Biological age acceleration and telomere 2 shortening in COVID-19 survivors

 Alessia Mongelli,  

View ORCID Profilecarlo gaetano, michela gottardi zamperla,  View ORCID Profileveronica barbi,  View ORCID Profilesandra atlante,  View ORCID Profilemaria teresa la rovere,  View ORCID Profiletiziana bachetti,  View ORCID Profileoronzo catalano,  View ORCID Profilemaurizio bussotti, laura della vecchia,  View ORCID Profilesimona nanni,  View ORCID Profileantonella farsetti,  View ORCID Profilefabio martelli

doi: https://doi.org/10.1101/2021.04.23.21255973

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1.full.pdf

Abstract

Introduction & Background: the SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis,inflammatory cytokines release, and immunodepression. 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 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 DPP4 receptor expression were determined. The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 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 DS 2,39 Kb vs. COVID19-free: 10,67 DS 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 younger (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, they might 46 indicate a direction to investigate the pathophysiological basis of the post-COVID19 syndrome

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Ethical commettee ICS Maugeri document ID: 2543 CE

https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1