tetano
Editor, Senior Moderator
Cell Host Microbe
. 2020 Dec 26;S1931-3128(20)30679-X.
doi: 10.1016/j.chom.2020.12.016. Online ahead of print.
Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19
Qirui Guo[SUP] 1 [/SUP], Yingchi Zhao[SUP] 1 [/SUP], Junhong Li[SUP] 2 [/SUP], Jiangning Liu[SUP] 3 [/SUP], Xiuhong Yang[SUP] 3 [/SUP], Xuefei Guo[SUP] 1 [/SUP], Ming Kuang[SUP] 1 [/SUP], Huawei Xia[SUP] 1 [/SUP], Zeming Zhang[SUP] 1 [/SUP], Lili Cao[SUP] 1 [/SUP], Yujie Luo[SUP] 1 [/SUP], Linlin Bao[SUP] 3 [/SUP], Xiao Wang[SUP] 1 [/SUP], Xuemei Wei[SUP] 1 [/SUP], Wei Deng[SUP] 3 [/SUP], Nan Wang[SUP] 2 [/SUP], Luoying Chen[SUP] 1 [/SUP], Jingxuan Chen[SUP] 1 [/SUP], Hua Zhu[SUP] 3 [/SUP], Ran Gao[SUP] 3 [/SUP], Chuan Qin[SUP] 4 [/SUP], Xiangxi Wang[SUP] 5 [/SUP], Fuping You[SUP] 6 [/SUP]
Affiliations
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.
. 2020 Dec 26;S1931-3128(20)30679-X.
doi: 10.1016/j.chom.2020.12.016. Online ahead of print.
Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19
Qirui Guo[SUP] 1 [/SUP], Yingchi Zhao[SUP] 1 [/SUP], Junhong Li[SUP] 2 [/SUP], Jiangning Liu[SUP] 3 [/SUP], Xiuhong Yang[SUP] 3 [/SUP], Xuefei Guo[SUP] 1 [/SUP], Ming Kuang[SUP] 1 [/SUP], Huawei Xia[SUP] 1 [/SUP], Zeming Zhang[SUP] 1 [/SUP], Lili Cao[SUP] 1 [/SUP], Yujie Luo[SUP] 1 [/SUP], Linlin Bao[SUP] 3 [/SUP], Xiao Wang[SUP] 1 [/SUP], Xuemei Wei[SUP] 1 [/SUP], Wei Deng[SUP] 3 [/SUP], Nan Wang[SUP] 2 [/SUP], Luoying Chen[SUP] 1 [/SUP], Jingxuan Chen[SUP] 1 [/SUP], Hua Zhu[SUP] 3 [/SUP], Ran Gao[SUP] 3 [/SUP], Chuan Qin[SUP] 4 [/SUP], Xiangxi Wang[SUP] 5 [/SUP], Fuping You[SUP] 6 [/SUP]
Affiliations
- PMID: 33388094
- PMCID: PMC7762710
- DOI: 10.1016/j.chom.2020.12.016
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.