Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Lulin Huang; Yi Shi; Bo Gong; Li Jiang; Xiaoqi Liu; Jialiang Yang; Juan Tang; Chunfang You; Qi Jiang; Bo Long; Tao Zeng; Mei Luo; Fanwei Zeng; Fanxin Zeng; Shuqiang Wang; Xingxiang Yang; Zhenglin Yang

The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03. 15.20033472 doi: medRxiv preprint In summary, we demonstrated that SARS-CoV-2 can enter the blood through the circulatory system and cause a blood immune response after infection through the respiratory system. Therefore, in patients with COVID-19, the damage is related to multiple organs (32) . The leukocyte immune responses involve many cell subtypes, including CD8+ T cells, CD8 cytotoxic T cells, CD4+ T cells, CD4+ cytotoxic T cells, CD1C+_B dendritic cells and other cell subtypes. After the virus reaches the blood immune cells, it might replicate-mainly in AXL+SIGLEC6+ dendritic cells, CD4+ T cells, and naive CD8+ T cells and might activate multiple cell subtypes of the interferon signal pathway to produce effectors, such as IFI27, IFITM1 and IFITM3, to fight the SARS-CoV-2 virus. The similar process also happened to Influenza and West Nile Virus infection in human (23, 24) . Through downstream activation of MAPK, the expression of downstream effectors is activated by key transcription factors, such as FOS, JUN, and JUNB, which lead to a wide range of antiviral responses in the blood system (Fig. 4C) . These results suggested that the immune response may come back the normal situation when the patients recovery, and the MAPK signal is thus inhibited.