1. Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.
- Author
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Christensen EE, Jørgensen 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, and Dyrhol-Riise AM
- Subjects
- Adaptive Immunity, Adult, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Female, HLA-DR Antigens immunology, Humans, Immunity, Innate, Interleukin-2 Receptor alpha Subunit immunology, Interleukin-7 immunology, Leukocyte L1 Antigen Complex blood, Male, Middle Aged, Monocytes immunology, Phenotype, Programmed Cell Death 1 Receptor immunology, SARS-CoV-2, Severity of Illness Index, T-Lymphocytes, Regulatory immunology, Thromboplastin immunology, Thromboplastin metabolism, COVID-19 genetics, COVID-19 immunology, Leukocytes, Mononuclear immunology, Transcriptome
- Abstract
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 naïve 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., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)
- Published
- 2021
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