Association of Relative Telomere Length with Glucocorticoids Therapy in Critically Ill Patients with COVID-19

Background: Glucocorticoids (GCs) have proven to be a key therapy in mitigating the systemic inflammatory response in severe COVID-19. Relative telomere length (RTL) is recognized as a biomarker of cellular aging and biological stress, with its role in acute critical illnesses being of growing interest. Chronic exposure to GCs or stress are strongly associated with telomere shortening. This study aimed to explore the association of RTL ratios with GCs therapy. Methods: A prospective, longitudinal study involving patients over 18 years of age with severe SARS-CoV-2 pneumonia was designed. Patients were admitted to the ICU of a university hospital. GCs therapy was standardized to dexamethasone equivalent doses based on the RECOVERY study. Blood samples were obtained upon admission and at least one year after discharge to determine telomere length using the Cawthon method (qPCR). RTL ratio (one year/baseline RTL) associations with GCs were calculated using generalized linear models (GLM). Results: A significant association was found between RTL ratios and the duration of GCs therapy (p=0.007). The dexamethasone equivalent dose also showed a significant association with RTL ratios (p<0.001). These associations were particularly significant in the male population (dexamethasone equivalent: p=0.028; duration of therapy: p=0.001), with no significant associations observed in women. Conclusion: In critically ill patients with SARS-CoV-2 pneumonia, this study reveals a significant association between RTL, the length of GCs therapy, and the equivalent dose of dexamethasone, especially in males. Further studies are needed to determine the effect of GCs on RTL admitted to de ICU for other critical conditions.