Role of LL-37 in thrombotic complications in patients with COVID-19

Author:

Duan Zilei,Zhang Juan,Chen Xue,Liu Ming,Zhao Hongwen,Jin Lin,Zhang Zhiye,Luan Ning,Meng Ping,Wang Jing,Tan Zhaoxia,Li Yaxiong,Deng Guohong,Lai RenORCID

Abstract

AbstractBlood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Funder

Chinese Academy of Sciences

National Natural Science Foundation of China

Yunnan Provincial Science and Technology Department

PLA Youth Talent Project

Chongqing Science and Technology Commission

Yunnan Provincial Postdoctoral Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Cellular and Molecular Neuroscience,Pharmacology,Molecular Biology,Molecular Medicine

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