Short telomeres and severe COVID-19

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Discussion Overview

The discussion centers on the relationship between telomere length and the severity of COVID-19, exploring potential mechanisms and genetic implications. Participants examine the role of telomeres in immune system function, particularly in the context of T-cell responses during SARS-CoV-2 infection.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • Some participants propose that shorter telomeres may predispose individuals to severe COVID-19, as indicated by studies measuring telomere length prior to infection.
  • Others argue that a threshold effect may exist, where telomere length impacts COVID-19 severity only after a certain age, particularly after the sixth decade of life.
  • It is suggested that genes related to immune function may be located near telomeres, potentially linking telomere length to immune system efficacy.
  • Some participants discuss the role of telomerase in T-cell clonal expansion, noting that older adults may have diminished T-cell responses due to shorter telomeres.
  • There is mention of the potential protective effect of telomere shortening against cancer, raising questions about the trade-offs associated with telomere length.

Areas of Agreement / Disagreement

Participants express multiple competing views regarding the implications of telomere length on COVID-19 severity and the underlying mechanisms, indicating that the discussion remains unresolved.

Contextual Notes

Participants note the complexity of telomere biology and its interaction with immune response, highlighting that assumptions about telomere function and genetic implications are still under investigation.

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TL;DR
Short telomeres and severe COVID-19
Not the numerical age directly, but the length of the telomeres seems to decide, if one gets severe COVID-19.

paper said:
Wang's study, in contrast, consists of 6,775 adults with COVID-19. The study's importance, however, rests not in its size but in the fact that hematopoietic cell telomere length (TL) measurements had been performed years before the SARS-CoV-2 pandemic. This critical fact means that short hematopoietic cell TL, as expressed in leukocyte TL (LTL), preceded the onset of severe COVID-19– a conclusion that excludes reverse causality, namely, that SARS-CoV-2 infection shortens LTL.
...
Sette and Crotty have recently suggested that a poor T-cell response in patients with COVID-19 leaves the innate immune response relatively unchecked, which might result in hyper-inflammation in the form of a cytokine storm and severe lung injury.
...
The TL-COVID-19 link might thus be defined by a TL “threshold”, such that TL minimally affects the course of COVID-19 until reaching this threshold. Once this threshold is crossed, largely after the sixth decade, short T-cell TL might have an amplifying, age-dependent effect on COVID-19 severity.
Source:
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00306-6/fulltext

see also:
Paternal age is positively linked to telomere length of children
Source:
https://pubmed.ncbi.nlm.nih.gov/15771613/
 
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If there is a loss of immune system function correlated with reduced telomere length, then there should be genes affecting some kind of immune system functioning, located on the chromosomes, near the telomeres (chromosome ends).
Telomere loss is often assumed to produce its negative effects by removing (or affecting the expression of) sequences, near the ends of the chromosome.

This would seem to indicate that genes for some immune function, should be located in telomeric regions of the chromosomes. This is the human genome, you should be able to look it up somewhere.
It sounds like a kind of genetic screen for mutations, where chunks of a chromosome are systematically deleted and a particular phenotype is checked for mutant effects, except it is limited to the ends of the chromosomes. People do this in Drosophila, for example.
 
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BillTre said:
If there is a loss of immune system function correlated with reduced telomere length, then there should be genes affecting some kind of immune system functioning, located on the chromosomes, near the telomeres (chromosome ends).

The reason for loss of immune system function is described here:

paper said:
Telomerase, the reverse transcriptase that elongates telomeres, is activated during T-cell clonal expansion and differentiation, but the activity of the enzyme is insufficient to counter telomere shortening with T-cell replication. T-cell replication is thus TL-dependent. As hematopoietic cell TL shorten with age, T-cells from older adults have diminished clonal expansion capacity compared to young adults. For most healthy adults, such age-dependent T-cell TL shortening might not be a major problem in absence of an acute infection, because the long half-lives of ~ 5 years of naïve cells and ~ 5 months of memory T cells in the circulation impose minimal demand on the clonal expansion capacity of T-cells. However, a massive and rapid T-cell clonal expansion might be needed after contracting SARS-CoV-2 infection.
Source:
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00306-6/fulltext
 
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BillTre said:
It sounds like a kind of genetic screen for mutations, where chunks of a chromosome are systematically deleted and a particular phenotype is checked for mutant effects, except it is limited to the ends of the chromosomes. People do this in Drosophila, for example.
Short telomeres have also an advantage:
Telomere shortening protects against cancer
...
“The data show that if you’re born with long telomeres, you are at greater risk of getting cancer, ” says de Lange.
Source:
https://www.rockefeller.edu/news/29625-telomere-shortening-protects-cancer/
 
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