AUTHOR=Lee Chan Mi , Kim Minji , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Bang Hyeeun , Cho Taeeun , Shin Hyun Mu , Kim Hang-Rae , Park Wan Beom , Oh Myoung-don 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1110874

DOI=10.3389/fimmu.2023.1110874

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>A total of nine patients with critical COVID-19 were included. The high (<italic>n</italic> = 5) and low IL-6 (<italic>n</italic> = 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<sup>+</sup>CD16<sup>+</sup>), IFN-γ<sup>+</sup> CD4<sup>+</sup> or CD8<sup>+</sup> T cells, and HLA-DR<sup>+</sup>PD-1<sup>+</sup> CD4<sup>+</sup> T cells were higher in the high IL-6 group than in the low IL-6 group.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>