Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19

Tan, Yun; Zhang, Wei; Zhu, Zhaoqin; Qiao, Niu; Ling, Yun; Guo, Mingquan; Yin, Tong; Fang, Hai; Xu, Xiaoguang; Lu, Gang; Zhang, Peipei; Yang, Shuangshuang; Fu, Ziyu; Liang, Dongguo; Xie, Yinyin; Zhang, Ruihong; Jiang, Lu; Yu, Shuting; Lu, Jing; Jiang, Fangying; Chen, Jian; Xiao, Chenlu; Wang, Shengyue; Chen, Shuo; Bian, Xiu-Wu; Lu, Hongzhou; Liu, Feng; Chen, Saijuan

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.