Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients
作者全名："Tang, Yingkui; Zhang, Peidong; Liu, Qiuyu; Cao, Luyang; Xu, Jingsong"
作者地址："[Tang, Yingkui; Zhang, Peidong; Xu, Jingsong] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Peoples R China; [Tang, Yingkui; Zhang, Peidong; Xu, Jingsong] Sichuan Univ, Canc Ctr, Chengdu, Peoples R China; [Liu, Qiuyu] Chongqing Med Univ, Yongchuan Hosp, Dept Crit Care Med, Chongqing, Peoples R China; [Cao, Luyang; Xu, Jingsong] Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou, Peoples R China"
通信作者："Xu, JS (通讯作者)，Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Peoples R China.; Xu, JS (通讯作者)，Sichuan Univ, Canc Ctr, Chengdu, Peoples R China.; Cao, LY; Xu, JS (通讯作者)，Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou, Peoples R China."
来源：FRONTIERS IN IMMUNOLOGY
关键词：COVID-19; pyroptosis; leukocytes; prognosis model; transcription factors
摘要："The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases."