{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:34:09Z","timestamp":1792020849075,"version":"4.4.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elderly patients with chronic obstructive pulmonary disease (COPD) are at increased risk of severe coronavirus disease 2019 (COVID-19) outcomes. We aimed to assess the safety and longitudinal antibody dynamics of a three-dose schedule of the inactivated COVID-19 vaccine (Vero cell, Covilo) in elderly patients with COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective cohort study enrolled 410 COPD patients (aged\u226560), 80 younger healthy controls (HCs, 18\u201359 years), and 108 older HCs (\u226560 years) in Zhejiang Province, China. COPD patients received a three-dose regimen (Day 0, 21, and 111), while HCs received a standard two-dose series. Neutralizing antibodies (NAbs), anti-receptor-binding domain IgG (anti-RBD IgG), and anti-spike &amp;amp; nucleocapsid IgG (anti-S&amp;amp;N IgG) were measured at five time points to evaluate the immunogenicity. Safety was assessed within 7 days after each dose and throughout follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall incidence of adverse events in COPD patients was 10.24%, predominantly mild (Grade 1), with decreasing frequency across doses. After the two-dose primary series, NAbs seroconversion rates at 28\u201335 days were comparable between COPD patients (60.19%) and HCs (63.64%\u201366.67%). However, antibody concentration declined markedly within three months, particularly for NAbs. Strong positive correlations were observed among NAbs, anti-RBD IgG, and anti-S&amp;amp;N IgG (Spearman\u2019s \u03c1 = 0.754\u20130.905; p&amp;lt; 0.001). A third dose administered after approximately three months significantly increased NAbs seroconversion rate to 83.50% and markedly elevated antibody concentrations to 207.22 U\/mL. Despite the booster, NAbs declined significantly six months after the third dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A three-dose regimen of Covilo is safe and effectively elicits antibody responses in elderly COPD patients. However, the rapid waning of antibody levels suggests a need for optimized booster strategies to maintain long-term protection in this vulnerable group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1840305","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:47:30Z","timestamp":1781156850000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and antibody responses to inactivated COVID-19 vaccines among elderly patients with COPD: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Immunization Program, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Yuyao Municipal Center for Disease Control and Prevention","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinjing","family":"Sun","sequence":"additional","affiliation":[{"name":"Haining Municipal Center for Disease Control and Prevention","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hexiang","family":"Jia","sequence":"additional","affiliation":[{"name":"Xiaoshan District Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Shu","sequence":"additional","affiliation":[{"name":"Jiande Municipal Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheren","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiande Municipal Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prevention and Control of Infectious Disease, Key Lab of Vaccine, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]},{"name":"School of Public Health, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunization Program, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","unstructured":"WHO Coronavirus (COVID-19) Dashboard\n          \n          \n          \n          2026"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1900164","DOI":"10.1183\/13993003.00164-2019","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019","volume":"53","author":"Singh","year":"2019","journal-title":"Eur Respir J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100789","article-title":"COPD and the risk of poor outcomes in COVID-19: A systematic review and meta-analysis","volume":"33","author":"Gerayeli","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1556\/2060.2022.00172","article-title":"COVID-19 infection in patients with chronic obstructive pulmonary disease: From pathophysiology to therapy. Mini-review","volume":"109","author":"Fekete","year":"2022","journal-title":"Physiol Int"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2024-002694","article-title":"COVID-19 and risk of long-term mortality in COPD: a nationwide population-based cohort study","volume":"12","author":"Lee","year":"2025","journal-title":"BMJ Open Respir Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.32751","article-title":"Evaluation of the effect of COVID-19 vaccination on exacerbations of chronic obstructive pulmonary disease: A single-center study","volume":"14","author":"Sahin Ozdemirel","year":"2022","journal-title":"Cureus"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.02.008","article-title":"Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis","volume":"41","author":"Watanabe","year":"2023","journal-title":"Vaccine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.2147\/copd.S394101","article-title":"Efficacy of mRNA and inactivated whole virus vaccines against COVID-19 in patients with chronic respiratory diseases","volume":"18","author":"Kwok","year":"2023","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11081392","article-title":"COPD-related mortality before and after mass COVID-19 vaccination in Northern Italy","volume":"11","author":"Fedeli","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2147\/copd.S340730","article-title":"The current status of vaccine uptake and the impact of COVID-19 on intention to vaccination in patients with COPD in Beijing","volume":"16","author":"Song","year":"2021","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12040414","article-title":"The prevalence and determinants of hesitancy for regular COVID-19 vaccination among primary healthcare patients with asthma or COPD in Greece: A cross-sectional study","volume":"12","author":"Bouloukaki","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2023.2286686","article-title":"Awareness of and attitude toward COVID-19 vaccination among individuals with COPD and the strategies to overcome vaccine hesitation: A mini review","volume":"19","author":"Liang","year":"2023","journal-title":"Hum Vaccin Immunother"},{"key":"B13","unstructured":"Guidelines for the Technical Implementation of COVID-19 Vaccination\n          \n          \n          \n          2021"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(20)30843-4","article-title":"Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1\/2 clinical trial","volume":"21","author":"Zhang","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed7050081","article-title":"Characteristics of COVID-19 breakthrough infections among vaccinated individuals and associated risk factors: A systematic review","volume":"7","author":"Gopinath","year":"2022","journal-title":"Trop Med Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7104e4","article-title":"Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods - United States, December 2020-January 2022","volume":"71","author":"Iuliano","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.11.009","article-title":"Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis","volume":"114","author":"Zheng","year":"2022","journal-title":"Int J Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.114252","article-title":"Effectiveness of COVID-19 vaccine booster in the general population and in subjects with comorbidities. A population-based study in Spain","volume":"215","author":"Mallah","year":"2022","journal-title":"Environ Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1674-2397.2022.03.003","article-title":"Expert recommendations on booster immunization strategies of 2019-nCoV vaccines","volume":"15","author":"Song","year":"2022","journal-title":"Chin J Clin Infect Dis"},{"key":"B20","unstructured":"Guidelines for Adverse Event Classification Standards for Clinical Trials of Preventive Vaccines\n          \n          \n          \n          2019"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.84056","article-title":"Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China","volume":"12","author":"Zhang","year":"2023","journal-title":"Elife"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11101757","article-title":"Performance of a surrogate SARS-CoV-2-neutralizing antibody assay in natural infection and vaccination samples","volume":"11","author":"Chan","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.78766","article-title":"Immune responses to inactivated COVID-19 vaccine were decreased in Chinese patients with chronic respiratory diseases","volume":"20","author":"Yang","year":"2023","journal-title":"Int J Med Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-023-01364-7","article-title":"Effectiveness and respiratory adverse events following inactivated and mRNA COVID-19 vaccines in patients with COPD and asthma: A Chinese population-based study","volume":"47","author":"Qin","year":"2024","journal-title":"Drug Saf"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2147\/copd.S433269","article-title":"Airway and systemic immune responses following the third COVID-19 vaccination in COPD patients","volume":"18","author":"Southworth","year":"2023","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1186\/s12879-025-11254-1","article-title":"Safety comparison of mRNA, viral vector, and inactivated Covid-19 vaccines: incidence of adverse events following primary and booster doses among medical professionals in Malaysia","volume":"25","author":"Prabhu","year":"2025","journal-title":"BMC Infect Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00688-25","article-title":"Inadequate immune response to inactivated COVID-19 vaccine among older people living with HIV: a prospective cohort study","volume":"99","author":"Zhang","year":"2025","journal-title":"J Virol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28055","article-title":"Humoral responses after inactivated COVID-19 vaccination in individuals with and without prior SARS-CoV-2 infection: A prospective cohort study","volume":"94","author":"Jia","year":"2022","journal-title":"J Med Virol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28434","article-title":"Risk of waning humoral responses after inactivated or subunit recombinant SARS-CoV-2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China","volume":"95","author":"Li","year":"2023","journal-title":"J Med Virol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2022-001268","article-title":"Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases","volume":"9","author":"Harboe","year":"2022","journal-title":"BMJ Open Respir Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab447","article-title":"Persistence of the immune responses and cross-neutralizing activity with variants of concern following 2 doses of adjuvanted SCB-2019 coronavirus disease 2019 vaccine","volume":"224","author":"Richmond","year":"2021","journal-title":"J Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.940357","article-title":"Immunogenicity of COVID-19 vaccines in patients with diabetes mellitus: A systematic review","volume":"13","author":"Boroumand","year":"2022","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00400-2023","article-title":"Vaccine-elicited B- and T-cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients","volume":"9","author":"Liu","year":"2023","journal-title":"ERJ Open Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1038\/s43587-022-00292-y","article-title":"Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults","volume":"2","author":"Palacios-Pedrero","year":"2022","journal-title":"Nat Aging"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac199","article-title":"Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine but strong initial responses to a third dose","volume":"226","author":"Mwimanzi","year":"2022","journal-title":"J Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12979-023-00327-x","article-title":"Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults","volume":"20","author":"Semelka","year":"2023","journal-title":"Immun Ageing"},{"key":"B37","doi-asserted-by":"publisher","first-page":"126121","DOI":"10.1016\/j.vaccine.2024.07.022","article-title":"COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study","volume":"42","author":"Hoeve","year":"2024","journal-title":"Vaccine"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-066766","article-title":"SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study","volume":"12","author":"Ward","year":"2022","journal-title":"BMJ Open"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104446","article-title":"Effect of vaccine booster, vaccine type, and hybrid immunity on humoral and cellular immunity against SARS-CoV-2 ancestral strain and Omicron variant sublineages BA.2 and BA.5 among older adults with comorbidities: a cross sectional study","volume":"88","author":"Fong","year":"2023","journal-title":"EBioMedicine"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1455334","article-title":"Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults","volume":"15","author":"Kometani","year":"2024","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813728","article-title":"Humoral and cellular immune response elicited by the BNT162b2 COVID-19 vaccine booster in elderly","volume":"24","author":"Dalla Gasperina","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B42","unstructured":"COVID-19 advice for the public: Getting vaccinated\n          \n          \n          \n          2024"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1038\/s41467-022-30340-5","article-title":"Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant","volume":"13","author":"Zuo","year":"2022","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01677-z","article-title":"Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: a randomized phase 4 trial","volume":"28","author":"Li","year":"2022","journal-title":"Nat Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s2214-109x(22)00112-7","article-title":"Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine: a large-scale prospective cohort study","volume":"10","author":"Jara","year":"2022","journal-title":"Lancet Glob Health"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad090","article-title":"Real-world effectiveness of primary series and booster doses of inactivated coronavirus disease 2019 vaccine against Omicron BA.2 variant infection in China: A retrospective cohort study","volume":"228","author":"Tang","year":"2023","journal-title":"J Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)02717-3","article-title":"Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial","volume":"398","author":"Munro","year":"2021","journal-title":"Lancet"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2025.106576","article-title":"Heterologous COVID-19 vaccine schedule with protein-based prime (NVX-CoV2373) and mRNA boost (BNT162b2) induces strong humoral responses: Results from COV-BOOST trial","volume":"91","author":"Janani","year":"2025","journal-title":"J Infect"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1840305\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:47:32Z","timestamp":1781156852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1840305\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2026.1840305"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1840305","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"article-number":"1840305"}}