Telomere length in COVID-19: Biological aging and susceptibility to severe disease

Concept

COVID-19 is are characterized by acute lung inflammatory disease and a strong systemic inflammatory response, termed “cytokine storm” that partially resembles other situations such as macrophage activation and autoinflammatory syndromes or CART therapy. The project investigates on the hypothesis that biological ageing and TS may be mechanistically linked to hyperinflammatory responses, and propose to investigate telomere shortening (TS) as a risk factor for severe disease and for long-term morbidity after recovery from acute COVID-19.

Facts and Figures

Project Lead
J L Pablos
Hospital 12 de Octubre
jlpablos@h12o.es
FOREUM research grant: € 75.000
2021–2022

Meet the Team

Project Lead

J L Pablos
Hospital 12 de Octubre
jlpablos@h12o.es
M Galindo
Hospital 12 de Octubre
R Garcia
Hospital 12 de Octubre
E Paz
Hospital 12 de Octubre
R Perona
Hospital 12 de Octubre
L Sastre
Hospital 12 de Octubre

Final Results

We analysed telomere length (TL) by qPCR in 251 patients hospitalized for COVID-19 in the first months of the pandemics and in an age matched healthy cohort (n = 169). After discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a group of 63 patients 1 year later and compared with baseline TL.

Hospitalized COVID-19 patients had a decreased age-adjusted TL compared to the reference group. No differences in TL were observed in patients with different COVID-19 outcomes). In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated with shorter TL. Persistence of lung radiographic abnormalities was associated with shorter TL. In patients with a second TL determination, further telomere shortening was observed in 35%, and these patients had suffered a more severe disease.

Shorter TL is associated with COVID-19 hospitalization and delayed resolution of lung involvement.

Lay Summary

Aging is an important contributor to the development and progression of numerous inflammatory diseases such as rheumatic, vascular and infectious diseases. During the COVID pandemic it was observed that age was the most important factor of poor prognosis, such that older patients more frequently suffered a more severe disease characterized by greater pulmonary and systemic inflammation, and complications that led to higher mortality.

The degree of biological aging depends on chronological age but also on multiple factors such as healthy habits, previous diseases etc. Biological aging can be measured indirectly by measuring in blood cells the shortening of the terminal ends of the chromosomes called telomeres, which occurs parallel to cellular aging. It is thought that biological age has a greater influence on health or disease than chronological age.

To better understand the relationship between biological age and the severity of inflammation, we analyzed the length of telomeres in relation to the different evolution of hospitalized COVID-19 patients, and with other clinical characteristics such as the degree of inflammation, or delayed resolution of persistent symptoms or lung lesions.

The results confirmed a relationship between telomere shortening (older biological age) and the need for hospitalization for COVID. However, once hospitalized, the patients did not evolve more seriously in relation to this factor, but rather in relation to chronological age and other factors. We also observed a relationship between telomere shortening and a slower resolution of lung inflammation.

These observations support a relationship between age, biological aging, and inflammatory disease more complex than expected, which deserves further studies to better interpret its involvement in different forms of inflammatory disease.

Publications

  • Retuerto M, Lledó A, Fernandez-Varas B, Guerrero-López R, Usategui A, Lalueza A, García-García R, Mancebo E, Paz-Artal E, Sastre L, Perona R, Pablos JL. Shorter telomere length is associated with COVID-19 hospitalization and with persistence of radiographic lung abnormalities. Immun Ageing. 2022 Aug 22;19(1):38. doi: 10.1186/s12979-022-00294-9. PMID: 35996190; PMCID: PMC9394033.
    Read more

Project Map