Cell Discovery (Jul 2022)
Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding
- Xiaohua Tang,
- Rui Sun,
- Weigang Ge,
- Tingting Mao,
- Liujia Qian,
- Chongquan Huang,
- Zhouyang Kang,
- Qi Xiao,
- Meng Luo,
- Qiushi Zhang,
- Sainan Li,
- Hao Chen,
- Wei Liu,
- Bingjie Wang,
- Shufei Li,
- Xiaoling Lin,
- Xueqin Xu,
- Huanzheng Li,
- Lianpeng Wu,
- Jianyi Dai,
- Huanhuan Gao,
- Lu Li,
- Tian Lu,
- Xiao Liang,
- Xue Cai,
- Guan Ruan,
- Fei Xu,
- Yan Li,
- Yi Zhu,
- Ziqing Kong,
- Jianping Huang,
- Tiannan Guo
Affiliations
- Xiaohua Tang
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Rui Sun
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Weigang Ge
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Tingting Mao
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Liujia Qian
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Chongquan Huang
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Zhouyang Kang
- Zhejiang University School of Medicine
- Qi Xiao
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Meng Luo
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Qiushi Zhang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Sainan Li
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Hao Chen
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Wei Liu
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Bingjie Wang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Shufei Li
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Xiaoling Lin
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Xueqin Xu
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Huanzheng Li
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Lianpeng Wu
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Jianyi Dai
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Huanhuan Gao
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Lu Li
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Tian Lu
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Xiao Liang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Xue Cai
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Guan Ruan
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Fei Xu
- Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University
- Yan Li
- Department of Anatomy and Physiology, College of Basic Medical Sciences, Shanghai Jiao Tong University
- Yi Zhu
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- Ziqing Kong
- Calibra Lab in DIAN Diagnostics, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province
- Jianping Huang
- Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University
- Tiannan Guo
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine
- DOI
- https://doi.org/10.1038/s41421-022-00441-y
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 18
Abstract
Abstract Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.
