Platelet gene expression and function in patients with COVID-19.

Area of Science:

• Hematology
• Virology
• Immunology

Background:

• Thrombotic complications are a major cause of mortality in COVID-19.
• Platelet function alterations in COVID-19 pathophysiology are not well understood.
• Severe COVID-19 presents with hemostatic abnormalities, but the role of platelets is unclear.

Purpose of the Study:

• To investigate the impact of SARS-CoV-2 infection on platelet gene expression and function.
• To determine if platelets contribute to the thrombotic complications observed in COVID-19 patients.

Main Methods:

• RNA sequencing of circulating platelets from COVID-19 patients and healthy donors.
• Analysis of platelet gene-expression profiles and associated pathways.
• Assessment of platelet activation markers (e.g., P-selectin), aggregation, and cell-cell aggregate formation.
• Detection of SARS-CoV-2 genetic material in platelets.

Main Results:

• COVID-19 platelets showed distinct gene-expression changes, including in pathways related to protein ubiquitination, antigen presentation, and mitochondrial dysfunction.
• SARS-CoV-2 mRNA was detected in platelets, independent of ACE2 receptor expression.
• Platelets from COVID-19 patients exhibited increased basal and activation-induced P-selectin expression.
• Elevated levels of circulating platelet aggregates with neutrophils, monocytes, and T-cells were observed.
• COVID-19 platelets displayed enhanced aggregation and spreading, partly due to increased MAPK pathway activation and thromboxane generation.

Conclusions:

• SARS-CoV-2 infection induces platelet hyperreactivity.
• Altered platelet function and increased aggregation may contribute to the pathophysiology of COVID-19, including thrombotic events.
• Platelets are a potential key player in COVID-19-associated organ damage and mortality.