Research update: telomeres and COVID-19

Telomeres and COVID-19

Since the COVID-19 global pandemic was declared by World Health Organization in March 2020 there has been a large amount of research conducted and published. Here we examine a couple of recent studies that have been conducted into telomeres and COVID-19.

Short telomeres and COVID-19

A study conducted in Belgium, published in Aging, set out to investigate the hypothesis that telomere length influences COVID-19 related outcomes.

It became clear relatively early on in the pandemic that the main risk factor for mortality of COVID-19 is older age.

With short telomeres being associated with chronic diseases, reduced immune cell function and lung fibrosis, further investigation into the potential link between telomeres and COVID-19 outcomes was justified.

The study prospectively recruited 70 patients hospitalized in COVID-19 dedicated units between April 7 and May 27, 2020.

Leukocyte telomere length was measured using the Flow FISH technique. The hospitalized patients were found to have significantly shorter telomeres than the reference population (<10th percentile, Chi-square test, P<0.0001).

The patients were then categorized into those with short telomeres (40%, <10th percentile) and compared to those with normal telomere length (60%, ≥10th percentile).

There was a statistically significant association between short telomeres and unfavorable outcome (admission in ICU and/or death) in COVID-19 hospitalized patients. This was independent of the patient’s age.

It was also found that those with short telomeres developed critical disease faster than those with normal telomere length. A trend for higher mortality in the short telomere length group was observed, but this was not statistically significant.

As a disease that has such varied experiences and outcomes (a highly heterogenous condition), ranging from asymptomatic carriers to those hospitalized on ventilators; research that furthers the understanding of risks related to increased disease severity is invaluable.

Telomere length and lymphocyte count with COVID-19

Research published in The Journals of Gerontology: Series A, tested the hypothesis that older COVID-19 patients are at a higher risk of having telomere length-dependent lymphopenia.

T-cell lymphopenia (reduced amount of white blood cells; in this case specifically T-cells) is a documented indicator for COVID-19 severity.

As telomeres play a role in the proliferation of cells, the team hypothesized that short telomeres would affect the ability to replenish T-cells lost during acute illness with COVID-19 and result in T-cell lymphopenia.

This in turn could result in worse outcomes for patients as their ability to produce enough T-cells to fight the virus would lessen.

As telomere length decreases with age, this could contribute to the risks of more severe illness and death from COVID-19 increasing with age.

The study used the Telomeres Shortest Length Assay (TeSLA) method which yields two key metrics: the proportion of telomeres with different lengths (as a percentage) and their mean length.

In addition, they quantified mean telomere length by the terminal restriction fragments (TRF) analysis, allowing comparison with a more established accepted standard for telomere length measurements.

Among the 17 COVID-19 patients, there was a significant inverse correlation between lymphocyte count and the proportion of telomeres shorter than 2kb (P = 0.005) i.e. the lymphocyte counts decreased as the proportion of short telomeres increased.

This relationship was also significant when adjusted for age and sex. This relationship was not found in the 21 non-COVID-19 patients.

Consistent with these findings, lymphocyte count was positively correlated with TeSLA mean telomere length (P = 0.03) i.e. the lymphocyte counts increased as the mean telomere length increased in COVID-19 patients.

The correlation between lymphocyte count and TRF mean telomere length showed a similar pattern but was not statistically significant.

The findings indicate that comparatively short telomeres, as expressed in the shortest telomeres of the telomere length distribution, are associated with diminished lymphocyte count (lymphopenia) in older people with active COVID-19.

The authors concluded that given the wide variation of telomere length within the population, there will be some younger adults with telomeres shorter than much older people. This is important as these younger adults with shorter telomeres may also be more at risk of COVID-19 lymphopenia. This may be valuable to address in a follow up study.

Research is a priority for us at RepeatDx with the team always keen to explore opportunities for collaborations on future projects, including those investigating telomeres and COVID-19.

To find out more about RepeatDx and our Flow FISH technology, check out our website, here.

If you would like to reach out to the team to discuss upcoming opportunities for research, please complete our contact form – it would be great to hear from you.

Sources
Baerlocher G, M. et al. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nature Protocols. 2006;1(5):2365-76. doi: 10.1038/nprot.2006.263. PMID: 17406480.
Benetos, A. et al. The Nexus between Telomere Length and Lymphocyte Count in Seniors hospitalized with Covid-19. The Journals of Gerontology: Series A. 2021; glab026. https://doi.org/10.1093/gerona/glab026.
Froidure, A. et al. Short telomeres increase the risk of severe COVID-19. Aging. vol. 12,20 (2020): 19911-19922. https://doi:10.18632/aging.104097.
Tsilingiris, D. et al. Telomere length, epidemiology and pathogenesis of severe COVID‐19. Eur J Clin Invest. 2020. 50: e13376. https://doi.org/10.1111/eci.13376.