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Age-dependent decrease of circulating T follicular helper cells correlates with disease severity in elderly patients

Yihan Wang¹, Qiu Wang², Furong He¹

¹Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Tianjin 300070, China.

Clinical Immunology (Orlando, Fla.)

|July 27, 2024

Summary

Aging significantly increases COVID-19 severity by depleting crucial T follicular helper (Tfh) cells and T follicular regulatory cells (Tfr). Vaccination rejuvenates these cells, enhancing antibody production and improving outcomes in the elderly.

Keywords:

Aging COVID-19 Circulating T follicular helper cells Elderly patients Lymphopenia Vaccination

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Area of Science:

Immunology
Gerontology
Virology

Background:

Aging is a major risk factor for severe COVID-19.
Specific T cell subset changes with age and their role in COVID-19 severity need clarification.

Purpose of the Study:

To investigate age-dependent T cell subset alterations in elderly COVID-19 patients.
To assess the impact of these subsets on disease severity and antibody production.
To evaluate the effect of SARS-CoV-2 vaccination on these immune cells and responses.

Main Methods:

Recruited 57 elderly COVID-19 patients and 27 convalescent donors.
Assessed adaptive immunity across the COVID-19 severity spectrum.
Analyzed circulating T follicular regulatory cell (cTfh) subsets and circulating T follicular regulatory cells (cTfr) proportions.

Main Results:

Elderly patients showed age-dependent CD4+ T lymphopenia and loss of various cTfh subsets (cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17) and cTfr.
These cTfh and cTfr subsets correlated with COVID-19 severity.
Vaccination improved cTfh-cm, cTfh2, cTfr proportions and enhanced neutralizing antibody (NAb) production.

Conclusions:

Age-dependent deficiency in cTfh subsets and cTfr impairs NAb production, worsening COVID-19 severity in the elderly.
SARS-CoV-2 vaccination rejuvenates cTfh and cTfr cells, intensifying NAb responses and mitigating disease severity.