ELEVATED P-SELECTIN IN SEVERE COVID-19: CONSIDERATIONS FOR THERAPEUTIC OPTIONS P-Selectine and COVID-19
Main Article Content
Keywords
P-selectin, Covid-19, Endothelium, Platelets
Abstract
BACKGROUND:
Coronavirus disease 2019 (COVID-19) is mainly a respiratory tract disease and acute respiratory failure with diffuse microvascular pulmonary thrombosis are critical aspects of the morbidity and mortality of this new syndrome.
PURPOSE:
The aim of our study was to investigate, in severe COVID-19 hospitalized patients, the P-selectin plasma concentration as a biomarker of endothelial dysfunction and platelet activation.
METHODS:
46 patients with severe or critical SARS-CoV-2 infection were included in the study. Age-matched patients then were divided in those requiring admission to the intensive care unit (ICU, ICU cases) vs those not requiring ICU hospitalization (non-ICU cases). Blood samples of severe COVID-19 patients were collected at the time of hospital admission. The quantification of soluble P-selectin was performed by ELISA assay.
RESULTS:
Our study showed a higher P-selectin plasma concentration in patients with Covid-19, regardless of ICU admission, compared to the normal reference values and compared to ten contextually sampled healthy donors (HD); (COVID-19): median 65.2 (IQRs: 45.1-81.1) vs. HD: 40.3 (IQRs: 24.3-48.7), p=0.0023). Moreover, results showed a significant reduction of P-selectin after platelets removal in HD, in contrast, both ICU and non-ICU COVID-19 patients showed similar high levels of P-selectin with and without platelets.
CONCLUSION:
Elevation of P-selectin suggests a central role of platelet endothelium interaction as part of the multifaced pathogenic mechanism of COVID-19 leading to the local activation of hemostatic system forming pulmonary thrombi. Further work is necessary to determine the therapeutic role of antiplatelets agents or of the anti P-selectin antibody Crizanlizumab.
Downloads
Abstract 1301
PDF Downloads 482
HTML Downloads 172
References
1. Guan WJ, Ni ZY, Hu Y, Liang WH, et al .:Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi:10.1056/NEJMoa2002032.
2. Hamming I, Timens W, Bulthuis ML, Lely AT et al.: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631-7.
3. Varga Z, Flammer AJ, Steiger P et al.: Endothelial cell infection and endotheliitis in
COVID-19. Lancet. 2020 May 2; 395(10234):1417-1418. doi: 10.1016/S0140-6736(20) 30937-5. Epub 2020 Apr 21.
4. Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of
therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019 Feb 28;133(9):906-918. doi: 10.1182/blood-2018-11-882993
5. Ivanov II, Apta BHR, Bonna AM, Harper MT. Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes. Sci Rep. 2019 Sep 16;9(1):13397. doi:
10.1038/s41598-019-49635-7.
6. Tan Li, Wang Qi, Zhang D. et al.: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020 Mar 27;5(1):33. doi: 10.1038/s41392-020-0148-4.
7. Zuo Y, Yalavarthi S, Shi H et al.: Neutrophil extracellular traps in COVID-19. JCI Insight. 2020 Apr 24. pii: 138999. doi: 10.1172/jci.insight.138999. [Epub ahead of print]
8. Du F, Jiang P, He S, Song D, Xu F. Antiplatelet Therapy for Critically Ill Patients: A
Pairwise and Bayesian Network Meta-Analysis. Shock. 2018 Jun;49(6):616-624.
9. Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and
transfusion-related acute lung injury. Blood. 2019 Apr 25;133(17):1840-1853
10. Blair HA. Crizanlizumab: First Approval. Drugs. 2020 Jan;80(1):79-84.