Telomere Length and COVID-19 Severity: A Comparative Cross-Sectional Study Across the Clinical Spectrum

<b>Background</b>: Telomere attrition has been implicated in immune function and vulnerability to infectious diseases. However, the relation between telomere length and COVID-19 severity remains unclear. <b>Methods</b>: In this cross-sectional study, patients aged 30-75 years, with confirmed SARS-CoV-2 infection, as well as age- and BMI-matched controls without COVID-19, were recruited over a period of 1 year (2021-2022) from the outpatient clinics and wards of the General Hospitals "Laiko" and "Elpis" in Athens, Greece. Telomere length, expressed as a telomere to single-copy gene (T/S) ratio, was measured in all participants using a quantitative PCR-based method. Participants' clinical, biochemical, demographic, and respiratory parameters were assessed in relation to their telomere length. <b>Results</b>: Study participants included a total of 139 individuals divided into three groups: controls (n = 34), patients with non-severe COVID-19 (n = 50), and patients with severe COVID-19 (n = 55). Patients with severe COVID-19 had significantly shorter telomeres when compared to both the non-severe COVID-19 group and controls (<i>p</i> < 0.001). Logistic regression analysis confirmed that telomere length was independently associated with disease severity (<i>p</i> < 0.001). Females demonstrated longer telomeres than males (<i>p</i> = 0.039), but no significant correlation was found between telomere length and age. When patients with non-severe and severe COVID-19 were analyzed together, no significant difference in telomere length was observed compared to controls (<i>p</i> = 0.727). <b>Conclusions</b>: Shortened telomeres may be linked to more severe forms of COVID-19, suggesting a potential role for telomere biology in disease progression. Results highlight the need for further research into telomere dynamics as a biomarker for disease susceptibility and outcome in viral infections.