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Eur Cytokine Netw . Th1 cytokine endotype discriminates and predicts severe complications in COVID-19

tetano

Editor, Senior Moderator
Eur Cytokine Netw


. 2022 Jun 1;33(2):1-12.
doi: 10.1684/ecn.2022.0477.
Th1 cytokine endotype discriminates and predicts severe complications in COVID-19


Takehiro Hasegawa[SUP] 1 [/SUP], Takashi Hato[SUP] 2 [/SUP], Toshitsugu Okayama[SUP] 3 [/SUP], Kazuho Ikeo[SUP] 3 [/SUP], Yoshiaki Miyamoto[SUP] 4 [/SUP], Niina Iwanaga[SUP] 4 [/SUP], Kohjin Suzuki[SUP] 5 [/SUP], Maho Yoshida[SUP] 6 [/SUP], Kazuto Yamashita[SUP] 4 [/SUP], Saya Yamashita[SUP] 7 [/SUP], Eiya Tamada[SUP] 4 [/SUP], Abdullah Khasawneh[SUP] 8 [/SUP], Faith Jessica Paran[SUP] 9 [/SUP], Rieko Oyama[SUP] 9 [/SUP], Toshio Naito[SUP] 9 10 [/SUP], Kenta Noda[SUP] 11 [/SUP], Yoko Tabe[SUP] 8 9 [/SUP]



Affiliations

Abstract

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.

Keywords: COVID-19; Th1 inflammation; T cell exhaustion.
 
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