1. Academic Validation
  2. Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19

Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19

  • Cell Host Microbe. 2021 Feb 10;29(2):222-235.e4. doi: 10.1016/j.chom.2020.12.016.
Qirui Guo 1 Yingchi Zhao 1 Junhong Li 2 Jiangning Liu 3 Xiuhong Yang 3 Xuefei Guo 1 Ming Kuang 1 Huawei Xia 1 Zeming Zhang 1 Lili Cao 1 Yujie Luo 1 Linlin Bao 3 Xiao Wang 1 Xuemei Wei 1 Wei Deng 3 Nan Wang 2 Luoying Chen 1 Jingxuan Chen 1 Hua Zhu 3 Ran Gao 3 Chuan Qin 4 Xiangxi Wang 5 Fuping You 6
Affiliations

Affiliations

  • 1 Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
  • 2 University of Chinese Academy of Sciences, CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.
  • 4 Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China. Electronic address: qinchuan@pumc.edu.cn.
  • 5 University of Chinese Academy of Sciences, CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: xiangxi@ibp.ac.cn.
  • 6 Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China. Electronic address: fupingyou@hsc.pku.edu.cn.
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 Infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus Infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus Infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.

Keywords

Paquinimod; S100A8/A9; SARS-CoV-2; aberrant neutrophils.

Figures
Products