Platelet activation and thrombotic events characterizes COVID-19.
Background: Platelet activation and thrombotic events characterizes COVID-19. Objectives: To characterize platelet activation and determine if SARS-CoV-2 induces platelet activation. Patients/Methods: We investigated platelet activation in 119 COVID-19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. Results: COVID-19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet-derived (plt) extracellular vesicles (EVs) and HMGB1+ plt-EVs in the plasma. P-selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P-selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6-point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS-CoV-2 underwent activation, which was replicated using SARS-CoV-2 pseudo-viral particles and purified recombinant SARS-CoV-2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS-CoV-2, and Spike-dependent platelet activation, aggregation and granule release, release of soluble P-selectin and HMGB1+ plt-EVs abated in the presence of anti-CD147 antibodies. Conclusions: Hence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS-CoV-2, characterizes COVID-19 and could contribute to the inflammatory and hemostatic manifestations of the disease.
Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19 / Maugeri, Norma; De Lorenzo, Rebecca; Clementi, Nicola; Diotti, Roberta Antonia; Criscuolo, Elena; Godino, Cosmo; Tresoldi, Cristina; Bonini, Chiara; Clementi, Massimo; Mancini, Nicasio; Ciceri, Fabio; Rovere-Querini, Patrizia; Manfredi, Angelo A. - In: JOURNAL OF THROMBOSIS AND HAEMOSTASIS. - ISSN 1538-7933. - 20:20(2)(2022), pp. 434-448. [10.1111/jth.15575]
Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19
De Lorenzo, Rebecca;Clementi, Nicola;Diotti, Roberta Antonia;Criscuolo, Elena;Bonini, Chiara;Clementi, Massimo;Mancini, Nicasio;Ciceri, Fabio;Rovere-Querini, Patrizia;Manfredi, Angelo A
2022-01-01
Abstract
Background: Platelet activation and thrombotic events characterizes COVID-19. Objectives: To characterize platelet activation and determine if SARS-CoV-2 induces platelet activation. Patients/Methods: We investigated platelet activation in 119 COVID-19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. Results: COVID-19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet-derived (plt) extracellular vesicles (EVs) and HMGB1+ plt-EVs in the plasma. P-selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P-selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6-point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS-CoV-2 underwent activation, which was replicated using SARS-CoV-2 pseudo-viral particles and purified recombinant SARS-CoV-2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS-CoV-2, and Spike-dependent platelet activation, aggregation and granule release, release of soluble P-selectin and HMGB1+ plt-EVs abated in the presence of anti-CD147 antibodies. Conclusions: Hence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS-CoV-2, characterizes COVID-19 and could contribute to the inflammatory and hemostatic manifestations of the disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.