Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in 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 18th and May 5th , 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, CAD, 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 (VWF), and by the accumulation of plt-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 plt-EVs HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a six-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 co-receptor 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 haemostatic manifestations of the disease.