Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals

IF 2.5 4区 医学 Q3 IMMUNOLOGY
Lizhong Zhang , Hongyi Li , Lei Shi , Jie Geng , Haojun Zhang , Haoran Chen , Peng Zhao , Yang Xiao , Jinqi Lu , Zhilun Li , Hongbin Pu , Chuandong Hou , Chenghui Li , Chumeng Gao , Xia Song , Zhuocheng Bao , Bing Zhai , Bo Guo , Bo Yang , Xuechun Lu , Qi Yu
{"title":"Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals","authors":"Lizhong Zhang ,&nbsp;Hongyi Li ,&nbsp;Lei Shi ,&nbsp;Jie Geng ,&nbsp;Haojun Zhang ,&nbsp;Haoran Chen ,&nbsp;Peng Zhao ,&nbsp;Yang Xiao ,&nbsp;Jinqi Lu ,&nbsp;Zhilun Li ,&nbsp;Hongbin Pu ,&nbsp;Chuandong Hou ,&nbsp;Chenghui Li ,&nbsp;Chumeng Gao ,&nbsp;Xia Song ,&nbsp;Zhuocheng Bao ,&nbsp;Bing Zhai ,&nbsp;Bo Guo ,&nbsp;Bo Yang ,&nbsp;Xuechun Lu ,&nbsp;Qi Yu","doi":"10.1016/j.imbio.2025.152898","DOIUrl":null,"url":null,"abstract":"<div><div>During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (−15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152898"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171298525000324","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (−15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.
依那西普治疗老年人冠状病毒病2019自身免疫样表现的机制及疗效
在2019冠状病毒病大流行期间,广泛的研究侧重于普遍治疗,但很少有研究涉及老年患者的治疗方案。本研究旨在评估依那西普(一种TNF抑制剂)对老年COVID-19患者的影响,通过对富有同情心的用例进行观察分析。结果显示,依那西普治疗1个月后,c反应蛋白、d -二聚体、纤维蛋白原等临床指标恢复正常,而接受常规治疗的对照组未完全恢复。对7名接受依那西普治疗的患者和2名未感染的个体进行单细胞测序。基于我们的数据并结合外部数据,创建了一个包含40万个细胞的综合特征图。转录组学分析揭示了老年患者的自身免疫样表现,强调了免疫治疗的重要性。浆细胞、血小板和B细胞是治疗最敏感的细胞。对包括抗病毒、依那西普、糖皮质激素、托珠单抗等在内的五种药物类型的分析显示,托珠单抗与老年患者血栓形成风险增加有关。依那西普通过抑制血小板因子4和TNF-α减轻自身免疫样表现。分子对接显示依那西普对SARS-CoV-2 Omicron变体的刺突蛋白具有很强的亲和力(- 15.0 kcal/mol),提示其可能对免疫功能低下的患者有保护作用。我们的研究结果支持依那西普作为具有自身免疫样表现的老年COVID-19患者的潜在治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信