Th1 cytokine endotype discriminates and predicts severe complications in COVID-19

• Published in: European cytokine network Vol. 33; no. 2; pp. 25 - 12
• Main Authors: Hasegawa, Takehiro, Hato, Takashi, Okayama, Toshitsugu, Ikeo, Kazuho, Miyamoto, Yoshiaki, Iwanaga, Niina, Suzuki, Kohjin, Yoshida, Maho, Yamashita, Kazuto, Yamashita, Saya, Tamada, Eiya, Khasawneh, Abdullah, Paran, Faith Jessica, Oyama, Rieko, Naito, Toshio, Noda, Kenta, Tabe, Yoko
• Format: Journal Article
• Language: English
• Published: France Springer Nature B.V 01.06.2022; John Libbey Eurotext
• Subjects: Biomarkers; C-Reactive Protein; CCL17 protein; Cell-mediated immunity; Chemokines; Coronaviruses; COVID-19; Cytokines; Effector cells; Humans; Inflammation; Interleukin 10; Interleukin 18; Interleukin 6; Leukocytes, Mononuclear; Lymphocytes T; Pathology; Patients; Peripheral blood mononuclear cells; Public health; COVID-19; T cell exhaustion; Th1 inflammation
• ISSN: 1148-5493; 1952-4005
• DOI: 10.1684/ecn.2022.0477

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.