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  • Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns #MMPMID34080738
  • Christensen EE; Jorgensen MJ; Nore KG; Dahl TB; Yang K; Ranheim T; Huse C; Lind A; Nur S; Stiksrud B; Jenum S; Tonby K; Holter JC; Holten AR; Halvorsen B; Dyrhol-Riise AM
  • J Intern Med 2021[Sep]; 290 (3): 677-692 PMID34080738show ga
  • BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naive CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.
  • |*Transcriptome[MESH]
  • |Adaptive Immunity[MESH]
  • |Adult[MESH]
  • |B-Lymphocytes/immunology[MESH]
  • |CD4-Positive T-Lymphocytes/immunology[MESH]
  • |CD8-Positive T-Lymphocytes/immunology[MESH]
  • |COVID-19/*genetics/*immunology[MESH]
  • |Female[MESH]
  • |HLA-DR Antigens/immunology[MESH]
  • |Humans[MESH]
  • |Immunity, Innate[MESH]
  • |Interleukin-2 Receptor alpha Subunit/immunology[MESH]
  • |Interleukin-7/immunology[MESH]
  • |Leukocyte L1 Antigen Complex/blood[MESH]
  • |Leukocytes, Mononuclear/*immunology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Monocytes/immunology[MESH]
  • |Phenotype[MESH]
  • |Programmed Cell Death 1 Receptor/immunology[MESH]
  • |SARS-CoV-2[MESH]
  • |Severity of Illness Index[MESH]
  • |T-Lymphocytes, Regulatory/immunology[MESH]
  • |Thromboplastin/immunology/metabolism[MESH]

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  • suck abstract from ncbi

    677 3.290 2021