PMID- 37081872 OWN - NLM STAT- MEDLINE DCOM- 20230424 LR - 20230424 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19. PG - 1110874 LID - 10.3389/fimmu.2023.1110874 [doi] LID - 1110874 AB - INTRODUCTION: Tocilizumab, 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. METHODS: We 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. RESULTS: A 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-gamma(+) 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. CONCLUSION: There 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. CI - Copyright (c) 2023 Lee, Kim, Kang, Choe, Kim, Bang, Cho, Shin, Kim, Park and Oh. FAU - Lee, Chan Mi AU - Lee CM AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Minji AU - Kim M AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Anatomy & Cell Biology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kang, Chang Kyung AU - Kang CK AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Choe, Pyoeng Gyun AU - Choe PG AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Nam Joong AU - Kim NJ AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Bang, Hyeeun AU - Bang H AD - Research and development team 2, Molecular Diagnostics Division, Quantamatrix Inc., Seoul, Republic of Korea. FAU - Cho, Taeeun AU - Cho T AD - Research and development team 2, Molecular Diagnostics Division, Quantamatrix Inc., Seoul, Republic of Korea. FAU - Shin, Hyun Mu AU - Shin HM AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea. FAU - Kim, Hang-Rae AU - Kim HR AD - Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Anatomy & Cell Biology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea. AD - Medical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Park, Wan Beom AU - Park WB AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Oh, Myoung-Don AU - Oh MD AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230404 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Interleukin-6) RN - 0 (Cytokines) RN - 0 (HLA-DR Antigens) SB - IM MH - Humans MH - *CD8-Positive T-Lymphocytes MH - *COVID-19 MH - Interleukin-6 MH - Cytokines MH - HLA-DR Antigens PMC - PMC10110916 OTO - NOTNLM OT - IL-6 OT - T cell OT - critical COVID-19 OT - cytokine OT - immune response COIS- Author HB and TC are employed by QuantaMatrix. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/04/21 06:41 MHDA- 2023/04/24 06:41 PMCR- 2023/04/04 CRDT- 2023/04/21 02:14 PHST- 2022/11/29 00:00 [received] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/04/24 06:41 [medline] PHST- 2023/04/21 06:41 [pubmed] PHST- 2023/04/21 02:14 [entrez] PHST- 2023/04/04 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1110874 [doi] PST - epublish SO - Front Immunol. 2023 Apr 4;14:1110874. doi: 10.3389/fimmu.2023.1110874. eCollection 2023.