Short telomeres increase the risk of severe COVID-19 Aging (Albany NY) 2020 (in press)
Antoine Froidure1,2,#, Manon Mahieu3,#, Delphine Hoton4,2, Pierre-François Laterre5,2, Jean Cyr Yombi6,2, Sandra Koenig1, Benoit Ghaye7,2, Jean-Philippe Defour8,3$, Anabelle Decottignies3$ on behalf of the TELECOVID investigators*#: co-first authors $: co-senior authors
1: Department of Pulmonology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium 2: Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium 3: de Duve Institute, Université catholique de Louvain, Brussels, Belgium 4: Department of Pathology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCL), Brussels, Belgium 5: Department of Intensive Care, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium 6: Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium 7: Department of Radiology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCL), Brussels, Belgium 8: Department of Laboratory Hematology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain (UCL), Brussels, Belgium
Telomeres are non-coding DNA sequences that protect chromosome ends and shorten with age. Short telomere length (TL) is associated with chronic diseases and immunosenescence. The main risk factor for mortality of coronavirus disease 2019 (COVID-19) is older age, but outcome is very heterogeneous among individuals of the same age group. Therefore, we hypothesized that TL influences COVID-19-related outcomes.
In a prospective study, we measured TL by Flow-FISH in 70 hospitalized COVID-19 patients and compared TL distribution with our reference cohort of 491 healthy volunteers. We also correlated TL with baseline clinical and biological parameters. We stained autopsy lung tissue from six non-survivor COVID-19 patients to detect senescence-associated β-galactosidase activity, a marker of cellular aging.
We found a significantly higher proportion of patients with short telomeres (<10th percentile) in the COVID-19 patients as compared to the reference cohort (P<0.001). Short telomeres were associated with a higher risk of critical disease, defined as admission to intensive care unit (ICU) or death without ICU. TL was negatively correlated with C-reactive protein and neutrophil-to-lymphocyte ratio. Finally, lung tissue from patients with very short telomeres exhibit signs of senescence in structural and immune cells.
Our results suggest that TL influences the severity of the disease.
