Elsevier

eBioMedicine

Volume 78, April 2022, 103978
eBioMedicine

Articles
Telomere-length dependent T-cell clonal expansion: A model linking ageing to COVID-19 T-cell lymphopenia and mortality

https://doi.org/10.1016/j.ebiom.2022.103978Get rights and content
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Summary

Background

Severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent.

Methods

We developed a model of TL-dependent T-cell clonal expansion capacity with age and virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population.

Findings

The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity rapidly declines by more than 90% over the next ten years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in COVID-19 mortality with age.

Interpretation

Short HCTL might increase vulnerability of many older adults, and some younger individuals with inherently short HCTL, to COVID-19 T-cell lymphopenia and severe disease.

Funding

A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Keywords

Telomeres
T-cells
COVID-19
SARS-CoV-2
Ageing
Vaccines

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Disclaimer: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.