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

Among these pathways, the most important was over-activation of the interferonrelated signaling pathways, including 2'-5'-oligoadenylate synthase and type I interferon signaling pathway(naive CD8+ T cells, CD4+ T cells, and other cells) and interferon alpha/beta/gamma signaling (naive CD8+ T cells, CD4+ T cells, and other cells) (Fig. 2C , Table S3 ). In other COVID-19 conditions, the interferon signal was also over-activated to varying degrees. However, in the cured patients, the interferon signal was just mildly activated compared to the patients with severe and moderate conditions. In the cured condition, the signal pathway related to mRNA translation of the virus was suppressed, while the signal pathway related to MAPK was significantly enriched (Fig. 2C , Table S3-6). To detect whether these signaling pathway changes were specific to COVID-19, we compared the COVID-19 patients with the patients with influenza A (patient 11), acute pharyngitis (patient 12), and cerebral infarction (patient 13) and found that the signaling pathways were still enriched after filtering with these related disease controls (Fig. S14 ). Among these pathways, the interferon-MAPK signaling pathway was the major blood immune response for COVID-19 infection. 7 7 The activation of the MAPK signaling pathway by interferon involves a set of defense mechanisms evolved by human beings to fight against viral infections (19) (20) (21) .