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Single-cell sequencing reveals the immune response mechanism of tortuzumab for effective treatment of severe neo-coronary pneumonia

At the beginning of the outbreak of neoconjunctivitis, Prof. Wei Haiming from the Department of Life Sciences and Medicine of USTC and Prof. Xu Xiaoling from the First Affiliated Hospital of USTC quickly formed a joint research team and proposed the "USTC protocol", which is a combination of conventional treatment with the traditional drug tolizumab, and started clinical trials.

Recently, Professor Qu Kun's team from the Department of Life Sciences and Medicine of the University of Science and Technology of China (USTC) published a paper titled "Single-cell analysis of two severe COVID-19 patients" in the journal Nature Communications. The study reveals a monocyte-associated and tocilizumab-responding cytokine storm", which reveals why tocilizumab is an effective treatment for severe neo-crown patients. Tocilizumab treatment attenuated the damage caused by the monocyte inflammatory factor storm while maintaining the normal antiviral immune response in neo-crown patients, providing the rationale for the "KUST solution.

In this study, the research team applied single-cell transcriptome sequencing (scRNA-seq) technology to analyze peripheral blood single nucleated cells from two severe neo-crown patients at the beginning of treatment and in remission, and found that a subpopulation of monocytes unique to severe neo-crown patients with high expression of inflammatory cytokine storm-related genes may be involved in mediating the inflammatory response of severe patients, while toltrezumab treatment significantly attenuated the inflammatory immune response of monocytes in patients.

In further studies, the team also identified important transcriptional regulators involved in the regulation of inflammatory cytokine storms, which may serve as potential drug targets for the treatment of the disease. In addition, the researchers also studied CD8+ T cells and B cells and found that the cellular immune response, represented by CD8+ T cells, and the humoral immune response, represented by B cells, were both increased to some extent after tolzumab treatment. The above results indicate that the treatment of severe neo-crown patients with tolizumab effectively attenuates the damage that the inflammatory cytokine storm may bring to the organism and helps the organism to maintain a high level of antiviral immune response, thus effectively treating the disease. This study provides a theoretical basis for the "KUSTECHU solution" for the treatment of severe neo-coronary infections.

Prof. Qu Kun, Professor of Life Science and Medicine, and Prof. Jun Lin and Prof. Tengchuan Jin of the research group of Prof. Qu's group are the co-corresponding authors of this paper, and Dr. Xing Guo and Bin Li, Special Research Associate of Prof. Qu's group, are the co-first authors. This work was supported by Prof. Hai-Ming Wei and Prof. Bin-Qing Fu at the Institute of Immunology, Chinese University of Science and Technology, and Prof. Lian-Xin Liu, Jian-Ping Weng and Xiaoling Ma at the First Affiliated Hospital of Chinese University of Science and Technology. This work was supported by the National Natural Science Foundation of China, the Key Research and Development Program of the Ministry of Science and Technology, and the "Emergency Science and Technology Tackling of Novel Coronavirus Infection" program of the Clinical Research Hospital of the Chinese Academy of Sciences (Hefei).