Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months

ObjectivesTo evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.MethodThe neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets’ responses were tested through intracellular cytokine staining an...

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Main Authors: Qin Luo, Qinqin Song, Yan Li, Kexin Zong, Ti Liu, Junming He, Guoyong Mei, Haijun Du, Zhiqiang Xia, Mi Liu, Juan Song, Chen Gao, Dong Xia, Guangyu Xue, Wenyan Tian, Yinli Qu, Zengqiang Kou, Zhongjun Dong, Jun Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1596065/full
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author Qin Luo
Qinqin Song
Yan Li
Kexin Zong
Ti Liu
Junming He
Guoyong Mei
Haijun Du
Zhiqiang Xia
Mi Liu
Juan Song
Chen Gao
Dong Xia
Guangyu Xue
Wenyan Tian
Yinli Qu
Zengqiang Kou
Zhongjun Dong
Zhongjun Dong
Jun Han
author_facet Qin Luo
Qinqin Song
Yan Li
Kexin Zong
Ti Liu
Junming He
Guoyong Mei
Haijun Du
Zhiqiang Xia
Mi Liu
Juan Song
Chen Gao
Dong Xia
Guangyu Xue
Wenyan Tian
Yinli Qu
Zengqiang Kou
Zhongjun Dong
Zhongjun Dong
Jun Han
author_sort Qin Luo
collection DOAJ
description ObjectivesTo evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.MethodThe neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets’ responses were tested through intracellular cytokine staining and flow cytometry.ResultsThe neutralizing antibodies titers against WT and BA.5 strain, remaining high level for at least 6 months, were higher than that of both XBB.1 and EG.5 variants. The neutralizing antibodies of WT, BA.5, XBB.1, and EG.5 strains in the elderly were slightly lower than those in middle-age. The memory B cells decreased rapidly in the elderly, and Tfh, Th17 cells of the elderly continued to increase for only 3 months, while Tfh and Th17 cells increased in the middle-aged for over 6 months. For the elderly, after peptide stimulation, unswitched/switched memory B cells decreased, while double negative B cells displayed higher proliferation. The proportions of both naïve and Temra cells in CD4+ and CD8+ T cells declined, whereas those of Tcm and Tem cells elevated. In the meantime, both CD69+ and CD38+ T cells decreased, but the frequencies of PD-1+ and CTLA-4+ of CD4+ and CD8+ T cells showed an increasing trend. The proportions of PD-1+ and CTLA-4+ cells also increased in older people with long COVID symptoms at 3m post-infection.ConclusionsOmicron BA.5 infection induced lower neutralizing antibodies against XBB.1 and EG.5 variant. The decrease of memory B cells, CD69+ and CD38+T cells, as well as the increase of PD-1+, CTLA-4+ of CD4+/CD8+T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.
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spelling doaj-art-e91deb1b1d3048a88e6cd9b53c997ccd2025-08-20T02:16:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15960651596065Reduced immune response to SARS-CoV-2 infection in the elderly after 6 monthsQin Luo0Qinqin Song1Yan Li2Kexin Zong3Ti Liu4Junming He5Guoyong Mei6Haijun Du7Zhiqiang Xia8Mi Liu9Juan Song10Chen Gao11Dong Xia12Guangyu Xue13Wenyan Tian14Yinli Qu15Zengqiang Kou16Zhongjun Dong17Zhongjun Dong18Jun Han19National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaShandong Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Intelligent Monitoring, Early Warning, and Prevention and Control of Infectious Diseases, Shandong Institute of Preventive Medicine, Jinan, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaShandong Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Intelligent Monitoring, Early Warning, and Prevention and Control of Infectious Diseases, Shandong Institute of Preventive Medicine, Jinan, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaShandong Center for Disease Control and Prevention, Shandong Provincial Key Laboratory of Intelligent Monitoring, Early Warning, and Prevention and Control of Infectious Diseases, Shandong Institute of Preventive Medicine, Jinan, ChinaThe First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei, ChinaState Key Laboratory of Membrane Biology, School of Medicine and Institute for Immunology, Tsinghua University, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaObjectivesTo evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.MethodThe neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets’ responses were tested through intracellular cytokine staining and flow cytometry.ResultsThe neutralizing antibodies titers against WT and BA.5 strain, remaining high level for at least 6 months, were higher than that of both XBB.1 and EG.5 variants. The neutralizing antibodies of WT, BA.5, XBB.1, and EG.5 strains in the elderly were slightly lower than those in middle-age. The memory B cells decreased rapidly in the elderly, and Tfh, Th17 cells of the elderly continued to increase for only 3 months, while Tfh and Th17 cells increased in the middle-aged for over 6 months. For the elderly, after peptide stimulation, unswitched/switched memory B cells decreased, while double negative B cells displayed higher proliferation. The proportions of both naïve and Temra cells in CD4+ and CD8+ T cells declined, whereas those of Tcm and Tem cells elevated. In the meantime, both CD69+ and CD38+ T cells decreased, but the frequencies of PD-1+ and CTLA-4+ of CD4+ and CD8+ T cells showed an increasing trend. The proportions of PD-1+ and CTLA-4+ cells also increased in older people with long COVID symptoms at 3m post-infection.ConclusionsOmicron BA.5 infection induced lower neutralizing antibodies against XBB.1 and EG.5 variant. The decrease of memory B cells, CD69+ and CD38+T cells, as well as the increase of PD-1+, CTLA-4+ of CD4+/CD8+T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1596065/fullomicron BA.5elderlyneutralizing antibodyadaptive immunityT cell
spellingShingle Qin Luo
Qinqin Song
Yan Li
Kexin Zong
Ti Liu
Junming He
Guoyong Mei
Haijun Du
Zhiqiang Xia
Mi Liu
Juan Song
Chen Gao
Dong Xia
Guangyu Xue
Wenyan Tian
Yinli Qu
Zengqiang Kou
Zhongjun Dong
Zhongjun Dong
Jun Han
Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
Frontiers in Immunology
omicron BA.5
elderly
neutralizing antibody
adaptive immunity
T cell
title Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
title_full Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
title_fullStr Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
title_full_unstemmed Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
title_short Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months
title_sort reduced immune response to sars cov 2 infection in the elderly after 6 months
topic omicron BA.5
elderly
neutralizing antibody
adaptive immunity
T cell
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1596065/full
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