Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort

Immunity response following vaccination and infection toward the SARS-CoV-2 Omicron variant remains limited in chronic liver disease (CLD) population. This study aims to investigate humoral and cell-mediate immunity to Omicron BA.4/5 among CLD patients with/without breakthrough infections (BI). This...

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Main Authors: Yongmei Liu, Yuzhu Shi, Haoting Zhan, Yuling Wang, Wenfang Yuan, Yuchen Xie, Linlin Cheng, Xinru Guo, Xiaomeng Li, Haiyan Kang, Haolong Li, Yongliang Chen, Xingli Sun, Huixia Gao, Fumin Feng, Erhei Dai, Yongzhe Li
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2025.2544466
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author Yongmei Liu
Yuzhu Shi
Haoting Zhan
Yuling Wang
Wenfang Yuan
Yuchen Xie
Linlin Cheng
Xinru Guo
Xiaomeng Li
Haiyan Kang
Haolong Li
Yongliang Chen
Xingli Sun
Huixia Gao
Fumin Feng
Erhei Dai
Yongzhe Li
author_facet Yongmei Liu
Yuzhu Shi
Haoting Zhan
Yuling Wang
Wenfang Yuan
Yuchen Xie
Linlin Cheng
Xinru Guo
Xiaomeng Li
Haiyan Kang
Haolong Li
Yongliang Chen
Xingli Sun
Huixia Gao
Fumin Feng
Erhei Dai
Yongzhe Li
author_sort Yongmei Liu
collection DOAJ
description Immunity response following vaccination and infection toward the SARS-CoV-2 Omicron variant remains limited in chronic liver disease (CLD) population. This study aims to investigate humoral and cell-mediate immunity to Omicron BA.4/5 among CLD patients with/without breakthrough infections (BI). This longitudinal study characterized immune responses to Omicron infection across three CLD patient groups: vaccinated without BI (group 1, n = 10), vaccinated with BI (group 2, n = 43), and unvaccinated infected (group 3, n = 7). SARS-CoV-2-specific antibodies/T-cell responses and lymphocyte phenotypes were quantified by ELISA and flow cytometry. Logistic regression identified immunological correlates of BI event, viral clearance and liver disease progression. Dynamic immunity changes after infection analyzed using Spearman’s correlation. Patients in group 2 exhibited the highest levels of neutralizing antibodies (NAbs) against wildtype (WT) and Omicron BA.4.5, anti-RBD IgG, and total anti-SARS-CoV-2 antibodies compared to groups 1 and 3. Comparable T cell responses were observed between two vaccinated groups, stronger than unvaccinated individuals. Hybrid immune (vaccination plus infection) elicited stronger NAbs-WT, total anti-SARS-CoV-2 antibodies, anti-RBD IgG, MBCs, and Omicron-specific IFN-γ+/IL-4+CD4+T cells compared to primary Omicron infection. Besides, severe liver disease was not only a risk factor for BI, but also impaired Omicron-specific IFN-γ+CD8+T, CD38+CD4+T, and CD45RA+CD8+T cells responses after infection. Importantly, IgG+/IgM+MBCs and NAbs showed positive associations with central memory (CD45RA−CD62L+CD4/8) or naive (CD45RA+CD62L+CD4) T cells. Low levels of CD45RA+CD62L+CD8+T cells and resting MBCs were identified as the independent risk factors for viral clearance and disease progression, respectively. BI predominantly stimulates humoral immunity without enhancing cellular responses. Weaker immune response induced by primary Omicron infection underscores the need for additional vaccinations in vaccine-naïve CLD patients. The positive correlations between humoral/cellular immunity and memory/activated T cells reveal their coordinated role in adaptive immune defense against SARS-CoV-2. These findings emphasize the importance of regular immune monitoring and timely interventions to optimize protection for CLD patients against emerging Omicron subvariants.
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spelling doaj-art-e42f059e2d8a4df0ad2ee8c30aef10682025-08-20T03:41:44ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2025-12-0121110.1080/21645515.2025.2544466Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohortYongmei Liu0Yuzhu Shi1Haoting Zhan2Yuling Wang3Wenfang Yuan4Yuchen Xie5Linlin Cheng6Xinru Guo7Xiaomeng Li8Haiyan Kang9Haolong Li10Yongliang Chen11Xingli Sun12Huixia Gao13Fumin Feng14Erhei Dai15Yongzhe Li16Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Public Health, North China University of Science and Technology, Tangshan, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaSchool of Public Health, North China University of Science and Technology, Tangshan, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Public Health, North China University of Science and Technology, Tangshan, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaSchool of Public Health, North China University of Science and Technology, Tangshan, ChinaHebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaImmunity response following vaccination and infection toward the SARS-CoV-2 Omicron variant remains limited in chronic liver disease (CLD) population. This study aims to investigate humoral and cell-mediate immunity to Omicron BA.4/5 among CLD patients with/without breakthrough infections (BI). This longitudinal study characterized immune responses to Omicron infection across three CLD patient groups: vaccinated without BI (group 1, n = 10), vaccinated with BI (group 2, n = 43), and unvaccinated infected (group 3, n = 7). SARS-CoV-2-specific antibodies/T-cell responses and lymphocyte phenotypes were quantified by ELISA and flow cytometry. Logistic regression identified immunological correlates of BI event, viral clearance and liver disease progression. Dynamic immunity changes after infection analyzed using Spearman’s correlation. Patients in group 2 exhibited the highest levels of neutralizing antibodies (NAbs) against wildtype (WT) and Omicron BA.4.5, anti-RBD IgG, and total anti-SARS-CoV-2 antibodies compared to groups 1 and 3. Comparable T cell responses were observed between two vaccinated groups, stronger than unvaccinated individuals. Hybrid immune (vaccination plus infection) elicited stronger NAbs-WT, total anti-SARS-CoV-2 antibodies, anti-RBD IgG, MBCs, and Omicron-specific IFN-γ+/IL-4+CD4+T cells compared to primary Omicron infection. Besides, severe liver disease was not only a risk factor for BI, but also impaired Omicron-specific IFN-γ+CD8+T, CD38+CD4+T, and CD45RA+CD8+T cells responses after infection. Importantly, IgG+/IgM+MBCs and NAbs showed positive associations with central memory (CD45RA−CD62L+CD4/8) or naive (CD45RA+CD62L+CD4) T cells. Low levels of CD45RA+CD62L+CD8+T cells and resting MBCs were identified as the independent risk factors for viral clearance and disease progression, respectively. BI predominantly stimulates humoral immunity without enhancing cellular responses. Weaker immune response induced by primary Omicron infection underscores the need for additional vaccinations in vaccine-naïve CLD patients. The positive correlations between humoral/cellular immunity and memory/activated T cells reveal their coordinated role in adaptive immune defense against SARS-CoV-2. These findings emphasize the importance of regular immune monitoring and timely interventions to optimize protection for CLD patients against emerging Omicron subvariants.https://www.tandfonline.com/doi/10.1080/21645515.2025.2544466Hybrid immunityimmunogenicitydisease severityviral clearanceprognosis
spellingShingle Yongmei Liu
Yuzhu Shi
Haoting Zhan
Yuling Wang
Wenfang Yuan
Yuchen Xie
Linlin Cheng
Xinru Guo
Xiaomeng Li
Haiyan Kang
Haolong Li
Yongliang Chen
Xingli Sun
Huixia Gao
Fumin Feng
Erhei Dai
Yongzhe Li
Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
Human Vaccines & Immunotherapeutics
Hybrid immunity
immunogenicity
disease severity
viral clearance
prognosis
title Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
title_full Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
title_fullStr Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
title_full_unstemmed Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
title_short Distinct features of humoral and cellular immunity against Omicron breakthrough infection among chronic liver disease patients: An experience from a follow-up cohort
title_sort distinct features of humoral and cellular immunity against omicron breakthrough infection among chronic liver disease patients an experience from a follow up cohort
topic Hybrid immunity
immunogenicity
disease severity
viral clearance
prognosis
url https://www.tandfonline.com/doi/10.1080/21645515.2025.2544466
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