SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management. Infection with SARS-CoV-2 results in activation of multiple immune cell types in situ but also in the peripheral blood compartment. Here the authors apply single cell sequencing and machine learning to characterise the response and link this to confer prognostic indicators in critically ill COVID-19 patients.
【저자키워드】 SARS-CoV-2, viral infection, Applied immunology, Pathogens, 【초록키워드】 COVID-19, Monocytes, Mortality, antibody, transcriptomics, Infection, interferon, cell cycle, Single-cell RNA sequencing, monocyte, Peripheral blood, risk stratification, survival, single cell sequencing, Critically ill, Accuracy, cells, pathway, Clinical management, interferon signaling, Single Cell, dataset, predictor, Antigen presentation, Critical, predict, mechanism, COVID-19 patients, Blood, CD16, Differential gene expression, Immune cell, framework, Trigger, critically ill COVID-19 patients, triggers, mononuclear cells, cell types, cell type, transcriptomes, systemic immune response, Activation, Regulation, complex, sequence, CD14, circulating, machine, critical COVID-19 patients, identifying, prognostic indicator, Cell, independent, transcriptional, identify, promote, critical COVID-19 patient, immune cell type, NK-cell, 【제목키워드】 peripheral immune response, survival, predict, critical COVID-19 patient,