Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in t...

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Main Authors: Chan Mi Lee, Minji Kim, Chang Kyung Kang, Pyoeng Gyun Choe, Nam Joong Kim, Hyeeun Bang, Taeeun Cho, Hyun Mu Shin, Hang-Rae Kim, Wan Beom Park, Myoung-don Oh
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110874/full
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author Chan Mi Lee
Minji Kim
Minji Kim
Minji Kim
Chang Kyung Kang
Pyoeng Gyun Choe
Nam Joong Kim
Hyeeun Bang
Taeeun Cho
Hyun Mu Shin
Hyun Mu Shin
Hyun Mu Shin
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Wan Beom Park
Myoung-don Oh
author_facet Chan Mi Lee
Minji Kim
Minji Kim
Minji Kim
Chang Kyung Kang
Pyoeng Gyun Choe
Nam Joong Kim
Hyeeun Bang
Taeeun Cho
Hyun Mu Shin
Hyun Mu Shin
Hyun Mu Shin
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Wan Beom Park
Myoung-don Oh
author_sort Chan Mi Lee
collection DOAJ
description IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.
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spelling doaj.art-72eec1353a3c4883b12c5d5d6cd549df2023-04-04T05:32:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11108741110874Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19Chan Mi Lee0Minji Kim1Minji Kim2Minji Kim3Chang Kyung Kang4Pyoeng Gyun Choe5Nam Joong Kim6Hyeeun Bang7Taeeun Cho8Hyun Mu Shin9Hyun Mu Shin10Hyun Mu Shin11Hang-Rae Kim12Hang-Rae Kim13Hang-Rae Kim14Hang-Rae Kim15Hang-Rae Kim16Wan Beom Park17Myoung-don Oh18Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Anatomy & Cell Biology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaResearch and development team 2, Molecular Diagnostics Division, Quantamatrix Inc., Seoul, Republic of KoreaResearch and development team 2, Molecular Diagnostics Division, Quantamatrix Inc., Seoul, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaWide River Institute of Immunology, Seoul National University, Hongcheon, Republic of KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Anatomy & Cell Biology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaWide River Institute of Immunology, Seoul National University, Hongcheon, Republic of KoreaMedical Research Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaIntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110874/fullimmune responsecytokineIL-6T cellcritical COVID-19
spellingShingle Chan Mi Lee
Minji Kim
Minji Kim
Minji Kim
Chang Kyung Kang
Pyoeng Gyun Choe
Nam Joong Kim
Hyeeun Bang
Taeeun Cho
Hyun Mu Shin
Hyun Mu Shin
Hyun Mu Shin
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Hang-Rae Kim
Wan Beom Park
Myoung-don Oh
Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
Frontiers in Immunology
immune response
cytokine
IL-6
T cell
critical COVID-19
title Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
title_full Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
title_fullStr Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
title_full_unstemmed Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
title_short Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
title_sort different degree of cytokinemia and t cell activation according to serum il 6 levels in critical covid 19
topic immune response
cytokine
IL-6
T cell
critical COVID-19
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1110874/full
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