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Th1 cytokine endotype discriminates and predicts severe complications in COVID-19 Volume 33, numéro 2, 2022-06-01

Illustrations


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Tableaux

Auteurs
1 Research and Development Division, Sysmex R&D Centre Europe GmbH, Falkenried 88 20251 Hamburg, Germany,
2 Division of Nephrology, Indiana University, 107 S Indiana Ave, Bloomington, USA
3 Center for Information Biology, National Institute of Genetics, 1111 Yata, Mishima, Sizuoka, Japan
4 Central Research Laboratories, Sysmex Corporation, 4-4-4, Takatsuka-dai, Nish Ward, Kobe, Japan
5 System Technology Laboratories, Sysmex Corporation, 4-4-4, Takatsuka-dai, Nish Ward, Kobe, Japan
6 Scientific Affairs, Sysmex Corporation, Division 1-3-2, Murotani, Nish Ward, Kobe, Japan
7 Business Incubation Department, Sysmex Corporation, 4-4-4, Takatsuka-dai, Nish Ward, Kobe, Japan
8 Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo Ward, Tokyo, Japan
9 Department of Research Support Utilizing Bioresource Bank, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo Ward, Tokyo, Japan
10 Department of General Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo Ward, Tokyo, Japan
11 Reagent Engineering Department, Sysmex Corporation 4-4-4, Takatsuka-dai, Nish Ward, Kobe, Japan
Correspondence: T. Hasegawa

Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.