Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19

J Thromb Haemost. 2022 Feb;20(2):434-448. doi: 10.1111/jth.15575. Epub 2021 Nov 16.

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.

Keywords: COVID-19; HMGB1; P-selectin; SARS-CoV-2; platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets
  • COVID-19*
  • Humans
  • Platelet Activation
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2