Epigenetic Age Acceleration in Surviving versus Deceased COVID-19 Patients with Acute Respiratory Distress Syndrome following Hospitalization

Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in a variety of tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS) has not been well investigated. In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiples time-points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion vs end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased vs recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID19 patients between inclusion and end of follow-up as well as a significant change in dynamic telomere attrition acceleration when comparing patients who recovered vs those who died. In conclusion, EAA and telomere attrition acceleration was associated with treatment outcome in hospitalized COVID-19 Patients with ARDS. A better understanding of the long-term effects of EAA in COVID19 patients and how they might contribute to Long COVID symptoms in recovered individuals is urgently needed.