Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.

Chen, Yan-Mei; Zheng, Yuanting; Yu, Ying; Wang, Yunzhi; Huang, Qingxia; Qian, Feng; Sun, Lei; Song, Zhi-Gang; Chen, Ziyin; Feng, Jinwen; An, Yanpeng; Yang, Jingcheng; Su, Zhenqiang; Sun, Shanyue; Dai, Fahui; Chen, Qinsheng; Lu, Qinwei; Li, Pengcheng; Ling, Yun; Yang, Zhong; Tang, Huiru; Shi, Leming; Jin, Li; Holmes, Edward C; Ding, Chen; Zhu, Tong-Yu; Zhang, Yong-Zhen

COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19 patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signalling as well as a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19 patients experiencing milder disease symptoms showed robust T cell responses. Finally, we identified genes, proteins and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.