The Nexus Between Telomere Length and Lymphocyte Count in Seniors Hospitalized With COVID-19

Athanase Benetos, Tsung-Po Lai, Simon Toupance, Carlos Labat, Simon Verhulst, Sylvie Gautier, Marie-Noelle Ungeheuer, Christine Perret-Guillaume, Daniel Levy, Ezra Susser, Abraham Aviv, Athanase Benetos, Tsung-Po Lai, Simon Toupance, Carlos Labat, Simon Verhulst, Sylvie Gautier, Marie-Noelle Ungeheuer, Christine Perret-Guillaume, Daniel Levy, Ezra Susser, Abraham Aviv

Abstract

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.

Keywords: COVID-19; Lymphocytes; Telomeres.

© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.

Figures

Figure 1.
Figure 1.
Lymphocyte count in relation to TeSLA telomere length parameters. Proportion of telomeres A) and non-COVID-19 patients (B) and mean telomere length by TeSLA (TeSLA mTL) in COVID-19 patients (C) and non-COVID-19 patients (D). See Supplementary Table S2 for the statistical models.
Figure 2.
Figure 2.
Depletion and repletion of the T-cell blood pool under normal condition and during COVID-19. Under normal, “steady-state” condition (A), persons with shorter telomeres maintain their T-cell blood pool. However, in the face of SARS-CoV-2 infection (B), persons with shorter telomeres might lag in their ability to increase T-cell production (increase in the pace of the T-cell pool repletion—arrow) to match increased T-cell loss due to the infection (increase in the pace of T-cell pool depletion—arrow). This nonsteady condition would result in shrinking of the T-cell pool in proportion to the shorter telomeres. Telomeres are displayed as red caps at the ends of the chromosomes.

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