The Journal of Clinical Investigation (Feb 2022)

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

  • Tianyang Li,
  • Yang Yang,
  • Yongqi Li,
  • Zhengmin Wang,
  • Faxiang Ma,
  • Runqi Luo,
  • Xiaoming Xu,
  • Guo Zhou,
  • Jianhua Wang,
  • Junqi Niu,
  • Guoyue Lv,
  • Ian N. Crispe,
  • Zhengkun Tu

Journal volume & issue
Vol. 132, no. 4

Abstract

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Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.

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