Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein

Area of Science:

• Immunology
• Hematology
• Virology

Background:

• Severe COVID-19 is associated with hemostasis disorders and cytokine storms.
• The precise mechanisms linking these severe manifestations remain unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms by which SARS-CoV-2 infection leads to severe COVID-19 pathology.
• To identify potential therapeutic targets for mitigating severe COVID-19 outcomes.

Main Methods:

• Investigated the interaction between SARS-CoV-2 spike protein and platelet receptor CD42b.
• Analyzed platelet-monocyte communication pathways involving P-selectin/PSGL-1 and CD40L/CD40.
• Assessed the impact on proinflammatory cytokine production by monocytes.

Main Results:

• SARS-CoV-2 spike protein activates platelets through CD42b via two distinct signaling pathways.
• Activated platelets promote monocyte activation and proinflammatory cytokine release.
• Established a link between platelet activation, monocyte communication, and cytokine storm in severe COVID-19.

Conclusions:

• The findings explain the correlation between hypercoagulation, monocyte activation, and cytokine storm in severe COVID-19.
• Targeting the identified spike protein-receptor interactions may offer a therapeutic strategy.