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. 2021 Jan 5;12(1):50.
doi: 10.1038/s41419-020-03333-9.

SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype

Affiliations

SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype

Dario Bongiovanni et al. Cell Death Dis. .

Abstract

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Activation marker expression in non-stimulated platelets.
Uniform manifold approximation and projection (UMAP) after equal random sampling from each sample and scaled, arcsinh-transformed expression [0–1] for each activation marker colored according to the expression level: A P-Selectin, B LAMP-3, and C LAMP-1, N = 8 COVID-19 patients, 11 healthy donors.
Fig. 2
Fig. 2. Marker expression in non-stimulated platelets.
Median signal intensity of activation markers (A) and relevant transmembrane proteins (B) in non-stimulated platelets. COVID-19 patients are plotted in red, whereas controls are plotted in blue. The horizontal line within the box plot represents the median, the top and bottom the interquartile range(Q1–Q3), whisker bars indicate the largest observation that is less than or equal to the upper inner fence (UIF = Q3 + 1.5 × IQR) or the smallest observation that is greater than or equal to the lower inner fence (LIF = Q1–1.5 × IQR) and the circles indicate outliers, if present; *P < 0.01. N = 8 COVID-19 patients, 11 healthy donors.
Fig. 3
Fig. 3. Marker expression in TRAP-stimulated platelets.
Median signal intensity of activation markers (A) and relevant transmembrane proteins (B) in TRAP-stimulated platelets (10 µM TRAP). COVID-19 patients are plotted in red, whereas controls are plotted in blue. The horizontal line within the box plot represents the median, the top and bottom the interquartile range (Q1–Q3), whisker bars indicate the largest observation that is less than or equal to the upper inner fence (UIF = Q3 + 1.5 × IQR) or the smallest observation that is greater than or equal to the lower inner fence (LIF = Q1–1.5 × IQR) and the circles indicate outliers, if present; *P < 0.01. N = 8 COVID-19 patients, 11 healthy donors.
Fig. 4
Fig. 4. Platelet reaction capacity.
Median signal intensity increase of activation marker expression after TRAP stimulation (10 µM) compared to non-stimulated platelets (baseline). Linear model analysis detected a reduced capacity of COVID-19 patients to increase expression of activation markers LAMP-3 and P-Selectin (p = 0.04 and p = 0.04) after TRAP stimulation. A P-Selectin, B LAMP-3, C LAMP-1. α: signal increment slope coefficient (for details see Methods); ns: nonsignificant. N = 8 COVID-19 patients, 11 healthy donors.

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