Epigenetic Age Acceleration in Hospitalized COVID-19 Patients

The COVID-19 pandemic caused a major public health crisis and is still prevalent globally. Advanced age is one of the significant risk factors for severe COVID-19. Epigenetic alterations and telomere attrition are some of the molecular hallmarks that define aging. Epigenetic clocks are tools used to measure biological age; therefore, these clocks are utilized to measure accelerated epigenetic aging. Accelerated biological age and telomere attrition acceleration following SARS-CoV-2 have been reported by recent studies. However, accelerated epigenetic aging in hospitalized COVID-19 patients with acute respiratory distress syndrome (ARDS) and the effect on outcome (death/recovery) is not well investigated. This study included 87 severe COVID-19 patients under mechanical ventilation. The Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge epigenetic clocks were used to measure epigenetic age and the surrogate DNAm TL estimator to measure telomere length. Furthermore, the dynamic changes in epigenetic aging across several time points until patient recovery or death were analysed.

The results of the study revealed significant accelerated epigenetic aging (EAA) in severe cases, however, no significant telomere attrition acceleration was observed. Furthermore, in certain clocks, epigenetic deceleration was detected when comparing patients at inclusion versus the end of follow-up in the recovered cases. In addition, higher EAA using Horvath and PhenoAge clocks was observed when analyzing dynamic changes in epigenetic aging of the deceased versus recovered patients. Finally, telomere attrition acceleration was revealed in deceased patients between inclusion and the end of follow-up. The results demonstrate how epigenetic age acceleration and telomere attrition are linked with severe COVID-19 outcomes in hospitalized patients with ARDS. Therefore, a better understanding of accelerated aging in COVID-19 patients is essential for the treatment and management of the disease.