Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A hi /HLA-DR lo classical monocytes and activated LAG-3 hi T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8 + clones, unmutated IGHG + B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19. SARS-CoV-2 infection can lead to progressive pathology in patients with COVID-19, but information for this disease progression is sparse. Here the authors use multi-omics approach to profile the immune responses of patients, assessing immune repertoire and effects of tocilizumab treatments, to find a dyssynchrony between innate and adaptive immunity in progressive COVID-19.
【저자키워드】 SARS-CoV-2, viral infection, cellular immunity, Systems analysis, 【초록키워드】 COVID-19, Monocytes, pathology, immune response, Gene Expression, adaptive, severe COVID-19, Immunity, Tocilizumab, T cells, SARS-COV-2 infection, SARS-CoV-2 virus, immunopathology, hospitalized patients, CD8, immune, B cell, Disease progression, Protein, T cell, immune responses, immune profiling, Lineage, information, T cell receptor, patients, single-cell, marker, cellular, Interaction, Frequency, Analysis, dysregulated immune response, innate and adaptive immunity, classical monocytes, progressive disease, clones, hallmark, dysregulated immune responses, clone, hallmarks, progressive COVID-19, probe, LAG-3, Effect, approach, Cell, highlight, immune signature, Course, activated, hospitalized patient, mutated, reveal, classical monocyte, patients with COVID-19, skewed, the SARS-CoV-2 virus, 【제목키워드】 adaptive immune system, reveal,