Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation

Abstract

Platelets are central elements of hemostasis and also play a pivotal role in the pathogenesis of thrombosis in coronavirus disease 2019. This study was planned to investigate the effects of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant spike protein variants on platelet morphology and activation. Citrated whole blood collected from ostensibly healthy subjects was challenged with saline (control sample) and with 2 and 20 ng/mL final concentration of SARS-CoV-2 recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Platelet count was found to be decreased with all SARS-CoV-2 recombinant spike protein variants and concentrations tested, achieving the lowest values with 20 ng/mL Delta recombinant spike protein. The mean platelet volume increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, but especially using Delta and Alpha recombinant spike proteins. The values of both platelet function analyzer-200 collagen-adenosine diphosphate and collagen-epinephrine increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, and thus reflecting platelet exhaustion, and displaying again higher increases with Delta and Alpha recombinant spike proteins. Most samples where SARS-CoV-2 recombinant spike proteins were added were flagged as containing platelet clumps. Morphological analysis revealed the presence of a considerable number of activated platelets, platelet clumps, platelet-monocyte, and platelet-neutrophils aggregates, especially in samples spiked with Alpha and Delta recombinant spike proteins at 20 ng/mL. These results provide support to the evidence that SARS-CoV-2 is capable of activating platelets through its spike protein, though such effect varies depending on different spike protein variants.

Editorial Compilation XIV

“…The last full-length paper in this issue is an original study on the effects of recombinant SARS-CoV-2 spike protein variants on platelet morphology and activation, from the team of Vettori and colleagues. 12 As our readership well understands, platelets represent central elements of hemostasis and also play a pivotal role in the pathogenesis of COVID-19 thrombosis. The current study was planned to investigate the effects of different SARS-CoV-2 recombinant spike protein variants on platelet morphology and activation.…”

Description of an In Vitro Platelet Function Analyzer (PFA-100/PFA-200) 30 Years in the Making

“…We still, in 2024, use the PFA-100/-200 primarily to screen for VWD, with updated findings published in 2020, 42 or else to monitor desmopressin therapy in VWD. 43 The instruments may be used for a variety of different purposes in other laboratories, for example as a preoperative screen, 44 to evaluate platelet function in animals, 45 to evaluate effects of coronavirus disease 2019 spike protein on platelet function, 46 to evaluate drug effects on platelet function, 47,48 to evaluate the effect of recombinant von Willebrand factor (VWF) on prolonged PFA closure times in extracorporeal membrane oxygenation patients with acquired von Willebrand syndrome, 49 to monitor antiplatelet therapy, 50 as a measure of platelet function in blood donors, 51 and as a potential marker of thrombosis risk, 52 just to name a few potential uses.…”