PhenoAge acceleration predicts antibody persistence and breakthrough infection after SARS-CoV-2 vaccination and infection

Affiliations

¹ Division of Infectious Diseases, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Taiwan; College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan. Electronic address: woody1005@cgmh.org.tw.
² Intelligent Data Mining Laboratory, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Artificial Intelligence, Department of Digital Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, 145 Xingda St., South Dist., Taichung 402202, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. Electronic address: chialin@vghtc.gov.tw.
³ Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: yfchiu@mail.cgu.edu.tw.
⁴ Department of Health Care Management, College of Management, Chang Gung University, Taoyuan, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Electronic address: sherrychiu@mail.cgu.edu.tw.
⁵ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: ljw33db@cgmh.org.tw.
⁶ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: 8902014@cgmh.org.tw.
⁷ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: seanscwang@cgmh.org.tw.
⁸ Department of Physical Medicine and Rehabilitation, New Taipei Municipal, Tucheng Hospital, Chang Gung Memorial Hospital, New Taipei City 236, Taiwan; Department of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan; College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan. Electronic address: mr7171@cgmh.org.tw.
⁹ Division of Thoracic Medicine, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Chang Gung Medical Foundation, New Taipei City, Taiwan. Electronic address: shihow@cgmh.org.tw.
¹⁰ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Chang Gung Medical Foundation, New Taipei City 236, Taiwan. Electronic address: biology42@cgmh.org.tw.
¹¹ College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan City 33302, Taiwan. Electronic address: kuochenwei@cgmh.org.tw.
¹² College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan; Division of Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu 300193, Taiwan. Electronic address: d000014691@cgu.edu.tw.

PMID: 41076847
DOI: 10.1016/j.jiph.2025.102989

Free article

PhenoAge acceleration predicts antibody persistence and breakthrough infection after SARS-CoV-2 vaccination and infection

Jeng-How Yang et al. J Infect Public Health. 2025.

Free article

. 2025 Oct 10;18(12):102989.

doi: 10.1016/j.jiph.2025.102989. Online ahead of print.

Authors

Affiliations

¹ Division of Infectious Diseases, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Taiwan; College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan. Electronic address: woody1005@cgmh.org.tw.
² Intelligent Data Mining Laboratory, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Artificial Intelligence, Department of Digital Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, 145 Xingda St., South Dist., Taichung 402202, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. Electronic address: chialin@vghtc.gov.tw.
³ Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: yfchiu@mail.cgu.edu.tw.
⁴ Department of Health Care Management, College of Management, Chang Gung University, Taoyuan, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Electronic address: sherrychiu@mail.cgu.edu.tw.
⁵ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: ljw33db@cgmh.org.tw.
⁶ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: 8902014@cgmh.org.tw.
⁷ Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Guishan District, Taoyuan City 33302, Taiwan. Electronic address: seanscwang@cgmh.org.tw.
⁸ Department of Physical Medicine and Rehabilitation, New Taipei Municipal, Tucheng Hospital, Chang Gung Memorial Hospital, New Taipei City 236, Taiwan; Department of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan; College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan. Electronic address: mr7171@cgmh.org.tw.
⁹ Division of Thoracic Medicine, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Chang Gung Medical Foundation, New Taipei City, Taiwan. Electronic address: shihow@cgmh.org.tw.
¹⁰ Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, Chang Gung Medical Foundation, New Taipei City 236, Taiwan. Electronic address: biology42@cgmh.org.tw.
¹¹ College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan City 33302, Taiwan. Electronic address: kuochenwei@cgmh.org.tw.
¹² College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan County 333, Taiwan; Division of Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu 300193, Taiwan. Electronic address: d000014691@cgu.edu.tw.

PMID: 41076847
DOI: 10.1016/j.jiph.2025.102989

Abstract

Background: The durability of anti-SARS-CoV-2 antibodies after vaccination or infection varies among individuals, and the role of biological aging remains unclear. This study investigated the impact of PhenoAge acceleration on antibody responses and the risk of breakthrough infection.

Methods: We analyzed serum concentration of antibodies against the receptor-binding domain of the SARS-CoV-2 S protein and calculated PhenoAge/PhenoAgeAccel using nine clinical biomarkers in 93 participants, including COVID-19-infected and vaccinated individuals, with follow-up every 3 months.

Results: Receiving ≥ 3 vaccine doses was associated with high antibody levels (OR: 4.36, p = 0.001), but natural infection was the strongest predictor (OR: 124.79, p < 0.001). Antibody titers > 2500 IU/mL protected against breakthrough infection (HR: 0.04, p = 0.0368). Despite ≥ 3 vaccine doses, individuals with titers ≤ 2500 IU/mL had increased risk (HR: 34.25, p = 0.0155). PhenoAge acceleration was associated with higher infection risk (HR: 4.75, p = 0.042).

Conclusion: Booster vaccination and natural infection are key to sustaining high antibody levels. Accelerated biological aging may increase infection risk. High antibody levels are essential to prevent breakthrough SARS-CoV-2 infection, and vaccine doses alone are insufficient without an adequate antibody response.

Keywords: Antibody titer decay; COVID-19; PhenoAge acceleration; Vaccination.

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Declaration of Competing Interest The authors do not have any conflicts of interest.

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PhenoAge acceleration predicts antibody persistence and breakthrough infection after SARS-CoV-2 vaccination and infection

Affiliations

PhenoAge acceleration predicts antibody persistence and breakthrough infection after SARS-CoV-2 vaccination and infection

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources

Miscellaneous