Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals
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 compass...
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Elsevier
2025-05-01
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| Series: | Immunobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298525000324 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lizhong Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7291469cead84d189a7f6fa98458d409 |
| institution | OA Journals |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immunobiology |
| spelling | doaj-art-7291469cead84d189a7f6fa98458d4092025-08-20T02:03:14ZengElsevierImmunobiology0171-29852025-05-01230315289810.1016/j.imbio.2025.152898Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individualsLizhong Zhang0Hongyi Li1Lei Shi2Jie Geng3Haojun Zhang4Haoran Chen5Peng Zhao6Yang Xiao7Jinqi Lu8Zhilun Li9Hongbin Pu10Chuandong Hou11Chenghui Li12Chumeng Gao13Xia Song14Zhuocheng Bao15Bing Zhai16Bo Guo17Bo Yang18Xuechun Lu19Qi Yu20Basic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Medical School of Chinese PLA, Beijing 100853, ChinaSenior Department of Infectious Diseases, the Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, 100853, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaSchool of Management, Shanxi Medical University, Taiyuan, 030000, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Medical School of Chinese PLA, Beijing 100853, ChinaDepartment of Computer Science, Whiting School of Engineering, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USASchool of basic medicine and clinical pharmacy, China Pharmaceutical University, Nanjing 211100, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Medical School of Chinese PLA, Beijing 100853, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Medical School of Chinese PLA, Beijing 100853, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Medical School of Chinese PLA, Beijing 100853, ChinaFuxing Road Outpatient Department, Jingnan Medical District, PLA General Hospital, Beijing 100842, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, ChinaDepartment of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, ChinaBasic Medicine College, Shanxi Medical University, Taiyuan 030000, China; Department of Hematology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing 100853, China; Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China; Corresponding author.Basic Medicine College, Shanxi Medical University, Taiyuan 030000, China; School of Management, Shanxi Medical University, Taiyuan, 030000, China; Shanxi Key Laboratory of Big Data for Clinical Decision, Shanxi Medical University, Taiyuan, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0171298525000324Long COVIDSARS-CoV-2Single-cell RNA-SeqPlatelet factor 4Etanercept |
| spellingShingle | 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 Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals Immunobiology Long COVID SARS-CoV-2 Single-cell RNA-Seq Platelet factor 4 Etanercept |
| title | Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals |
| title_full | Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals |
| title_fullStr | Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals |
| title_full_unstemmed | Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals |
| title_short | Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals |
| title_sort | mechanism and efficacy of etanercept in treating autoimmune like manifestations of coronavirus disease 2019 in elderly individuals |
| topic | Long COVID SARS-CoV-2 Single-cell RNA-Seq Platelet factor 4 Etanercept |
| url | http://www.sciencedirect.com/science/article/pii/S0171298525000324 |
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