Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6 + effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of ‘immune silence’ in patients with critical COVID-19. Integrated studies of matched tissue sites and cell types in COVID-19 patients are important to define the immune mechanisms of pathology. Here, the authors describe an immune signature in fatal COVID-19 patients harmonizing single-cell RNA sequencing of blood and matched BAL cells with deep clinical, immunological and functional data.
【저자키워드】 SARS-CoV-2, viral infection, CD4-positive T cells, 【초록키워드】 COVID-19, Monocytes, Evolution, pathology, pandemic, severe COVID-19, Prognosis, severity, myeloid cells, lung, immune, Single-cell RNA sequencing, Clinical outcome, Regulatory, BAL, Features, Patient, disease, expression, Critical, immune mechanism, Blood, Immune suppression, Analysis, CXCR6, COVID-19 patient, dysregulation, cell type, Ex vivo, Activation, severe patients, tissue, blood sample, naïve, hallmark, impairment, fatal COVID-19, lymphoid, effector memory, immunological, feature, Cell, immune signature, characterized, functional, unique, to define, T cell subset, highlighting, lymphoid cell, single-cell RNA-seq analysis, tissue site, 【제목키워드】 immune, Patient, fatal COVID-19,