PDF(Pubmed)
Abstract：
As a disease causing a global pandemic, the progression of symptoms to severe disease in patients with COVID-19 often has adverse outcomes, but research on the immunopathology of COVID-19 severe disease remains limited. In this study, we used mRNA-seq data from the peripheral blood of COVID-19 patients to identify six COVID-19 severe immune characteristic genes (FPR1, FCGR2A, TLR4, S100A12, CXCL1, and L TF), and found neutrophils to be the critical immune cells in COVID-19 severe disease. Subsequently, using scRNA-seq data from bronchoalveolar lavage fluid from COVID-19 patients, neutrophil subtypes highly expressing the S100A family were found to be located at the end of cellular differentiation and tended to release neutrophil extracellular traps. Finally, it was also found that alveolar macrophages, macrophages, and monocytes with a high expression of COVID-19 severe disease immune characteristic genes may influence neutrophils through intercellular ligand-receptor pairs to promote neutrophil extracellular trap release. This study provides immune characteristic genes, critical immune pathways, and immune cells in COVID-19 severe disease, explores intracellular immune transitions of critical immune cells and pit-induced intercellular communication of immune transitions, and provides new biomarkers and potential drug targets for the treatment of patients with COVID-19 severe disease.
摘要：
作为一种引起全球大流行的疾病，COVID-19患者症状进展为严重疾病通常会有不良结局，但对COVID-19严重疾病的免疫病理学研究仍然有限。在这项研究中,我们使用来自COVID-19患者外周血的mRNA-seq数据来鉴定六个COVID-19严重免疫特征基因(FPR1，FCGR2A，TLR4、S100A12、CXCL1和LTF)，并发现中性粒细胞是COVID-19严重疾病的关键免疫细胞。随后，使用来自COVID-19患者支气管肺泡灌洗液的scRNA-seq数据，发现高表达S100A家族的中性粒细胞亚型位于细胞分化的末端，并倾向于释放中性粒细胞胞外陷阱。最后,还发现肺泡巨噬细胞，巨噬细胞，高表达COVID-19重症疾病免疫特征基因的单核细胞可能通过细胞间配体-受体对影响中性粒细胞，促进中性粒细胞胞外诱捕网释放。这项研究提供了免疫特征基因，关键的免疫途径，和COVID-19严重疾病中的免疫细胞，探索关键免疫细胞的细胞内免疫转换和坑诱导的免疫转换的细胞间通讯，并为COVID-19重症患者的治疗提供了新的生物标志物和潜在的药物靶标。
