Could Soluble Endothelial Protein C Receptor Levels Recognize SARS-CoV2-Positive Patients Requiring Hospitalization?
Adult
Aged
Biomarkers
/ blood
COVID-19
/ blood
Endothelial Protein C Receptor
/ blood
Female
Fibrin Fibrinogen Degradation Products
/ biosynthesis
Hospitalization
Humans
Inflammation
/ blood
Male
Middle Aged
Outpatients
Phenotype
Predictive Value of Tests
Prognosis
RNA, Viral
/ metabolism
ROC Curve
Regression Analysis
Risk Factors
SARS-CoV-2
Thrombosis
/ blood
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
pubmed:
24
3
2021
medline:
16
11
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients' requirement for hospitalization. Plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value. In our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers. In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.
Identifiants
pubmed: 33756504
doi: 10.1097/SHK.0000000000001780
pii: 00024382-202111000-00011
pmc: PMC8518207
doi:
Substances chimiques
Biomarkers
0
Endothelial Protein C Receptor
0
Fibrin Fibrinogen Degradation Products
0
PROCR protein, human
0
RNA, Viral
0
fibrin fragment D
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
733-736Informations de copyright
Copyright © 2021 by the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Griffin JH, Lyden P. COVID-19 hypothesis: activated protein C for therapy of virus-induced pathologic thromboinflammation. Res Pract Thromb Haemost 4 (4):506–509, 2020.
Mazzeffi M, Chow JH, Amoroso A, Tanaka K. Revisiting the protein C pathway: an opportunity for adjunctive intervention in COVID-19? Anesth Analg 131 (3):690–693, 2020.
Maniatis NA, Letsiou E, Orfanos SE, Kardara M, Dimopoulou I, Nakos G, Lekka ME, Roussos C, Armaganidis A, Kotanidou A. Inhaled activated protein C protects mice from ventilator-induced lung injury. Crit Care 14 (2):R70, 2010.
Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci U S A 93 (19):10212–10216, 1996.
Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296 (5574):1880–1882, 2002.
Zheng X, Li W, Song Y, Hu Y, Ferrell GL, Esmon NL, Esmon CT. Non-hematopoietic EPCR regulates the coagulation and inflammatory responses during endotoxemia. J Thromb Haemost 5 (7):1394–1400, 2007.
Kurosawa S, Stearns-Kurosawa DJ, Carson CW, D’Angelo A, Della Valle P, Esmon CT. Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: lack of correlation with thrombomodulin suggests involvement of different pathological processes. Blood 91 (2):725–727, 1998.
Fukudome K, Kurosawa S, Stearns-Kurosawa DJ, He X, Rezaie AR, Esmon CT. The endothelial cell protein C receptor. Cell surface expression and direct ligand binding by the soluble receptor. J Biol Chem 271 (29):17491–17498, 1996.
Liaw PC, Neuenschwander PF, Smirnov MD, Esmon CT. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. J Biol Chem 275 (8):5447–5452, 2000.
Regan LM, Stearns-Kurosawa DJ, Kurosawa S, Mollica J, Fukudome K, Esmon CT. The endothelial cell protein C receptor. Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors. J Biol Chem 271 (29):17499–17503, 1996.
Saposnik B, Reny JL, Gaussem P, Emmerich J, Aiach M, Gandrille S. A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis. Blood 103 (4):1311–1318, 2004.
Uitte de Willige S, Van Marion V, Rosendaal FR, Vos HL, de Visser MC, Bertina RM. Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis. J Thromb Haemost 2 (8):1305–1310, 2004.
Martos L, Oto J, Fernández-Pardo A, Plana E, Solmoirago MJ, Cana F, Hervás D, Bonanad S, Ferrando F, España F, et al. Increase of neutrophil activation markers in venous thrombosis-contribution of circulating activated protein C. Int J Mol Sci 21 (16):5651, 2020.
Vassiliou AG, Kotanidou A, Mastora Z, Maniatis NA, Albani P, Jahaj E, Koutsoukou A, Armaganidis A, Orfanos SE. Elevated soluble endothelial protein C receptor levels at ICU admission are associated with sepsis development. Minerva Anestesiol 81 (2):125–134, 2015.
Vassiliou AG, Maniatis NA, Kotanidou A, Kallergi M, Karystinaki FS, Letsiou E, Glynos C, Kopterides P, Vassiliadi D, Nikitas N, et al. Endothelial protein C receptor polymorphisms and risk of severe sepsis in critically ill patients. Intensive Care Med 39 (10):1752–1759, 2013.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315 (8):801–810, 2016.
John S, Drobnik W, Lackner K, Schmieder RE. Soluble thrombomodulin and endothelial dysfunction in early atherosclerosis. Lancet 354 (9190):1647, 1999.
Xu J, Qu D, Esmon NL, Esmon CT. Metalloproteolytic release of endothelial cell protein C receptor. J Biol Chem 275 (8):6038–6044, 2000.
Stearns-Kurosawa DJ, Swindle K, D’Angelo A, Della Valle P, Fattorini A, Caron N, Grimaux M, Woodhams B, Kurosawa S. Plasma levels of endothelial protein C receptor respond to anticoagulant treatment. Blood 99 (2):526–530, 2002.
Saposnik B, Lesteven E, Lokajczyk A, Esmon CT, Aiach M, Gandrille S. Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma. Blood 111 (7):3442–3451, 2008.
Vassiliou AG, Kotanidou A, Mastora Z, Tascini C, Cardinali G, Orfanos SE. The H3 haplotype of the EPCR gene determines high sEPCR levels in critically ill septic patients. Infect Dis Ther 7: (suppl 1): 3–14, 2018.