Association of relative telomere length with glucocorticoid therapy in critically ill patients with severe COVID-19: a preliminary study

Glucocorticoids have proven clinical benefits in reducing mortality by mitigating the systemic inflammatory response in severe COVID-19. Relative telomere length 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 glucocorticoids or stress are strongly associated with telomere shortening. This study aimed to explore the association of longitudinal relative telomere length changes with glucocorticoid therapy parameters. A prospective observational cohort study involving patients over 18 years of age with severe SARS-CoV-2 pneumonia was designed. Patients were admitted to the intensive care unit of a university hospital. Glucocorticoid therapy was standardized to dexamethasone equivalent doses based on the RECOVERY study. Blood samples were obtained upon admission and at a follow-up visit one year after discharge to determine telomere length using the Cawthon method (qPCR). Relative telomere length ratio (one year/baseline relative telomere length) associations with glucocorticoids were calculated using generalized linear models. Out of 60 patients initially screened, 49 survivors completed follow-up. A significant association was found between relative telomere length ratios and the duration of glucocorticoid therapy (aAMR = 0.98, 95% CI: 0.97–0.99; p = 0.007). The cumulative dexamethasone equivalent dose also showed a significant association with relative telomere length ratios (aAMR = 0.99, 95% CI: 0.98–0.99; p = 0.028) in the male patient subgroup (duration of therapy: aAMR = 0.98, 95% CI: 0.97–0.99, p = 0.001). No statistically significant associations were observed in female patients. In critically ill male patients with SARS-CoV-2 pneumonia, this study reveals an exploratory statistical association between relative telomere length ratio trajectories, the duration of glucocorticoid therapy, and the equivalent dose of dexamethasone. However, sex-specific differences remain exploratory. Given the limited sample size, potential survivorship bias, and residual confounding by clinical severity, these findings are hypothesis-generating. Further studies are needed to determine whether glucocorticoid exposure is associated with longitudinal RTL changes in patients admitted to the ICU for other critical conditions.