AI Article Synopsis
- The SARS-CoV-2 pandemic is a significant public health threat, causing disruptions in the immune system.
- Researchers studied the immune responses in animal models and found that the S100A8 alarmin was strongly elevated in both infected animals and COVID-19 patients.
- Treatment with Paquinimod, an inhibitor of S100A8/A9, showed promise in reducing viral loads, enhancing survival rates in infected mice, and regulating harmful neutrophils, thereby opening new avenues for COVID-19 treatments.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762710 | PMC |
| http://dx.doi.org/10.1016/j.chom.2020.12.016 | DOI Listing |
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