Variant-derived SARS-CoV-2 spike protein does not directly cause platelet activation or hypercoagulability

Area of Science:

• Virology
• Hematology
• Immunology

Background:

• Thrombosis is a known complication of COVID-19, linked to disease severity and mortality.
• The SARS-CoV-2 spike protein mediates viral entry into host cells.
• Direct effects of variant spike proteins on platelet function and coagulation remain largely unexamined.

Purpose of the Study:

• To investigate the direct impact of SARS-CoV-2 spike proteins from alpha, beta, gamma, and delta variants on platelet activity.
• To assess the influence of these spike proteins on blood coagulability.
• To determine if spike proteins directly induce platelet hyperactivity or hypercoagulability ex vivo.

Main Methods:

• An ethically approved ex vivo study using venous blood from 6 healthy subjects.
• Blood samples were exposed to spike proteins from SARS-CoV-2 variants (alpha, beta, gamma, delta) or no spike protein (control).
• Assessed platelet aggregability, P-selectin expression, PAC-1 binding, platelet count, mean platelet volume (MPV), and thromboelastography (TEG) parameters.

Main Results:

• No significant differences were observed in platelet aggregability across all tested variants compared to the control group.
• Spike proteins did not significantly alter P-selectin expression, PAC-1 binding, platelet count, MPV, or TEG parameters.
• Ex vivo exposure to 5 µg/ml of spike proteins from alpha, beta, gamma, and delta variants did not directly induce platelet hyperactivity or hypercoagulability.

Conclusions:

• The direct addition of SARS-CoV-2 variant spike proteins (alpha, beta, gamma, delta) at 5 µg/ml did not directly cause platelet hyperactivity or hypercoagulability in this ex vivo model.
• Findings suggest that other mechanisms may be responsible for the observed thrombotic events in COVID-19 patients.
• Further research is needed to elucidate the complex relationship between SARS-CoV-2 infection and thrombosis.