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Proteomics Uncovers Immunosuppression in COVID-19 Patients with Long Disease Course

By Shaohua Tang, Rui Sun, Qi Xiao, Tingting Mao, Weigang Ge, Chongquan Huang, Meng Luo, Liujia Qian, Hao Chen, Qiushi Zhang, Sainan Li, Wei Liu, Shufen Li, Xueqin Xu, Huangzheng Li, Lianpeng Wu, Jianyi Dai, Huanhuan Gao, Lu Li, Tian Lu, Xiao Liang, Xue Cai, Guan Ruan, Kexin Liu, Fei Xu, Yan Li, Yi Zhu, Jianping Huang, Tiannan Guo

Posted 16 Jun 2020
medRxiv DOI: 10.1101/2020.06.14.20131078

Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we present a longitudinal sera proteomic resource for 37 COVID-19 patients over nine weeks, in which 2700 proteins were quantified with high quality. Remarkably, we found that during the first three weeks since disease onset, while clinical symptoms and outcome were indistinguishable, patients with prolonged disease course displayed characteristic immunological responses including enhanced Natural Killer (NK) cell-mediated innate immunity and regulatory T cell-mediated immunosuppression. We further showed that it is possible to predict the length of disease course using machine learning based on blood protein levels during the first three weeks. Validation in an independent cohort achieved an accuracy of 82%. In summary, this study presents a rich serum proteomic resource to understand host responses in COVID-19 patients and identifies characteristic Treg-mediated immunosuppression in LC patients, nominating new therapeutic target and diagnosis strategy.

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