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.
Subject(s)
Alarmins/pharmacology , Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Neutrophils/drug effects , SARS-CoV-2/drug effects , Animals , COVID-19/metabolism , COVID-19/virology , Disease Models, Animal , Female , Humans , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/metabolism , Transcriptome , Viral LoadABSTRACT
BACKGROUND The aim of this study was to understand the changes in psychological factors and sleep status of front-line medical staff in the fight against COVID-19 and provide evidence of exercise interventions to relieve psychological stress and improve sleep status for medical staff. MATERIAL AND METHODS A survey study was conducted among 120 front-line medical staff in the fight against COVID-19, of which 60 medical staff worked at the designated hospital (experimental group) and 60 medical staff worked at the non-designated hospital (control group). The Symptom Checklist 90 (SCL-90), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and PTSD Checklist-Civilian Version (PCL-C) were used to assess mental status. Sleep status was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS SCL-90 scores of somatization, depression, anxiety, and terror were higher than normal in front-line medical staff at the designated hospital. The SAS (45.89±1.117), SDS (50.13±1.813), and PCL-C (50.13±1.813) scores in the experimental group were higher than the normal control group, and were significantly different from those in the control group on SDS and PCL-C scales (P<0.05). The total average PSQI of the experimental group was 16.07±3.761, indicating that the sleep quality was poor. Among them, participants with moderate insomnia reached 61.67%, and participants with severe insomnia reached 26.67%. CONCLUSIONS There are psychological symptoms and sleep symptoms in front-line medical staff who participate in the fight against COVID-19, and they affect each other. Hospitals should improve emergency management measures, strengthen psychological counseling for clinical front-line medical staff, strengthen exercise intervention, and improve their sleep quality and mental health.