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

Authors: James J. Anderson, Ezra Susser, Konstantin G. Arbeev, Anatoliy I. Yashin, Daniel Levy, Simon Verhulst, Abraham Aviv
Published: 04/01/2022


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.


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.


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.


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.

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