Evidence map›Paper›PMID 42106820›Full record

ArticleRespiratory research2026

Compartment-specific phase compensation between pulmonary T-Cell immunity and waning systemic responses in BA.5 breakthrough infection.

Peiyu Huang, Xinyue Mei, Hao Xu, Qi Wan, Xiaohui Wu, Jieqi Peng, Kunning Zhou, Gang Yang, Li Cheng, Shijun Bu and 13 more

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Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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23 authors.

Peiyu Huang *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Xinyue Mei *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Hao Xu *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Qi WanState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Xiaohui WuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Jieqi PengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Kunning ZhouState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Gang YangDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan province, Kunming, Yunnan, China.
Li ChengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Shijun BuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Zhishan DengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Fan WuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Cuiqiong DaiState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Daxiang ChenState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Qi LuoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Xi SunState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Jie SuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Shidong DengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Siying WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Yufen LiuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
Pixin RanState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. pxran@gzhmu.edu.cn.
Zhongfang WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. wangzhongfang@gird.cn.
Yumin ZhouState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. zhouyumin410@126.com.

Funding

Clinical and Epidemiological Research Project of State Key Laboratory of Respiratory Disease SKLRD-L-202402Emergency Key Program of Guangzhou Laboratory No. EKPG21-30-1Foundation of Guangzhou National Laboratory SRPG22-016Foundation of Guangzhou National Laboratory SRPG22-018Foundation of Guangzhou National Laboratory SRPG23-005National Key Research and Development Program of China 2023YFC2306400National Natural Science Foundation of China 81970045Plan on Enhancing Scientific Research in Guangzhou Medical University No. GMUCR2024-01012
6 · The paper itself

Abstract

backgroundSpatiotemporal coordination of SARS-CoV-2-specific immunity across pulmonary and systemic compartments is poorly defined, especially how chronic lung diseases modulate this. We hypothesized that profiling virus-specific T cells (VSTs) and antibodies in respiratory vs. blood samples would reveal compartmentalized dynamics critical for viral control.

methodsIn 64 mild Omicron BA.5 breakthrough-infected participants (30 early [D7], 34 later [D14]), we performed: 1) Paired sputum/PBMCs flow cytometry for CD4⁺/CD8⁺ VSTs; 2) Systemic antibody titration (NAbs, anti-N IgG); 3) Compartmental cytokine profiling; 4) Stratified analysis of GOLD I-II COPD (n = 28) vs controls (n = 36).

resultsPulmonary CD4⁺ VSTs increased 2.8-fold from D7 to D14, contrasting with delayed CD8⁺ VSTs mobilisation, while no sputum-blood VSTs correlations existed in either phase (all P > 0.05). Phase-dependent immune synergy was observed in that early viral control was driven by blood CD8⁺ VSTs-NAbs coordination (CT value: r = 0.43; NAbs: r = 0.41; both P < 0.05), whereas later-phase pulmonary CD4⁺ VSTs expanded reciprocally to waning systemic antibodies (NAbs: r = -0.54, P < 0.01), indicating local compensation. Pulmonary cytokine dominance was evident as sputum IL-1β/IL-6/RANTES inversely correlated with viral titer (CT value) at D7 (all P < 0.05), exhibiting stronger virological associations than their plasma counterparts. Additionally, GOLD I-II COPD patients showed no impairment in viral clearance, NAbs titres, or VSTs magnitudes versus controls (all P > 0.05).

conclusionsNon-invasive sputum analysis reveals dynamic SARS-CoV-2 immunity: systemic effectors dominate early control, while pulmonary CD4⁺ VSTs compensate during antibody decline, underscoring the need for phase-specific therapeutic regimens targeting distinct compartments.

Indexed as

CD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCOVID-19Immunity, CellularLungSARS-CoV-2AgedAntibodies, ViralBreakthrough InfectionsCytokinesFemaleHumansMaleMiddle AgedPulmonary Disease, Chronic ObstructiveSputumAntibodies, ViralCytokinesCompartmentalized immunityCOPDSARS-CoV-2Sputum-based detectionVirus-specific T cells

Identifiers

PMID42106820
PMCPMC13330283

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.