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

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  • Additional Information
    • Source:
      Publisher: published on behalf of the Gerontological Society of America by Oxford University Press Country of Publication: United States NLM ID: 9502837 Publication Model: Print Cited Medium: Internet ISSN: 1758-535X (Electronic) Linking ISSN: 10795006 NLM ISO Abbreviation: J Gerontol A Biol Sci Med Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : published on behalf of the Gerontological Society of America by Oxford University Press
      Original Publication: Washington, DC : Gerontological Society of America, c1995-
    • Subject Terms:
      Hospitalization* ; Lymphocyte Count* ; Lymphopenia*/etiology ; Lymphopenia*/pathology; COVID-19/*physiopathology ; Telomere Shortening/*physiology; Aged, 80 and over ; Cellular Senescence ; Humans ; SARS-CoV-2/pathogenicity ; T-Lymphocytes/immunology
    • 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.
      (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)
    • Comments:
      Update of: medRxiv. 2020 Oct 04;:. (PMID: 33024983)
    • References:
      JAMA. 2003 Jun 4;289(21):2801-9. (PMID: 12734147)
      JAMA Netw Open. 2020 Jun 1;3(6):e2010895. (PMID: 32492165)
      Nat Protoc. 2010 Sep;5(9):1596-607. (PMID: 21085125)
      Cell Immunol. 2019 Nov;345:103989. (PMID: 31558266)
      Pediatrics. 2016 Apr;137(4):. (PMID: 26969272)
      J Exp Med. 2020 Oct 5;217(10):. (PMID: 32910820)
      Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6115-20. (PMID: 18420820)
      Nat Rev Immunol. 2020 Aug;20(8):499-506. (PMID: 32493982)
      J Infect. 2016 Nov;73(5):468-475. (PMID: 27519621)
      Nucleic Acids Res. 2013 Jul;41(13):e131. (PMID: 23671336)
      Nat Rev Immunol. 2020 Jun;20(6):363-374. (PMID: 32346093)
      Mol Biol Cell. 2004 Aug;15(8):3709-18. (PMID: 15181152)
      Nat Rev Immunol. 2002 Sep;2(9):699-706. (PMID: 12209138)
      JAMA Pediatr. 2020 Oct 1;174(10):e202430. (PMID: 32492092)
      Exp Hematol. 2010 Oct;38(10):854-9. (PMID: 20600576)
      Int J Infect Dis. 2020 Jul;96:131-135. (PMID: 32376308)
      Nat Rev Immunol. 2020 Sep;20(9):529-536. (PMID: 32728222)
      J Med Genet. 2015 May;52(5):297-302. (PMID: 25770094)
      FASEB J. 2020 Jun;34(6):7247-7252. (PMID: 32427393)
      J Gerontol A Biol Sci Med Sci. 2009 Sep;64(9):965-7. (PMID: 19435952)
      J Clin Invest. 2018 Dec 3;128(12):5222-5234. (PMID: 30179220)
      Cell. 2001 Oct 5;107(1):67-77. (PMID: 11595186)
      Front Immunol. 2020 May 01;11:827. (PMID: 32425950)
      Nat Commun. 2013;4:1597. (PMID: 23511462)
      Nat Commun. 2017 Nov 7;8(1):1356. (PMID: 29116081)
      Philos Trans R Soc Lond B Biol Sci. 2018 Mar 5;373(1741):. (PMID: 29335375)
      J Med Virol. 2021 Jan;93(1):234-240. (PMID: 32558955)
      Aging (Albany NY). 2017 Apr;9(4):1130-1142. (PMID: 28394764)
      Immunity. 2018 Feb 20;48(2):202-213. (PMID: 29466753)
    • Grant Information:
      U01 AG066529 United States AG NIA NIH HHS; R01HL134840 United States NH NIH HHS
    • Contributed Indexing:
      Keywords: COVID-19; Lymphocytes; Telomeres
    • Molecular Sequence:
      ClinicalTrials.gov NCT04325646
    • Publication Date:
      Date Created: 20210202 Date Completed: 20210729 Latest Revision: 20240216
    • Publication Date:
      20240216
    • Accession Number:
      PMC7929343
    • Accession Number:
      10.1093/gerona/glab026
    • Accession Number:
      33528568