being recognized as a disease of endothelial cell damage, not only a respiratory disease.¹ The virus binds to the ACE-2 receptor present on endothelial cells (as well as alveolar cells), causing endothelial damage that triggers inflammation in the body and disrupting hemostasis.^1,2

VWF
One marker of endothelial damage is increased von Willebrand factor (VWF). After endothelial cell injury, platelets bind to the damaged epithelium, initiating a pro-coagulant process.³ The increase in activated platelets results in increased VWF in plasma.³ Another theory to explain increased VWF in SARS-CoV-2 is the damage caused by the virus entering the cells causes the release of VWF from the Weibel-Palade bodies.⁴

D-Dimer
SARS-CoV-2 infection patients with elevated D-dimer are more likely to progress to severe SARS-CoV-2, require intensive care, and have higher mortality rates.¹ This can lead to what the American Society of Hematology (ASH) has termed “COVID-19 -associated coagulopathy.”⁵ Because of increased endothelial injury that in response activates the coagulation cascade, there is an increase in clotting products which are then broken down and able to be measured via the D-dimer test.⁵

LDH
Lactate dehydrogenase (LDH) is another biomarker that may be of prognostic value in SARS-CoV-2. It is theorized this is due to endothelial cell damage, but also due to decreased efficiency in oxygen delivery and blood flow as LDH is increased in cases of tissue damage and hypoxia.⁶ LDH is released from damaged and dying cells, which explains why it is increased in cases of severe endothelial cell damage.⁶

CRP
As damaged endothelial cells trigger inflammatory processes, C-reactive protein (CRP), a general marker of inflammation, increases due to the overproduction of inflammatory cytokines from tissue destruction.⁷ However, because CRP is an acute phase reactant, it is not specific for the inflammatory processes of SARS-CoV-2.⁶

1. Six I, Guillaume N, Jacob V, et al. The endothelium and COVID-19: an increasingly clear link brief title: endotheliopathy in COVID-19. Int J Mol Sci. 2022;23:6196. doi:10.3390/ijms23116196
2. Xu SW, Ilyas I, Weng JP. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacol SIn. 2022. doi:10.1038/s41401-022-00998-0
3. Levy JH, Iba T, Gardiner EE. Endothelial injury in COVID-19 and acute infections. Arterioscler Thromb Vasc Biol. 2021;41:1774–6. doi:10.1161/atvbaha.121.316101
4. Ladikou EE, Sivaloganathan H, Milne KM, et al. Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19? Clin Med. 2020;20:e178–82. doi:10.7861/clinmed.2020-0346
5. Lehmann A, Prosch H, Zehetmayer S, et al. Impact of persistent D-dimer elevation following recovery from COVID-19. PLOS ONE. 2021;16:e0258351. doi:10.1371/journal.pone.0258351
6. Fialek B, Pruc M, Smereka J, et al. Diagnostic value of lactate dehydrogenase in COVID-19: a systematic review and meta-analysis. Cardiol J. 2022. doi:10.5603/cj.a2022.0056
7. Ali N. Elevated level of C‐reactive protein may be an early marker to predict risk for severity of COVID‐19. J Med Virol. 2020;92(11):2409-2411. doi:10.1002/jmv.26097