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新冠病毒感染中炎症增强、适应性免疫抑制且病毒RNA持续脱落

Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding.

作者信息

Tang Xiaohua, Sun Rui, Ge Weigang, Mao Tingting, Qian Liujia, Huang Chongquan, Kang Zhouyang, Xiao Qi, Luo Meng, Zhang Qiushi, Li Sainan, Chen Hao, Liu Wei, Wang Bingjie, Li Shufei, Lin Xiaoling, Xu Xueqin, Li Huanzheng, Wu Lianpeng, Dai Jianyi, Gao Huanhuan, Li Lu, Lu Tian, Liang Xiao, Cai Xue, Ruan Guan, Xu Fei, Li Yan, Zhu Yi, Kong Ziqing, Huang Jianping, Guo Tiannan

机构信息

Wenzhou Central Hospital, Dingli Clinical Medical School of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Genetics and genomic medicine, Zhejiang Provincial people's hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.

出版信息

Cell Discov. 2022 Jul 25;8(1):70. doi: 10.1038/s41421-022-00441-y.

DOI:10.1038/s41421-022-00441-y
PMID:35879274
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9311354/
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.

摘要

关于为什么一部分新冠病毒疾病（COVID-19）患者的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染呈现出阳性持续时间延长，目前所知甚少。在此，我们发现，就病毒载量而言，与病毒RNA病程短（SC）的患者相比，病毒RNA病程长（LC）的患者表现出高水平IgG抗体持续时间延长以及调节性T（Treg）细胞计数更高。对患者血清进行的纵向蛋白质组学和代谢组学分析发现，病毒RNA持续脱落与肝脏X受体/视黄酸X受体（LXR/RXR）途径的抑制、多种代谢物的显著抑制、补体系统激活、细胞迁移受抑制以及病毒复制增强有关。此外，还建立了一个十分子学习模型，该模型有可能预测病毒RNA脱落期。总之，本研究揭示了病毒RNA持续脱落的COVID-19患者炎症增强且适应性免疫受抑制，并提出了一种用于预测病毒RNA脱落的多组学分类器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/ca4ab9c54212/41421_2022_441_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/ca4ab9c54212/41421_2022_441_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/4db5c369cb9b/41421_2022_441_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/a8da2b3bdb27/41421_2022_441_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/979b5641b379/41421_2022_441_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6572/9314413/afaf0ce60a58/41421_2022_441_Fig4_HTML.jpg
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