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

  • J Clin Invest. 2022 Feb 15;132(4):e150101. doi: 10.1172/JCI150101.
Tianyang Li  1 ,  Yang Yang  1 ,  Yongqi Li  1 ,  Zhengmin Wang  1 ,  Faxiang Ma  1 ,  Runqi Luo  2 ,  Xiaoming Xu  2 ,  Guo Zhou  2 ,  Jianhua Wang  3 ,  Junqi Niu  4 ,  Guoyue Lv  4 ,  Ian N Crispe  5 ,  Zhengkun Tu  1  4
Affiliations
  • 1. Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
  • 2. Department of Infectious Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 3. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
  • 4. Institute of Liver Diseases, The First Hospital of Jilin University, Changchun, Jilin, China.
  • 5. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
PMID: 34964720 DOI: 10.1172/JCI150101
Abstract

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.

Keywords
COVID-19; Inflammation; Monocytes; Platelets.
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