RNA-seq of platelets from SARS-CoV-2 Covid-19
There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are associated with increased mortality. Many patients with severe COVID-19 present with hemostatic abnormalities that mimic other systemic coagulopathies associated with severe infections and platelet dysfunction. However, if SARS-COV2 infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and platelet function in patients infected with SARS-COV2. RNA sequencing of circulating platelets demonstrated distinct changes in the gene expression profile of COVID-19 patients. Pathway analysis revealed differential gene expression changes in pathways associated with protein ubiquitination, antigen presentation and mitochondrial dysfunction. Surprisingly, mRNA from the SARS-COV2 N1 gene was detected in platelets from several COVID-19 patients. Interestingly, neither ACE2 mRNA nor protein was detected in platelets, indicating platelets take-up SARS-COV2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared to healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. Finally, COVID-19 patients had reduced procoagulant platelet responses which were associated with altered mitochondrial function. These findings demonstrate that SARS-COV2 impacts platelet function which may contribute to the increased thrombotic phenotype observed in COVID-19 patients