Chiara Agrati1, Veronica Bordoni1, Alessandra Sacchi1, Nicola Petrosillo1, Emanuele Nicastri1, Franca Del Nonno1, Gianpiero D’Offizi1, Fabrizio Palmieri1, Luisa Marchioni1, Maria Rosaria Capobianchi1, Andrea Antinori1, Giuseppe Ippolito1 and Michele Bibas1.
Received: September 17, 2020
Accepted: February 3, 2021
Mediterr J Hematol Infect Dis 2021, 13(1): e2021016 DOI 10.4084/MJHID.2021.016
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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.
COVID-19 is mainly a respiratory tract disease, and acute respiratory failure and diffuse microvascular pulmonary thrombosis are critical aspects of the morbidity and mortality of the coronavirus disease 2019 (Covid-19). However, both autopsy findings and clinical observations have described vascular damages and thrombotic complications in a wide range of organs.
Available published data suggest that from one-third to one-half of patients hospitalized with COVID-19 have hemostatic laboratory parameters suggestive of a pro-thrombotic state leading to a coagulopathy. These patients also manifest a hyperinflammatory state characterized by elevated inflammatory markers, strongly associated with severe pneumonia and a high mortality rate.
SARS-CoV-2 enters human cells by binding to the angiotensin-converting-enzyme 2 (ACE2) receptor, expressed on respiratory epithelial cells and other cell types, including endothelial cells.
Direct infection of endothelial cells, as well as the inflammatory environment, might result in an endothelial activation that drives the expression of P-selectin and tissue factor (TF), thus promoting platelet recruitment and aggregation. Subsequent accumulation of mononuclear cells provides a platform for the initiation of plasma coagulation by triggering prothrombin's cleavage to thrombin and fibrin formation.
The molecular interaction between P-selectin expressed in platelets and endothelial cells rapidly triggers TF exposure on monocytes, and this may represent a mechanism by which platelets and mononuclear cells contribute to disproportionate intravascular micro-thrombosis in SARS-CoV-2.
The aim of our study was to investigate, in COVID-19 hospitalized patients compared to healthy adult human controls, the ex-vivo P-selectin plasma concentration as a biomarker of endothelial dysfunction and platelet activation. The association between this parameter at the time of hospital admission and the severity and the outcomes of the disease with subsequent admittance into the intensive care unit (ICU) was finally assessed.
A group of ten age-matched healthy donors (HD) were enrolled in the study as controls. Characteristics of enrolled patients are described in Figure 1.
|Figure 1. The expression of P-selectin and Annexin V on platelet surface was evaluated in plasma samples by flow cytometry (A). The removal of platelets/vescicles in EV-free plasma samples was confirmed by flow cytometry (B).
Material and Methods
It will be interesting to examine whether therapies inhibiting platelet-endothelium interaction or inhibiting platelet function might improve microvascular perfusion, reduce thrombo-inflammation, and finally reduce COVID-19 morbidity and mortality.
In this perspective, we suggest studying, in the early phases of COVID-19 disease, the role of anti-platelet agents, acetylsalicylic acid, GPIIb, GPIIIa antagonists, and P2Y12 antagonists, not only in de novo therapy initiation but also in patients previously in prophylaxis or in treatment for cardiovascular disorders. The suggested mechanism to study is not only the direct P-selectin/platelet interaction but also the neutrophil extracellular trap (NET) production as described in sepsis and transfusion-related acute lung injury (TRALI).[9,10,11] Further, Crizanlizumab-tmca, a selectin blocker humanized IgG2 kappa monoclonal antibody that binds to P-selectin, and approved to reduce the frequency of vasoocclusive crises (VOCs) in adult and pediatric patients, might be evaluated in severe cases not responding or in combination to anti-platelet therapy.[12,13]
We gratefully acknowledge the Collaborators Members of INMI COVID-19 study group: Maria Alessandra Abbonizio, Amina Abdeddaim, Chiara Agrati, Fabrizio Albarello, Gioia Amadei, Alessandra Amendola, Mario Antonini, Tommaso Ascoli Bartoli, Francesco Baldini, Raffaella Barbaro, Bardhi Dorian, Barbara Bartolini, Rita Bellagamba, Martina Benigni, Nazario Bevilacqua, Gianlugi Biava, Michele Bibas, Licia Bordi, Veronica Bordoni, Evangelo Boumis, Marta Branca, Donatella Busso, Marta Camici, Paolo Campioni, Maria Rosaria Capobianchi, Alessandro Capone, Cinzia Caporale, Emanuela Caraffa, Ilaria Caravella, Fabrizio Carletti, Concetta Castilletti, Adriana Cataldo, Stefano Cerilli, Carlotta Cerva, Roberta Chiappini, Pierangelo Chinello, Carmine Ciaralli, Stefania Cicalini, Francesca Colavita, Angela Corpolongo, Massimo Cristofaro, Salvatore Curiale, Alessandra D’Abramo, Cristina Dantimi, Alessia De Angelis, Giada De Angelis, Maria Grazia De Palo, Federico De Zottis, Virginia Di Bari, Rachele Di Lorenzo, Federica Di Stefano, Gianpiero D’Offizi, Davide Donno, Francesca Faraglia, Federica Ferraro, Lorena Fiorentini, Andrea Frustaci, Matteo Fusetti, Vincenzo Galati, Roberta Gagliardini, Paola Gallì, Gabriele Garotto, Saba Gebremeskel Tekle, Maria Letizia Giancola, Filippo Giansante, Emanuela Giombini, Guido Granata, Maria Cristina Greci, Elisabetta Grilli, Susanna Grisetti, Gina Gualano, Fabio Iacomi, Giuseppina Iannicelli, Giuseppe Ippolito, Eleonora Lalle, Simone Lanini, Daniele Lapa, Luciana Lepore, Raffaella Libertone, Raffaella Lionetti, Giuseppina Liuzzi, Laura Loiacono, Andrea Lucia, Franco Lufrani, Manuela Macchione, Gaetano Maffongelli, Alessandra Marani, Luisa Marchioni, Raffaella Marconi, Andrea Mariano, Maria Cristina Marini, Micaela Maritti, Alessandra Mastrobattista, Giulia Matusali, Valentina Mazzotta, Paola Mencarini, Silvia Meschi, Francesco Messina, Annalisa Mondi, Marzia Montalbano, Chiara Montaldo, Silvia Mosti, Silvia Murachelli, Maria Musso, Emanuele Nicastri, Pasquale Noto, Roberto Noto, Alessandra Oliva, Sandrine Ottou, Claudia Palazzolo, Emanuele Pallini, Fabrizio Palmieri, Carlo Pareo, Virgilio Passeri, Federico Pelliccioni, Antonella Petrecchia, Ada Petrone, Nicola Petrosillo, Elisa Pianura, Carmela Pinnetti, Maria Pisciotta, Silvia Pittalis, Agostina Pontarelli, Costanza Proietti, Vincenzo Puro, Paolo Migliorisi Ramazzini, Alessia Rianda, Gabriele Rinonapoli, Silvia Rosati, Martina Rueca, Alessandra Sacchi, Alessandro Sampaolesi, Francesco Sanasi, Carmen Santagata, Alessandra Scarabello, Silvana Scarcia, Vincenzo Schininà, Paola Scognamiglio, Laura Scorzolini, Giulia Stazi, Fabrizio Taglietti, Chiara Taibi, Roberto Tonnarini, Simone Topino, Francesco Vaia, Francesco Vairo, Maria Beatrice Valli, Alessandra Vergori, Laura Vincenzi, Ubaldo Visco-Comandini, Pietro Vittozzi, Mauro Zaccarelli.
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