EVIDENCE FOR BIOLOGICAL AGE ACCELERATION AND TELOMERE SHORTENING IN COVID19 SURVIVORS

Abstract

ABSTRACT Introduction & Background the SARS-CoV-2 infection determines the COVID19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokines release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID19 syndrome (PPCS) is a common finding. In patients who survived the SARS-CoV-2 infection, overt PPCS presents one or more symptoms such as fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. The pathophysiology of PPCS is currently poorly understood, and whether epigenetic mechanisms are involved in this process is unexplored. Methods & Results In this study, a cohort of 117 COVID19 survivors (post-COVID19) and 144 non-infected volunteers (COVID19-free) were analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. Besides, telomere length (TL) and ACE2 and DPP-4 receptor expression were determined. The results show a consistent biological age increase in the post-COVID19 population (58,44 ± 14,66 ChronoAge Vs. 67,18 ± 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 ± 7,29 years (+5.25 years above range of normality) compared to 3,68 ± 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 ± 2,39 Kb vs. COVID19-free: 10,67 ± 11,69 Kb; P<0,0001). Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change. Conclusion In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID19 condition, particularly in the youngers (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, this finding might help indicating a direction to investigate the pathophysiology at the onset of the persistent post-COVID19 syndrome.