Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus

Yonggang Zhou; Binqing Fu; Xiaohu Zheng; Dongsheng Wang; Changcheng Zhao; Yingjie qi; Rui Sun; Zhigang Tian; Xiaoling Xu; Haiming Wei

Hubei province, China 3-5 , which was also named as pneumonia-associated respiratory 24 syndrome (PARS) 6 . Up to 9th of February 2020, at least 37, 251 cases have been reported 25 with 812 fatal cases according to the report from China CDC. However, the immune 26 mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still 27 unknown. Here we show that after the 2019-nCoV infection, CD4 + T lymphocytes are rapidly 28 activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc. The cytokines 29 environment induces inflammatory CD14 + CD16 + monocytes with high expression of IL-6 and 30 accelerates the inflammation. These aberrant and excessive immune cells may enter the 31 pulmonary circulation in huge numbers and play an immune damaging role to causing lung 32 functional disability and quick mortality. Our results demonstrate that excessive non-effective 33 host immune responses by pathogenic T cells and inflammatory monocytes may associate 34 with severe lung pathology. Therefore, we suggest that monoclonal antibody that targets the 35 GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 36 2019-nCoV and consequently win more time for virus clearance. with 2019-nCoV, that have been reported recently, have increased plasma concentrations of 44 2 inflammation related cytokines, including interleukins (IL) 2, 7, and 10, granulocyte-colony 45 stimulating factor (G-CSF), interferon--inducible protein 10 (IP10), monocyte 46 chemoattractant protein 1(MCP1), macrophage inflammatory protein 1 alpha (MIP1A), and 47 tumour necrosis factor  (TNF-), especially in moribund patients 10 . Importantly, 2019-nCoV 48 infected patients have developed characteristic pulmonary ground glass changes on imaging 49 and lymphocytes decreasing 11,12 . These phenomena suggest severe pulmonary inflammation 50 and cytokine storm also exist in 2019-nCoV infection. At present, symptomatic treatments 51 with organ support to moribund patients are the mainstays of clinical managements. It is 52 urgent to identify the immunopathology mechanism to delay the pulmonary immune injury. 53 54