Background: SARS-CoV-2 infection causing COVID-19 is associated with a high incidence of thrombotic complications, a phenomenon in which platelets play an important contributory role. COVID-19 is associated with alterations in platelet function, including increased platelet-neutrophil aggregates and impaired integrin αIIbβ3 activation. The mechanisms underlying such effects remain unclear.

Aims: In this study, we aimed to identify changes in the platelet proteome in patients with COVID-19 and explore implicated biological pathways.

Methods: Patients hospitalized with COVID-19 (N&#3f7) and healthy controls (N&#3f6) were recruited between October 2020 and February 2021. Proteomics analysis was performed on washed platelets using Tandem Mass Tag Mass Spectrometry (TMT-MS). Alterations in platelet proteins were analyzed using Gene Ontology (GO) pathways.

Results: A total of 5773 proteins were quantified in COVID-19 patients and controls. There was differential expression of 858 (15%) proteins between patients with severe COVID-19 infection and controls (false discovery rate p < 0.05). Pathway analysis revealed expression changes in gene products associated with regulation of platelet activation (GO:0010543), with reduced expression of platelet kinases (PRKCA, PRKCD, PRKCQ, LYN, SYK and JAK2), glycoproteins (GP5 and GP9) and PLEK, known positive regulators of integrin activation. There was increased expression of alpha- and dense-granule lumen gene products (GO:0031093 and GO:0031089), including protease inhibitors SERPINA3, SERPING1 and SERPINF2.

Conclusion(s): Our results demonstrate diverse changes in signaling and secretion pathways important to platelet activity in patients hospitalized with COVID-19. Increased abundance of platelet granule proteins is in keeping with published plasma proteome descriptions, suggesting platelet uptake of plasma proteins. Platelet granule proteins involved in the regulation of hemostasis may contribute to the increased risk of thrombosis seen in this patient cohort and point towards potential therapeutic targets for COVID-19 related thrombotic complications.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/exploring-platelet-proteins-altered-in-severe-covid-19-using-gene-ontology-go-pathways/