Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect

  

View ORCID ProfileJames J Anderson,  View ORCID ProfileEzra Susser,  View ORCID ProfileKonstantin G Arbeev,  View ORCID ProfileAnatoliy I Yashin,  View ORCID ProfileDaniel Levy,  View ORCID ProfileSimon Verhulst,  View ORCID ProfileAbraham Aviv

doi: https://doi.org/10.1101/2021.05.19.21257474

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.05.19.21257474v1.full.pdf

Abstract

Transient lymphopenia is a common feature of acute viral respiratory infections. The drastic and prolonged lymphopenia of COVID-19, however, is distinctive and largely stems from falling counts of T cells. This T-cell lymphopenia may contribute to the inordinate rise in COVID-19 mortality with older age, because naive T-cell clonal expansion is telomere length (TL)-dependent and TL of hematopoietic cells shortens with age. Here we present a biologically plausible model that links naive T-cell clonal expansion capacity and age-dependent hematopoietic cell TL (HCTL) shortening to explain the T- cell shortfall and the high COVID-19 mortality in older adults. The model shows that an individual with average HCTL at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next eight years. The collapse coincides with the steep increase in COVID-19 mortality with age. As young adults tend to maintain their relative HCTL over their life course, individuals with above and below average HCTL respectively experience the drop in maximal T-cell clonal expansion capacity at older and younger ages. HCTL metrics may thus explain the vulnerability of older adults to COVID-19 and predict the capacity for T-cell clonal expansion following vaccination against the virus.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

AIY and KGA research is supported by NIH grant RF1AG046860. SV human telomere research is funded NIH grant 5U24AG066528. AA telomere research is supported by NIH grants R01 HL134840, U01AG066529 and a grant from the Norwegian Research Council (NFR) ES562296.

https://www.medrxiv.org/content/10.1101/2021.05.19.21257474v1