Реферат
The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders.
Тема - темы
COVID-19/pathology , Endothelium, Vascular/pathology , SARS-CoV-2 , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme 2/physiology , Animals , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Clinical Trials as Topic , Endothelial Cells/pathology , Endothelial Cells/virology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiopathology , HMGB1 Protein/physiology , Humans , Macaca mulatta , Mice , Neuropilin-1/physiology , Oxidative Stress , Reactive Oxygen Species , Receptors, Virus/physiology , Scavenger Receptors, Class B/physiology , Severity of Illness Index , Signal Transduction , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/physiopathology , Thrombophilia/etiology , Thrombophilia/physiopathology , Vascular Endothelial Growth Factor A/physiology , Vasculitis/etiology , Vasculitis/immunology , Vasculitis/physiopathology , Young AdultРеферат
SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.